Publications by authors named "Zhen Huang"

823 Publications

N95 respirator reuse, decontamination methods, and microbial burden: A randomized controlled trial.

Am J Otolaryngol 2021 Mar 31;42(5):103017. Epub 2021 Mar 31.

Department of Otorhinolaryngology-Head and Neck Surgery, McGovern Medical School, Houston, TX, USA; Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine, McGovern Medical School at The University of Texas Health Science Center, Houston, TX, USA. Electronic address:

Purpose: To evaluate the effectiveness and ease of N95 respirator decontamination methods in a clinic setting and to identify the extent of microbial colonization on respirators associated with reuse.

Methods: In a prospective fashion, N95 respirators (n = 15) were randomized to a decontamination process (time, dry heat, or ultraviolet C light [UVC]) in outpatient clinics. Each respirator was re-used up to 5 separate clinic sessions. Swabs on each respirator for SARS-CoV-2, bacteria, and fungi were obtained before clinic, after clinic and post-treatment. Mask integrity was checked after each treatment (n = 68). Statistical analyses were performed to determine factors for positive samples.

Results: All three decontamination processes reduced bacteria counts similarly. On multivariate mixed model analysis, there were an additional 8.1 colonies of bacteria (95% CI 5.7 to 10.5; p < 0.01) on the inside compared to the outside surface of the respirators. Treatment resulted in a decrease of bacterial load by 8.6 colonies (95% CI -11.6 to -5.5; p < 0.01). Although no decontamination treatment affected the respirator filtration efficiency, heat treatments were associated with the breakdown of thermoplastic elastomer straps. Contamination with fungal and SARS-CoV-2 viral particles were minimal to non-existent.

Conclusions: Time, heat and UVC all reduced bacterial load on reused N95 respirators. Fungal contamination was minimal. Heat could permanently damage some elastic straps making the respirators nonfunctional. Given its effectiveness against microbes, lack of damage to re-treated respirators and logistical ease, UVC represents an optimal decontamination method for individual N95 respirators when reuse is necessary.
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http://dx.doi.org/10.1016/j.amjoto.2021.103017DOI Listing
March 2021

True cost of surgical aortic valve replacement and implications for price setting and diagnosis-related groups: evidence from a tertiary hospital in Eastern China.

J Comp Eff Res 2021 Apr 15. Epub 2021 Apr 15.

The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310002, China.

Surgical aortic valve replacement (SAVR) has long been the standard treatment for patients with severe aortic stenosis in China, but the costs of SAVR from a hospital perspective in China have not been thoroughly researched. Currently, diagnosis-related groups in China are based on historical expenses that are closely related to the unit charges set by the official pricing department and are frequently inaccurate compared with actual resource consumption. Through a retrospective empirical study on the costs and charges of SAVR cases in a tertiary hospital, this study aimed to compare the costs and charges of service items. We collected clinical information from patients undergoing SAVR (isolated or concomitant procedures) and financial information from the hospital in 2015 and 2016. Top-down full cost accounting and step-allocation were the main methods used in this study. This research selected 203 SAVR cases in 2015 and 214 cases in 2016. The median length of hospital stay was 15.92 days (6.07 days pre surgery and 9.57 days post surgery). The average human resource cost of care per day per bed in the cardiovascular surgery department, including doctors and nurses, was US $62.22 in 2015 and $66.17 in 2016, but the corresponding charge was no more than $24. For operation, the cost of isolated SAVR was $665 in 2015 and $1015 in 2016, while the charge was $820. For anesthesiology, the cost of isolated SAVR was $400 in 2015 and $526 in 2016, while the average charge was $192. For examination service items, some costs did not exceed charges. The average total cost of a case was $19,299 ± 8954, while the average total charge was $18,923 ± 9194. SAVR is associated with significant resource utilization and hospital stay duration. The fees for human resources and services associated with SAVR do not reflect the true costs of SAVR in a Chinese hospital setting. This study may assist in future budget planning and price setting for policy makers in China.
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http://dx.doi.org/10.2217/cer-2021-0037DOI Listing
April 2021

CT-Guided Microcoil Localization of Small Peripheral Pulmonary Nodules to Direct Video-Assisted Thoracoscopic Resection without the Aid of Intraoperative Fluoroscopy.

Korean J Radiol 2021 Apr 1. Epub 2021 Apr 1.

Department of Radiology, China-Japan Friendship Hospital, Beijing, China.

Objective: To evaluate the feasibility, safety, and effectiveness of CT-guided microcoil localization of solitary pulmonary nodules (SPNs) for guiding video-assisted thoracoscopic surgery (VATS).

Materials And Methods: Between June 2016 and October 2019, 454 consecutive patients with 501 SPNs who received CT-guided microcoil localization before VATS in our institution were enrolled. The diameter of the nodules was 0.93 ± 0.49 cm, and the shortest distance from the nodules to the pleura was 1.41 ± 0.95 cm. The distal end of the microcoil was placed less than 1 cm away from the nodule, and the proximal end was placed outside the visceral pleura. VATS was performed under the guidance of implanted microcoils without the aid of intraoperative fluoroscopy.

Results: All 501 nodules were marked with microcoils. The time required for microcoil localization was 12.8 ± 5.2 minutes. Microcoil localization-related complications occurred in 179 cases (39.4%). None of the complications required treatment. A total of 463 nodules were successfully resected under the guidance of implanted microcoils. VATS revealed 38 patients with dislocated microcoils, of which 28 underwent wedge resection (21 cases under the guidance of the bleeding points of pleural puncture, 7 cases through palpation), 5 underwent direct lobectomy, and the remaining 5 underwent a conversion to thoracotomy. In 4 cases, a portion of the microcoil remained in the lung parenchyma.

Conclusion: CT-guided microcoil localization of SPNs is safe and reliable. Marking the nodule and pleura simultaneously with microcoils can effectively guide the resection of SPNs using VATS without the aid of intraoperative fluoroscopy.
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http://dx.doi.org/10.3348/kjr.2020.0331DOI Listing
April 2021

Nomograms incorporating preoperative RDW level for the prediction of postoperative complications and survival in colorectal liver metastases after resection.

Ann Palliat Med 2021 Apr 7. Epub 2021 Apr 7.

Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: This study aimed to investigate the predictive significance of preoperative red cell volume distribution width (RDW) level for prognosis and to establish nomograms incorporating preoperative blood markers to predict postoperative complications and survival in patients with colorectal liver metastases (CRLM).

Methods: This retrospective study included 380 enrolled CRLM patients who underwent hepatic resection. Predictors of postoperative complications were explored using binary logistic regression analysis. Covariates associated with overall survival (OS) and progression-free survival (PFS) were evaluated through univariate and multivariate Cox regression analyses. Only variables that reached statistical significance at P<0.1 in the univariate analysis were allowed to enter the multivariate analyses. The independent predictors that retained in the final multivariate model were incorporated into nomograms.

Results: The optimal cut-off point of preoperative RDW-CV was 16%, and elevated RDW-CV was significantly associated with better prognosis (mPFS: 5.0 vs. 8.9 months, P=0.007; mOS: 59.0 vs. 42.0 months, P=0.041). The optimal cut-off point of preoperative RDW-SD was 43.9 fl, and elevated RDWSD was significantly associated with worse prognosis (mPFS: 8.0 vs. 13.0 months, P<0.001; mOS:36.8 vs. 70.2 months, P=0.001). A nomogram predicting postoperative complications was constructed based on preoperative gamma-glutamyl transpeptidase (GGT) ≥34.5 U/L, preoperative RDW-CV ≥14.1%, and intraoperative blood loss ≥200.0 mL, with AUROC of 0.658. The calibration curves and HosmerLemeshow test revealed desirable model calibration (chi-square: 3.99, P=0.91). A nomogram predicting PFS was constructed based on preoperative GGT ≥31.0 U/L, preoperative D-dimer ≥0.251 mg/L, preoperative RDW-CV <16.0%, preoperative RDW-SD ≥43.9 fl, positive lymph node metastasis, bilobar liver distribution, and R0 resection with good discrimination (C-index: 0.676±0.016) and calibration. A nomogram for the prediction of OS was constructed with favorable discrimination (C-index: 0.700±0.021) and calibration. Significant differences in PFS and OS were shown among patients stratified into three different risk groups (P<0.001) based on the nomograms.

Conclusions: This study first revealed the relationship between preoperative RDW-SD, RDW-CV, and prognosis in patients with CRLM. It also established nomograms especially considering preoperative blood markers to predict postoperative complications, PFS, and OS, which facilitated physicians to determine the optimal clinical management strategies.
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http://dx.doi.org/10.21037/apm-20-2418DOI Listing
April 2021

Nomograms predicting primary lymph node metastases and prognosis for synchronous colorectal liver metastasis with simultaneous resection of colorectal cancer and liver metastases.

Ann Palliat Med 2021 Mar 23. Epub 2021 Mar 23.

Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: It is necessary to identify valuable predictors of primary lymph node metastasis and prognosis for patients with synchronous colorectal cancer liver metastases (CRLM) with simultaneous resection of colorectal cancer (CRC) and liver metastases. This study constructed nomograms especially incorporating preoperative testing markers to predict primary lymph node metastases and prognosis in CRLM patients.

Methods: By the highest Youden index (sensitivity + 1-specificity), the optimal cut-off values of testing markers for postoperative major complications and lymph node metastasis were identified. Multivariate regression analysis was used to reveal independent predictors for primary lymph node metastasis, postoperative major complications and progression-free survival (PFS). Nomograms based on independent predictors were constructed, and the discrimination and calibration were evaluated.

Results: A nomogram predicting primary lymph node metastasis was based on four risky independent predictors: American Society of Anesthesiologists (ASA) score 3-4, preoperative albumin (ALB) <41.15 g/ L, poor differentiation and multiple liver metastases. The performance of the model was acceptable in predicting lymph node metastasis, with an area under the receiver operating characteristic curve (AUROC) of 0.655 (95% CI: 0.591-0.739). Calibration curves and the Hosmer-Lemeshow test revealed desirable model calibration (chi-square: 13.26, P=0.815). In the multivariate analysis, preoperative lactate dehydrogenase (LDH) ≥202.5 U/L [odds ratio (OR) =2.084, 95% confidence interval (CI): 1.039-4.181, P=0.039] and operation time ≥350.5 min (OR =2.848, 95% CI: 1.418-5.723, P=0.003) were independently associated with the presence of postoperative major complications. A nomogram predicting PFS was constructed based on poor differentiation, positive lymph node metastasis, bilobar liver distribution and R0 resection with good discrimination (C-index: 0.656±0.021) and calibration.

Conclusions: This study established predictive nomograms specifically incorporating preoperative ALB and LDH levels for the prediction of primary lymph node metastasis and prognosis in synchronous CRLM patients with simultaneous resection, which have favourable discrimination and calibration to make individualized predictions.
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http://dx.doi.org/10.21037/apm-20-2303DOI Listing
March 2021

Harpagide exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress via SERCA following oxygen-glucose deprivation/reoxygenation injury.

Neurosci Lett 2021 Apr 1;753:135874. Epub 2021 Apr 1.

College of Pharmacy, Zhe Jiang Chinese Medical University, Hangzhou, 310053, China. Electronic address:

Cerebrovascular diseases endanger human health, and the physiological and pathological processes of cerebral ischemia/reperfusion injury (CIRI) are critical for the occurrence of these diseases and as targets for their treatment. Here, we evaluated the effects of harpagide-mediated pharmacological and genetic inhibition of sarco-endoplasmic reticulum Ca-ATPase (SERCA) in vitro in PC12 cells. The molecular mechanism by which harpagide protects PC12 cells against oxygen-glucose deprivation/reoxygenation (OGD/R) injury was investigated by evaluating the cell survival rate with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, assessing apoptosis by flow cytometry, determining the intracellular Ca concentration ([Ca]) by laser scanning confocal microscopy (LSCM), and measuring the expression of proteins related to SERCA and endoplasmic reticulum stress (ERS) by Western blotting. The results revealed that harpagide significantly decreased thapsigargin (TG)-induced apoptosis of PC12 cells, downregulated the expression of ERS-related markers, considerably improved the TG-induced expression of SERCA-related proteins and reduced the [Ca], suggesting that harpagide effectively inhibited ERS directly. Moreover, harpagide did not significantly reduce OGD/R-induced apoptosis but increased the expression of ERS markers in PC12/SERCA cells, indicating that harpagide targets SERCA to protect against CIRI by suppressing ERS-mediated apoptosis.
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http://dx.doi.org/10.1016/j.neulet.2021.135874DOI Listing
April 2021

A high-quality genome provides insights into the new taxonomic status and genomic characteristics of Cladopus chinensis (Podostemaceae).

Hortic Res 2020 Apr 1;7(1):46. Epub 2020 Apr 1.

Public Service Platform for Industrialization Development Technology of Marine Biological Medicine and Products of the State Oceanic Administration, Fujian Key Laboratory of Special Marine Bioresource Sustainable Utilization, Key Laboratory of Developmental and Neural Biology, College of Life Sciences, Fujian Normal University, Fuzhou, China.

The Podostemaceae are ecologically and morphologically unusual aquatic angiosperms that survive only in rivers with pristine hydrology and high water quality and are at a relatively high risk of extinction. The taxonomic status of Podostemaceae has always been controversial. Here, we report the first high-quality genome assembly for Cladopus chinensis of Podostemaceae, obtained by incorporating Hi-C, Illumina and PacBio sequencing. We generated an 827.92 Mb genome with a contig N50 of 1.42 Mb and 27,370 annotated protein-coding genes. The assembled genome size was close to the estimated size, and 659.42 Mb of the assembly was assigned to 29 superscaffolds (scaffold N50 21.22 Mb). A total of 59.20% repetitive sequences were identified, among which long terminal repeats (LTRs) were the most abundant class (28.97% of the genome). Genome evolution analysis suggested that the divergence time of Cladopus chinensis (106 Mya) was earlier than that of Malpighiales (82 Mya) and that this taxon diverged into an independent branch of Podestemales. A recent whole-genome duplication (WGD) event occurred 4.43 million years ago. Comparative genomic analysis revealed that the expansion and contraction of oxidative phosphorylation, photosynthesis and isoflavonoid metabolism genes in Cladopus chinensis are probably related to the genomic characteristics of this growing submerged species. Transcriptome analysis revealed that upregulated genes in the shoot group compared to the root group were enriched in the NAC gene family and transcription factors associated with shoot development and defense responses, including WUSCHEL (WUS), ASYMMETRIC LEAVES (ASL), SHOOT MERISTEMLESS (STM), NAC2, NAC8, NAC29, NAC47, NAC73, NAC83 and NAC102. These findings provide new insights into the genomic diversity of unusual aquatic angiosperms and serve as a valuable reference for the taxonomic status and unusual shoot apical meristem of Podostemaceae.
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http://dx.doi.org/10.1038/s41438-020-0269-5DOI Listing
April 2020

Chemotherapy-induced amenorrhea and its effects on fertility in long-term female survivors of classic osteosarcoma.

Support Care Cancer 2021 Mar 26. Epub 2021 Mar 26.

Bone Oncology, Beijing Jishuitan Hospital, 31 east street of Xinjiekou, Xicheng District, Beijing, China.

Purpose: To explore the effect of chemotherapy-induced amenorrhea (CIA) on female osteosarcoma patients' fertility function, we investigated and analyzed their marital status, fertility, and menstrual status in a retrospective cohort study.

Methods: We selected female osteosarcoma patients from database from January 2004 to December 2013. Patients' characteristics such as age, tumor location, marital status, menstrual status, and fertility status were collected. The data were analyzed using the Statistical Package for the Social Sciences (SPSS), version 22.

Results: A total of 122 female patients met these criteria and finally responded by questionnaire and telephone follow-up. The marriage rate of female osteosarcoma survivors was 50.8% (62/122), which was significantly lower than the control group (p = 0.000). The average marriage age of female osteosarcoma survivors was 25.5, which was obviously higher than the control group (p = 0.000). CIA occurred in 46 (36.1%) patients. We then found that the incidence of CIA was higher in older patients. (p = 0.011). All of the married patients wanted to have children, and 67.8% (42/62) of them had given birth after chemotherapy. The fertility of married patients with CIA was significantly reduced compared to that of married patients without CIA. (p = 0.001).

Conclusions: The patients with CIA have higher risk of impaired reproductive function than those who did not. Fertility preservation option before the start of the chemotherapy is important. And it is much value to record menstrual pattern and detect sex steroid levels after 6 months of therapy in order to be able to evaluate the fertility status.
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http://dx.doi.org/10.1007/s00520-021-06069-0DOI Listing
March 2021

Clinical study of diabetic peripheral neuropathy screening by retinal vascular geometric parameters.

Sci Rep 2021 Mar 24;11(1):6784. Epub 2021 Mar 24.

Department of Endocrinology, Longgang Central Hospital, Shenzhen 1228 Longgang Road, Shenzhen, 518116, Guangdong, China.

To investigate the relationship between geometrical changes of retinal vessels and diabetic peripheral neuropathy (DPN), and to determine the effectiveness of retinal vascular geometry analysis and vibration perception threshold (VPT) for DPN assessment. Type 2 diabetes patients (n = 242) were categorized by stage of DPN. VPT and fundus photography was performed to obtain retinal vascular geometry parameters. The risk factors for DPN and the correlation between DPN stages were analyzed. The efficiency of the retinal vascular geometric parameters obtained with VPT as a diagnostic tool for DPN was examined. Stages of DPN showed a linear correlation with VPT (r = 0.818), central retinal vein equivalent (CRVE) (r = 0.716), and fractal dimension arterioles (DFa) (r = - 0.769). VPT, CRVE, DFa, and fractal dimension veins (DFv) showed high sensitivity (80%, 55%, 82%, and 67%, respectively) and specificity (92%, 93%, 82%, and 80%, respectively) for DPN diagnosis. Good agreement was observed between combined use of geometric parameters (CRVE, DFa and DFv) and VPT (Kappa value 0.430). The detection rate of DPN with combined use of geometric parameters of retinal vessels (64.88%) was significantly higher than that with use of VPT (47.52%). Retinal vascular geometry changes demonstrated significant correlation with DPN severity. VPT, CRVE, DFa, and DFv may provide insights for understanding DPN.
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http://dx.doi.org/10.1038/s41598-021-85831-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990935PMC
March 2021

Integrated analysis of immune-related long noncoding RNAs as diagnostic biomarkers in psoriasis.

PeerJ 2021 8;9:e11018. Epub 2021 Mar 8.

Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Background: Psoriasis is a chronic immune-mediated inflammatory dermatosis. Long noncoding RNAs (lncRNAs) play an important role in immune-related diseases. This study aimed to identify potential immune-related lncRNA biomarkers for psoriasis.

Methods: We screened differentially expressed immune-related lncRNAs biomarkers using GSE13355 (skin biopsy samples of 180 cases) from Gene Expression Omnibus (GEO). Moreover, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were performed to explore biological mechanisms in psoriasis. In addition, we performed LASSO logistic regression to identify potential diagnostic lncRNAs and further verify the diagnostic value and relationship with drug response using two validation sets: GSE30999 (skin biopsy samples of 170 cases) and GSE106992 (skin biopsy samples of 192 cases). Furthermore, we estimated the degree of infiltrated immune cells and investigated the correlation between infiltrated immune cells and diagnostic lncRNA biomarkers.

Results: A total of 394 differentially expressed genes (DEGs) were extracted from gene expression profile. GO and KEGG analysis of target genes found that immune-related lncRNAs were primarily associated with epidermis development, skin development, collagen-containing extracellular matrix, and glycosaminoglycan binding and mainly enriched in cytokine-cytokine receptor interaction and influenza A and chemokine signaling pathway. We found that LINC01137, LINC01215, MAPKAPK5-AS1, TPT1-AS1, CARMN, CCDC18-AS1, EPB41L4A-AS, and LINC01214 exhibited well diagnostic efficacy. The ROC and ROC CI were 0.944 (0.907-0.982), 0.953 (0.919-0.987), 0.822 (0.758-0.887), 0.854 (0.797-0.911), 0.957(0.929-0.985), 0.894 (0.846-0.942), and 0.964 (0.937-0.991) for LINC01137, LINC01215, MAPKAPK5-AS1, TPT1-AS1,CARMN, CCDC18-AS1, EPB41L4A-AS1, and LINC01214. LINC01137, LINC01215, and LINC01214 were correlated with drug response. LINC01137, CCDC18-AS1, and CARMN were positively correlated with activated memory CD4 T cell, activated myeloid dendritic cell (DC), neutrophils, macrophage M1, and T follicular helper (Tfh) cells, while negatively correlated with T regulatory cell (Treg). LINC01215, MAPKAPK5-AS1, TPT1-AS1, EPB41L4A-AS, and LINC01214 were negatively correlated with activated memory CD4 T cell, activated myeloid DC, neutrophils, macrophage M1, and Tfh, while positively correlated with Treg.

Conclusions: These findings indicated that these immune-related lncRNAs may be used as potential diagnostic and predictive biomarkers for psoriasis.
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http://dx.doi.org/10.7717/peerj.11018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950217PMC
March 2021

Alternations of cesarean section rates in a non-infected population after the outbreak of COVID-19: a cross-sectional study.

Psychol Health Med 2021 Mar 15:1-7. Epub 2021 Mar 15.

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

The pandemic of Coronavirus Disease 2019(COVID-19) could be sources of anxiety among pregnant women and health care workers, which might affect the decision making on the mode of delivery. The aim of this study was to explore whether the cesarean section rates had significantly increased after the outbreak of COVID-19. We analyzed the labor data with cesarean rates in a tertiary maternity center during COVID-19 epidemic months from January to March in 2020, compared with pre-epidemic parallel months in 2019 by using Z-score test for proportions. Even though none of the staff or patient suffered with COVID-19 in the hospital, we found the cesarean section rates slightly increased in a non-infected population after the outbreak of COVID-19. Obstetricians should beware of the possible effects of COVID-19 on the mode of delivery.
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http://dx.doi.org/10.1080/13548506.2021.1893768DOI Listing
March 2021

Upgraded nomograms for the prediction of complications and survival in patients with colorectal liver metastases treated with neoadjuvant chemotherapy followed by hepatic resection.

Ann Transl Med 2021 Feb;9(3):265

Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: To establish upgraded nomograms incorporating neoadjuvant chemotherapy (NAC)-related factors and preoperative testing markers to predict postoperative complications, progression-free survival (PFS) and overall survival (OS) in patients with colorectal liver metastases (CRLM).

Methods: Multivariate regression analyses were used to reveal independent predictors for postoperative complications, PFS and OS. Nomograms incorporating independent predictors were constructed, and discrimination and calibration were evaluated. Survival was estimated by the Kaplan-Meier method and compared using the log-rank test.

Results: A nomogram predicting postoperative complications was constructed based on preoperative serum gamma-glutamyl transpeptidase (GGT) ≥36 U/L, major liver resection, intraoperative blood loss ≥300 mL, primary site located in the right hemicolon and primary lymph node metastasis, with an area under the receiver operating characteristic curve (AUROC) of 0.750. The calibration curves and Hosmer-Lemeshow test revealed desirable model calibration (chi-square: 4.47, P=0.88). Moreover, a nomogram for the prediction of PFS was constructed based on tumour regression grade (TRG), primary lymph node metastasis, R0 resection and NAC cycles ≥5, with good discrimination (C-index: 0.663±0.024) and calibration, and one for predicting OS was constructed based on preoperative GGT ≥36 U/L, NAC toxicity, NAC cycles ≥5, primary lymph node metastasis and R0 resection, with favourable discrimination (C-index: 0.684±0.030) and calibration. Significant differences in PFS and OS were observed among patients stratified into three different risk groups (P<0.001) according to total scores based on the nomograms.

Conclusions: This study is the first to establish novel predictive nomograms specifically incorporating TRG, NAC toxicity and serum GGT level for the prediction of postoperative complications, PFS and OS in CRLM patients. The nomograms exhibit favourable discrimination and calibration to guide personalized CRLM management and therapy.
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http://dx.doi.org/10.21037/atm-20-3973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940886PMC
February 2021

The prognostic factors of primary colorectal sarcoma and the clinical outcomes of negative lymph node dissection.

Ann Transl Med 2021 Feb;9(3):250

Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Primary colorectal sarcoma is an extremely rare malignancy that is associated with poor patient outcomes. The aim of this study was to identify the prognostic factors of primary colorectal sarcoma and evaluate the clinical outcomes associated with these prognostic factors.

Methods: Between January 1, 2000 and December 31, 2016, the clinical data of 315 patients with primary colorectal sarcoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Cancer-specific survival (CSS) was analyzed by the Kaplan-Meier method and by log-rank test. The prognostic factors were identified by univariate and multivariate Cox regression analysis and hazard ratio (HR) and 95% confidence interval (CI) of covariates were also estimated. The optimal cutoff value for NLN count at dissection was identified using X-tile software and validated by univariate Cox regression analysis.

Results: Of the 315 patients with primary colorectal sarcoma identified, 88.6% received surgery. The median follow-up time was 34 months with an interquartile range (IQR) of 9-79 months. The 5-year rate of CSS was 76.73% and 27.8% for the surgery group and the non-surgery group, respectively (P<0.0001). Univariate and multivariate Cox regression analysis performed on the data of nonmetastatic patients demonstrated that sex, race, radiotherapy, and chemotherapy had no effect on patient CSS, with age, tumor site, tumor grade, and NLN dissection being independent prognostic factors. A significant correlation was found between advanced age (>80 years old) and poor CSS (HR 1.964; 95% CI: 1.005-3.839; P=0.048). There were also significant correlations between colonic tumors and poor CSS (HR 2.903; 95% CI: 1.348-6.250; P=0.006) and grade IV tumors and poor CSS (HR 3.431; 95% CI: 1.725-6.823; P<0.001), while NLN dissection was associated with improved CSS (HR 0.946; 95% CI: 0.911-0.983; P=0.004). X-tile software analysis was used to determine that the optimal cutoff value for NLN count was 13. Patients who received NLN dissection with a cutoff value of 13 or more displayed better CSS than those who did not (P=0.016).

Conclusions: Primary colorectal sarcoma patients can benefit significantly from primary tumor surgery. Age, tumor site, grade and NLN dissection are independent prognostic factors for CSS in nonmetastatic patients. Importantly, nonmetastatic patients treated with NLN dissection with an NLN count of 13 or more have significantly better CSS.
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http://dx.doi.org/10.21037/atm-20-4286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940912PMC
February 2021

Motor Function Assessment of Upper Limb in Stroke Patients.

J Healthc Eng 2021 24;2021:6621950. Epub 2021 Feb 24.

School of Sports Engineering, Beijing Sport University, Beijing, China.

Background: Quantitative assessment of motor function is extremely important for poststroke patients as it can be used to develop personalized treatment strategies. This study aimed to propose an evaluation method for upper limb motor function in stroke patients.

Methods: Thirty-four stroke survivors and twenty-five age-matched healthy volunteers as the control group were recruited for this study. Inertial sensor data and surface electromyography (sEMG) signals were collected from the upper limb during voluntary upward reaching. Five features included max shoulder joint angle, peak and average speeds, torso balance calculated from inertial sensor data, and muscle synergy similarity extracted from sEMG data by the nonnegative matrix factorization algorithm. Meanwhile, the Fugl-Meyer score of each patient was graded by professional rehabilitation therapist.

Results: Statistically significant differences were observed among severe, mild-to-moderate, and control group of five features ( ≤ 0.001). The features varied as the level of upper limb motor function changes since these features significantly correlated with the Fugl-Meyer assessment scale ( ≤ 0.001). Moreover, the Bland-Altman method was conducted and showed high consistency between the evaluation method of five features and Fugl-Meyer scale. Therefore, the five features proposed in this paper can quantitatively evaluate the motor function of stroke patients which is very useful in the rehabilitation process.
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http://dx.doi.org/10.1155/2021/6621950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932780PMC
February 2021

Co-culture with Sirt1-overexpressed chondrocytes delays the nucleus pulposus cells degeneration.

Cell Tissue Bank 2021 Mar 8. Epub 2021 Mar 8.

Department of Orthopaedics, Bengbu Third People's Hospital, Shengli Road 38, Bengshan District, Bengbu, Anhui, China.

Nucleus pulposus cells (NPCs) degeneration is an essential pathological basis of intervertebral disc diseases, and autologous cell transplantation is a means of regeneration of NPCs. This study aimed to evaluate the effects of autologous facet joint chondrocytes (CHs) with Sirtuin 1 (sirt1)-overexpression on NPCs degeneration. We used human NPCs and CHs isolated from the patients' tissue and transduced CHs with the plasmid vector to overexpress the sirt1 gene. Further, NPCs were seeded as monolayers and treated with IL-1β to obtain the degeneration, and the sirt1-overexpressed CHs (sirt1-CHs) in the transwell insert were co-cultured in the same well. The NPCs' degenerated degree was determined by the levels of living cells, proliferation, p16, and collagen I/II, and aggrecan expression at the time point of 1, 3, or 5 days. Besides, the ROS accumulation, antioxidative enzymes, sirt1, and inflammatory factors gene expression were also tested. After IL-1β treatment, when co-cultured with sirt1-CHs, NPCs accumulated more living cells, proliferation, collagen II, aggrecan, but less p16 and collagen I expression than cultured without sirt1-CHs. Additionally, SOD1, CAT, and TIMP4 mRNA were protected, and the production of TNF-α, IL-6, MMP3, and ROS were alleviated with the presence of sirt1-CHs. Thus, co-culture with sirt1-CHs delays NPCs' degeneration via the suppression of ROS accumulation and inflammatory response. Transplanting autologous CHs with sirt1-overexpressed into the NP tissue might be a novel treatment for intervertebral disc degeneration.
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http://dx.doi.org/10.1007/s10561-021-09912-0DOI Listing
March 2021

Preoperatively elevated RDW-SD and RDW-CV predict favorable survival in intrahepatic cholangiocarcinoma patients after curative resection.

BMC Surg 2021 Mar 1;21(1):105. Epub 2021 Mar 1.

Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Nanli, Panjiayuan, Chaoyang District, Beijing, China.

Background: Recent studies suggest red blood cell distribution width (RDW) was a prognostic factor in various types of cancer patients, although the results are controversial. The objective of this study was to investigate the significance of RDW in patients with intrahepatic cholangiocarcinoma (ICC) after radical resection.

Method: The relationship between the preoperative serum RDW value and clinic pathological characteristics was analyzed in 157 ICC patients between January 2012 and June 2018 who underwent curative resection. X-tile software was used to determine 40.2 fl, 12.6% as the optimal cut-off value for RDW-SD and RDW-CV respectively. 153 patients were classified into the low RDW-SD (≤ 40.2, n = 53) group and the high RDW-SD (> 40.2, n = 104) group, low RDW-CV (≤ 12.6, n = 94) group and the high RDW-CV (> 12.6, n = 63). Based on the RDW-SD combined with RDW-CV (SCC), classified into SCC = 0, 1 and 2 group. Kaplan-Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival.

Results: Kaplan-Meier curve analysis showed that Patients with RDW-SD > 40.2 were significantly associated with better OS (P = 0.004, median OS: 68.0 months versus 17.0 months). Patients with RDW-CV > 12.6 were significantly associated with better OS (p = 0.030, median OS: not reach versus 22.0 months). Compared with a SCC = 0 or SCC = 1, SCC = 2 was significantly associated with better OS (p < 0.001, median OS: not reach versus 33.0 months versus 16, respectively). In the multivariate analysis, RDW-SD > 40.2 fl (HR = 0.446, 95% CI: 0.262-0.760, p = 0.003), RDW-CV > 12.6% (HR = 0.425, 95%CI: 0.230-0.783, p = 0.006), SCC = 2 (HR = 0.270, 95%CI: 0.133-0.549, p < 0.001) were associated with favorable OS. The multivariate analysis showed RDW-SD, RDW-CV and SCC level were not independent prognostic factors for DFS.

Conclusions: Preoperative low levels of RDW are associated with poor survival in ICC after curative resection. This provides a new way for predicting the prognosis of ICC patients and more targeted intervention measures.
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http://dx.doi.org/10.1186/s12893-021-01094-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919078PMC
March 2021

Insights into salvianolic acid B biosynthesis from chromosome-scale assembly of the Salvia bowleyana genome.

J Integr Plant Biol 2021 Feb 26. Epub 2021 Feb 26.

The Public Service Platform for Industrialization Development Technology of Marine Biological Medicine and Products of the State Oceanic Administration, Fujian Key Laboratory of Special Marine Bioresource Sustainable Utilization, Southern Institute of Oceanography, College of Life Sciences, Fujian Normal University, Fuzhou, 350117, China.

Salvia bowleyana is a traditional Chinese medicinal plant that is a source of nutritional supplements rich in salvianolic acid B and a potential experimental system for the exploration of salvianolic acid B biosynthesis in the Labiatae. Here, we report a high-quality chromosome-scale genome assembly of S. bowleyana covering 462.44 Mb, with a scaffold N50 value of 57.96 Mb and 44,044 annotated protein-coding genes. Evolutionary analysis revealed an estimated divergence time between S. bowleyana and its close relative S. miltiorrhiza of ~3.94 million years. We also observed evidence of a whole-genome duplication in the S. bowleyana genome. Transcriptome analysis showed that SbPAL1 (PHENYLALANINE AMMONIA-LYASE1) is highly expressed in roots relative to stem and leaves, paralleling the location of salvianolic acid B accumulation. The laccase gene family in S. bowleyana outnumbered their counterparts in both S. miltiorrhiza and Arabidopsis thaliana, suggesting that the gene family has undergone expansion in S. bowleyana. Several laccase genes were also highly expressed in roots, where their encoded proteins may catalyze the oxidative reaction from rosmarinic acid to salvianolic acid B. These findings provide an invaluable genomic resource for understanding salvianolic acid B biosynthesis and its regulation, and will be useful for exploring the evolution of the Labiatae.
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http://dx.doi.org/10.1111/jipb.13085DOI Listing
February 2021

Targeted next-generation sequencing for cancer-associated gene mutation and copy number detection in 206 patients with non-small-cell lung cancer.

Bioengineered 2021 Dec;12(1):791-802

Translational Medicine Research Institute, Guangzhou Huayin Medical Laboratory Center Co., Ltd., Guangzhou, China.

The knowledge of genetic variation in Chinese patients with non-small-cell lung cancer (NSCLC) is still limited. We aimed to profile this genetic variation in 206 Chinese patients with NSCLC using next-generation sequencing. Tumor tissues or whole-blood samples were collected and subjected to whole-exome targeted next-generation sequencing, which included 565 tumor-associated genes, for somatic gene mutation screening and copy number variation (CNV) detection. Potential functions of most commonly mutated genes and genes with CNV were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Atotal of 18,749 mutations were identified using targeted next-generation sequencing, and 85.3% of them were missense mutations. Among the mutation, conversions between pyrimidine and purine were predominant, and C> T/G > A was the most common substitution type. High frequencies of mutations were noted in TP53 (47.6%), EGFR (41.7%), CREBBP (23.1%), KMT2C (16.9%), MUC2 (16.6%), DNMT3A (15.5%), LRP1B (15.5%), MUC4 (15.5%), CDC27 (15.2%), and KRAS (12.8%). EGFR and KRAS mutations were mutually exclusive. The tumor mutation load showed differences depending on gender and tumor type. CNV analysis showed that BCORL1 and ARAF have the highest copy number amplification, whereas KDM6A and RBM10 showed the highest copy number deletion. GO and KEGG analyses indicated that high-frequency mutations and CNV genes were concentrated in tumor-related PI3K-Akt, FoxO, and Ras signaling pathway. Cumulatively, we studied somatic gene mutations involved in NSCLC and predicted their clinical significance in Chinese population. These findings may provide clues for etiology and drug target of NSCLC.
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http://dx.doi.org/10.1080/21655979.2021.1890382DOI Listing
December 2021

Early Tracheostomy Change in Neonates: Feasibility and Benefits.

Otolaryngol Head Neck Surg 2021 Feb 23:194599821994744. Epub 2021 Feb 23.

Department of Otorhinolaryngology-Head and Neck Surgery, McGovern Medical School at the University of Texas Health Science Center, Houston, Texas, USA.

Objectives: To compare outcomes of early and late tracheostomy change in neonatal patients. Early tracheostomy change (ETC) occurred 3 to 4 days after surgery, and late tracheostomy change (LTC) occurred 5 to 7 days after surgery.

Study Design: Retrospective cohort.

Setting: Tertiary neonatal/pediatric intensive care unit.

Methods: A retrospective review of patients who underwent tracheostomy from 2015 to 2019 was performed for infants <1 year old. Data were recorded regarding age at tracheostomy, days until tracheostomy tube change, postoperative complications, and total number of days on sedative or paralytic drugs.

Results: Forty-six patients were included: 18 (39%) were male, with a mean age of 140 days (SD, 78). Of these, 28 (61%) received ETC. There were no accidental decannulation events in either group. Wound breakdown developed in 4 (14%) patients with ETC versus 5 (28%) with LTC ( = .3). Use of FlexTend tracheostomy tubes was associated with decreased odds of breakdown (odds ratio, 0.03; = .01). Postoperatively, 46 (100%) patients received sedation, and 12 (26%) received paralysis. Mean duration of paralysis was 0.5 days in ETC as opposed to 2.2 days in LTC ( = .02) on univariate analysis, but the significance was not maintained on multivariate regression ( = .07).

Conclusions: ETC appears to be feasible in children less than a year of age. There does not appear to be an increased risk of accidental decannulation events or false passage tracts. Further investigations are warranted to investigate safety and possible impact on wound breakdown.
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http://dx.doi.org/10.1177/0194599821994744DOI Listing
February 2021

Quantitative Trait Locus Mapping and Identification of Candidate Genes Controlling Flowering Time in L.

Front Plant Sci 2020 3;11:626205. Epub 2021 Feb 3.

State Key Laboratory of Crop Stress Biology for Arid Areas/College of Agronomy, Northwest A&F University, Yangling, China.

Flowering time plays a vital role in determining the life-cycle period, yield, and seed quality of rapeseed ( L.) in certain environments. Quantitative trait locus (QTL) mapping to identify the genetic architecture of genes controlling flowering time helps accelerate the early maturity breeding process. In this study, simple sequence repeats (SSR) and specific-locus amplified fragment sequencing (SLAF-seq) technologies were adopted to map the QTLs for flowering time in four environments. As a result, three target intervals, , , and were identified. Among this, was considered as a novel interval, and as stable regions. Based on the parental re-sequencing data, 7,022 single nucleotide polymorphisms (SNPs) and 2,195 insertion-deletions (InDels) between the two parents were identified in these three target regions. A total of 186 genes possessed genetic variations in these intervals, 14 of which were related to flowering time involved in photoperiod, circadian clock, vernalization, and gibberellin pathways. Six InDel markers linked to flowering time were developed in the three target intervals, indicating that the results were credible in this study. These results laid a good foundation for further genetic studies on flowering-time regulation in L.
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http://dx.doi.org/10.3389/fpls.2020.626205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886670PMC
February 2021

Natural variations in a pectin acetylesterase gene, MdPAE10, contribute to prolonged apple fruit shelf life.

Plant Genome 2021 03 18;14(1):e20084. Epub 2021 Feb 18.

College of Horticulture, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian District, Beijing, 100193, China.

Room-temperature shelf life is a key factor in fresh market apple (Malus domestica Borkh.) quality and commercial value. To investigate the genetic and molecular mechanism underlying apple shelf life, quantitative trait loci (QTL) were identified using bulked segregant analysis via sequencing (BSA-seq). Ethylene emission, flesh firmness, or crispness of apple fruit from 1,273 F plants of M. asiatica Nakai 'Zisai Pearl' × M. domestica 'Golden Delicious' were phenotyped prior to and during 6 wk of room-temperature storage. Segregation of ethylene emission and the flesh firmness or crispness traits was detected in the population. Thirteen QTL, including three major ones, were identified on chromosome 03, 08, and 16. A candidate gene encoding pectin acetylesterase, MdPAE10, from the QTL Z16.1 negatively affected fruit shelf life. A 379-bp deletion in the coding sequence of MdPAE10 disrupted its function. A single nucleotide polymorphism (SNP) in the MdPAE10 promoter region reduced its transcription activity. These findings provided insight into the genetic control of fruit shelf life and can be potentially used in apple marker-assisted selection.
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http://dx.doi.org/10.1002/tpg2.20084DOI Listing
March 2021

Optimized Biocatalytic Synthesis of 2-Selenopyrimidine Nucleosides by Transglycosylation.

Chembiochem 2021 Feb 17. Epub 2021 Feb 17.

Technische Universität Berlin Faculty III Process Sciences, Institute of Biotechnology Chair of Bioprocess Engineering, Ackerstraße 76, 13355, Berlin, Germany.

Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40-48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6-40 % isolated yield, which compares favorably to established chemical routes.
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http://dx.doi.org/10.1002/cbic.202100067DOI Listing
February 2021

Development of a Metastasis-Related Immune Prognostic Model of Metastatic Colorectal Cancer and Its Usefulness to Immunotherapy.

Front Cell Dev Biol 2020 28;8:577125. Epub 2021 Jan 28.

Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Post-surgical recurrence of the metastatic colorectal cancer (mCRC) remains a challenge, even with adjuvant therapy. Moreover, patients show variable outcomes. Here, we set to identify gene models based on the perspectives of intrinsic cell activities and extrinsic immune microenvironment to predict the recurrence of mCRC and guide the adjuvant therapy. An RNA-based gene expression analysis of CRC samples (total = 998, including mCRCs = 344, non-mCRCs = 654) was performed. A metastasis-evaluation model (MEM) for mCRCs was developed using the Cox survival model based on the prognostic differentially expressed genes between mCRCs and non-mCRCs. This model separated the mCRC samples into high- and low-recurrence risk clusters that were tested using machine learning to predict recurrence. Further, an immune prognostic model (IPM) was built using the COX survival model with the prognostic differentially expressed immune-related genes between the two MEM risk clusters. The ability of MEM and IPM to predict prognosis was analyzed and validated. Moreover, the IPM was utilized to evaluate its relationship with the immune microenvironment and response to immuno-/chemotherapy. Finally, the dysregulation cause of IPM three genes was analyzed in bioinformatics. A high post-operative recurrence risk was observed owing to the downregulation of the immune response, which was influenced by MEM genes () and their related IPM genes (). The MEM and IPM were developed and validated through mCRC samples to differentiate between low- and high-recurrence risk in a real-world cohort. The functional enrichment analysis suggested pathways related to immune response and immune system diseases as the major functional pathways related to the IPM genes. The IPM high-risk group (IPM-high) showed higher fractions of regulatory T cells (Tregs) and smaller fractions of resting memory CD4+ T cells than the IPM-low group. Moreover, the stroma and immune cells in the IPM-high samples were scant. Further, the IPM-high group showed downregulation of MHC class II molecules. Additionally, the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and GDSC analysis suggested the IPM-low as a promising responder to anti-CTLA-4 therapy and the common FDA-targeted drugs, while the IPM-high was non-responsive to these treatments. However, treatment using anti-CDKN2A agents, along with the activation of major histocompatibility complex (MHC) class-II response might sensitize this refractory mCRC subgroup. The dysfunction of might be the reason for the dysregulation of IPM genes. The IPM could identify subgroups of mCRC with a distinct risk of recurrence and stratify the patients sensitive to immuno-/chemotherapy. Further, for the first time, our study highlights the importance of MHC class-II molecules in the treatment of mCRCs using immunotherapy.
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http://dx.doi.org/10.3389/fcell.2020.577125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876250PMC
January 2021

A Nomogram Model Involving Immunohistochemical Markers for Predicting the Recurrence of Stage I-II Endometrial Cancer.

Front Oncol 2020 22;10:586081. Epub 2021 Jan 22.

Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: The purpose of this study was to establish a nomogram combining classical parameters and immunohistochemical markers to predict the recurrence of patients with stage I-II endometrial cancer (EC).

Methods: 419 patients with stage I-II endometrial cancer who received primary surgical treatment at the First Affiliated Hospital of Chongqing Medical University were involved in this study as a training cohort. Univariate and multivariate Cox regression analysis of screening prognostic factors were performed in the training cohort to develop a nomogram model, which was further validated in 248 patients (validation cohort) from the Second Affiliated Hospital of Chongqing Medical University. The calibration curve was used for internal and external verification of the model, and the C-index was used for comparison among different models.

Results: There were 51 recurrent cases in the training cohort while 31 cases in the validation cohort. Univariate analysis showed that age, histological type, histological grade, myometrial invasion, cervical stromal invasion, postoperative adjuvant treatment, and four immunohistochemical makers (Ki67, estrogen receptor, progesterone receptor, P53) were the related factors for recurrence of EC. Multivariate analysis demonstrated that histological type (P = 0.029), myometrial invasion (P = 0.003), cervical stromal invasion (P = 0.001), Ki67 (P < 0.001), ER (P = 0.009) and P53 expression (P = 0.041) were statistically correlated with recurrence of EC. Recurrence-free survival was better predicted by the proposed nomogram with a C-index of 0.832 (95% CI, 0.752-0.912) in the training cohort, and the validation set confirmed the finding with a C-index of 0.861 (95% CI, 0.755-0.967).

Conclusion: The nomogram model combining classical parameters and immunohistochemical markers can better predict the recurrence in patients with FIGO stage I-II EC.
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http://dx.doi.org/10.3389/fonc.2020.586081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874072PMC
January 2021

Treatment of periodontal intrabony defects using bovine porous bone mineral and guided tissue regeneration with/without platelet-rich fibrin: a randomized controlled clinical trial.

J Periodontol 2021 Feb 10. Epub 2021 Feb 10.

Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, China.

Background: To investigate the regenerative effect of adjunctive use of guided tissue regeneration (GTR), bovine porous bone mineral (BPBM), and platelet-rich fibrin (PRF) in intrabony defects.

Methods: Fourteen participants were enrolled, and for each patient their left and right two sides were randomized to the test group or control group. Only the worst intrabony defect on each side was analyzed. The test group received GTR, BPBM, and PRF, whereas the control group received only GTR and BPBM. The PRF used in the trial was fluid PRF, which combined with the BPBM to form a BPBM-PRF complex. The patients were followed up by clinical and radiographic evaluation for 24 months after surgery.

Results: Probing depth (PD) in the test group was significantly less than that in the control group at 12 and 24 months after surgery, and the mean difference was ≈ 0.5 to 0.7 mm. Clinical attachment level (CAL) gain in the test group was ≈ 0.9 mm higher than that in the control group at 6 months after surgery, and the difference reached 1.0 to 1.1 mm 12 and 24 months after surgery. None of the other clinical or radiographic parameters differed significantly between the two groups at any time-point after the surgery.

Conclusion: Compared with GTR and BPBM, the combination of GTR and BPBM-PRF complex is more effective clinically, and results in better clinical outcomes.
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http://dx.doi.org/10.1002/JPER.20-0860DOI Listing
February 2021

Sensitive tracking of circulating viral RNA through all stages of SARS-CoV-2 infection.

J Clin Invest 2021 04;131(7)

Center for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, Louisiana, USA.

BACKGROUNDCirculating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA may represent a more reliable indicator of infection than nasal RNA, but quantitative reverse transcription PCR (RT-qPCR) lacks diagnostic sensitivity for blood samples.METHODSA CRISPR-augmented RT-PCR assay that sensitively detects SARS-CoV-2 RNA was employed to analyze viral RNA kinetics in longitudinal plasma samples from nonhuman primates (NHPs) after virus exposure; to evaluate the utility of blood SARS-CoV-2 RNA detection for coronavirus disease 2019 (COVID-19) diagnosis in adults cases confirmed by nasal/nasopharyngeal swab RT-PCR results; and to identify suspected COVID-19 cases in pediatric and at-risk adult populations with negative nasal swab RT-qPCR results. All blood samples were analyzed by RT-qPCR to allow direct comparisons.RESULTSCRISPR-augmented RT-PCR consistently detected SARS-CoV-2 RNA in the plasma of experimentally infected NHPs from 1 to 28 days after infection, and these increases preceded and correlated with rectal swab viral RNA increases. In a patient cohort (n = 159), this blood-based assay demonstrated 91.2% diagnostic sensitivity and 99.2% diagnostic specificity versus a comparator RT-qPCR nasal/nasopharyngeal test, whereas RT-qPCR exhibited 44.1% diagnostic sensitivity and 100% specificity for the same blood samples. This CRISPR-augmented RT-PCR assay also accurately identified patients with COVID-19 using one or more negative nasal swab RT-qPCR results.CONCLUSIONResults of this study indicate that sensitive detection of SARS-CoV-2 RNA in blood by CRISPR-augmented RT-PCR permits accurate COVID-19 diagnosis, and can detect COVID-19 cases with transient or negative nasal swab RT-qPCR results, suggesting that this approach could improve COVID-19 diagnosis and the evaluation of SARS-CoV-2 infection clearance, and predict the severity of infection.TRIAL REGISTRATIONClinicalTrials.gov. NCT04358211.FUNDINGDepartment of Defense, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, and the National Center for Research Resources.
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http://dx.doi.org/10.1172/JCI146031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011898PMC
April 2021

What is the optimal number of neoadjuvant chemotherapy cycles for resectable colorectal liver oligometastases?

Ann Transl Med 2021 Jan;9(1)

Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: The optimal number of neoadjuvant chemotherapy (NAC) cycles for resectable colorectal liver oligometastases (CLOM) remains unclear. The aim of this study was to investigate the optimal number of NAC cycles.

Methods: One hundred twenty-nine consecutive patients were included in this study. X-tile analysis was implemented to investigate the optimal cut-off point for NAC cycles. Propensity score matching was performed to reduce selection bias. Kaplan-Meier curves and Cox risk regression models were used to analyse progression-free survival (PFS) and overall survival (OS).

Results: The optimal cut-off point for NAC cycles was 5. There were no significant differences in R0 resection, pathological response or postoperative complications between the groups with a low number of NAC cycles group (≤5 cycles, n=80) and high number of NAC cycles (>5 cycles, n=49). Patients with a high number of NAC cycles were more likely to have NAC toxicity than those with a low number of cycles (87.8% 65.0%, P=0.004). Multivariate analysis revealed that >5 NAC cycles was an independent predictor of reduced PFS (HR =1.808, 95% CI: 1.205-2.712, P=0.004) and reduced OS (HR =1.723, 95% CI: 1.041-2.851, P=0.034). In the oxaliplatin-based regimen group, patients with a low number of NAC cycles had a better PFS (P<0.001, mPFS: 14.7 5.4 months) and better OS (P=0.018, mOS: 57.7 months 41.0 months) than those with a high number of cycles. After 1:1 propensity matching (34 cases 34 cases), multivariate analysis revealed that >5 NAC cycles was an independent predictor of reduced PFS (HR =2.265, 95% CI: 1.281-4.007, P=0.005) and reduced OS (HR =2.813, 95% CI: 1.359-5.822, P=0.005). In the oxaliplatin-based regimen group, patients with a low number of NAC cycles had better PFS (P<0.001, mPFS: 17.5 5.6 months) and better OS (P=0.008, mOS: 59.0 31.8 months) than those with a high number of cycles.

Conclusions: Fewer than 5 NAC cycles was optimal for biologically resectable CLOM patients. Giving more than 5 NAC cycles was unnecessary because a higher number of NAC cycles has more unfavourable survival and higher NAC toxicities, while leading to similar R0 resection rates and pathological responses.
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http://dx.doi.org/10.21037/atm-20-4289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859783PMC
January 2021

Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20 B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis.

Sci Rep 2021 Feb 5;11(1):3255. Epub 2021 Feb 5.

Institute of Infectious Disease, Southwest Hospital, Third Military Medical University, Chongqing, China.

Rituximab combined with chemotherapy is the first-line induction therapy of CD20 positive B-cell non-Hodgkin lymphomas (CD20 B-NHL). Recently new anti-CD20 monoclonal antibodies (mAbs) have been developed, but their efficacy and safety compared with rituximab are still controversial. We searched MEDLINE, Embase, and Cochrane Library for eligible randomized controlled trials (RCTs) that compared new anti-CD20 mAbs with rituximab in induction therapy of B-NHL. The primary outcomes are progression-free survival (PFS) and overall survival (OS), additional outcomes include event-free survival (EFS), disease-free survival (DFS), overall response rate (ORR), complete response rate (CRR) and incidences of adverse events (AEs). Time-to-event data were pooled as hazard ratios (HRs) using the generic inverse-variance method and dichotomous outcomes were pooled as odds ratios (ORs) using the Mantel-Haenszel method with their respective 95% confidence interval (CI). Eleven RCTs comprising 5261 patients with CD20 B-NHL were included. Compared with rituximab, obinutuzumab significantly prolonged PFS (HR 0.84, 95% CI 0.73-0.96, P = 0.01), had no improvement on OS, ORR, and CRR, but increased the incidences of serious AEs (OR 1.29, 95% CI 1.13-1.48, P < 0.001). Ofatumumab was inferior to rituximab in consideration of ORR (OR 0.73, 95% CI 0.55-0.96, P = 0.02), and had no significant differences with rituximab in regard to PFS, OS and CRR. I-tositumomab yielded similar PFS, OS, ORR and CRR with rituximab. Y-ibritumomab tiuxetan increased ORR (OR 3.07, 95% CI 1.47-6.43, P = 0.003), but did not improve PFS, DFS, OS and CRR compared with rituximab. In conclusion, compared with rituximab in induction therapy of CD20 B-NHL, obinutuzumab significantly improves PFS but with higher incidence of AEs, ofatumumab decreases ORR, Y-ibritumomab tiuxetan increases ORR.
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http://dx.doi.org/10.1038/s41598-021-82841-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864901PMC
February 2021

Rice MutLγ, the MLH1-MLH3 heterodimer, participates in the formation of type I crossovers and regulation of embryo sac fertility.

Plant Biotechnol J 2021 Feb 5. Epub 2021 Feb 5.

State Key Laboratory of Hybrid Rice, Hunan Hybrid Rice Research Center, Changsha, China.

The development of embryo sacs is crucial for seed production in plants, but the genetic basis regulating the meiotic crossover formation in the macrospore and microspore mother cells remains largely unclear. Here, we report the characterization of a spontaneous rice female sterile variation 1 mutant (fsv1) that showed severe embryo sacs abortion with low seed-setting rate. Through map-based cloning and functional analyses, we isolated the causal gene of fsv1, OsMLH3 encoding a MutL-homolog 3 protein, an ortholog of HvMLH3 in barley and AtMLH3 in Arabidopsis. OsMLH3 and OsMLH1 (MutL-homolog 1) interact to form a heterodimer (MutLγ) to promote crossover formation in the macrospore and microspore mother cells and development of functional megaspore during meiosis, defective OsMLH3 or OsMLH1 in fsv1 and CRISPR/Cas9-based knockout lines results in reduced type I crossover and bivalent frequency. The fsv1 and OsMLH3-knockout lines are valuable germplasms for development of female sterile restorer lines for mechanized seed production of hybrid rice.
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http://dx.doi.org/10.1111/pbi.13563DOI Listing
February 2021

Significance of Oncotype DX 21-Gene Test and Expression of Long Non-Coding RNA MALAT1 in Early and Estrogen Receptor-Positive Breast Cancer Patients.

Cancer Manag Res 2021 22;13:587-593. Epub 2021 Jan 22.

Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.

Objective: To investigate the association between the recurrence score (RS) obtained by Oncotype test and long non-coding RNA (lncRNA) expression in early and estrogen receptor-positive (ER) breast cancer.

Materials And Methods: The Oncotype test and expression detection were performed in tumor samples from 76 ER and early breast cancer patients with the Surplex liquid chip. The RS value was calculated based on the expression of total 21 genes. The level of was measured in both tumor tissue and para-tumor tissue, and relatively quantified with an internal control gene. Mann-Whitney -test or Kruskal-Wallis test were used to analyze the association between level and different clinical pathological characteristics, including age, tumor stage, disease grade, lymph node status, Ki-67 expression, and progesterone receptor (PR) status. The association between the RS and different characteristics was analyzed by Wilcoxon rank-sum test. Correlation between two parameters was analyzed by Spearman's rank correlation analysis.

Results: The expression of was more abundant in tumor tissue (2.992 ± 2.256) than that in adjacent normal tissue (1.641±1.438, =-2.594, 0.009), and it was not correlated with any clinical pathological characteristics. According to the old criteria for RS stratification, 52.7% of patients were in low risk (RS<18), 36.8% of patients were in medium risk (18≤RS≤30), and 10.5% of patients were in high risk (RS>30). While under the new criteria, 18.4% were in low risk group (RS<11), 63.2% were in a medium risk group (11≤RS≤26), and 18.4% were in a high risk group (RS>26). The Oncotype results only correlated with Ki-67 expression under both new and old criteria, and it was not related with other cancer characteristics. The expression of lncRNA was significantly correlated with the Oncotype results under the old criteria.

Conclusion: is a novel breast cancer biomarker independent of tumor stage, disease grade and lymph node status. level is associated with the Oncotype RS value. Therefore, combination of and the Oncotype test may be used to predict prognosis in ER and early stage breast cancer.
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http://dx.doi.org/10.2147/CMAR.S276795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837574PMC
January 2021