Publications by authors named "Li Xie"

819 Publications

Exogenous insulin-like growth factor 1 attenuates sevoflurane anesthesia-induced cognitive dysfunction in aged rats.

J Neurophysiol 2021 May 5. Epub 2021 May 5.

Department of Anesthesiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Chinagrid.59053.3a.

Sevoflurane anesthesia is correlated with the generation of postoperative cognitive dysfunction. Insulin-like growth factor 1 (IGF-1) has important function in the nervous system development. Intravenously injected IGF-1 is reported to successfully pass the blood-brain barrier and perform neuroprotection effect in the brain. Memory and learning abilities were analyzed through Morris water maze task. Relative levels of protein were examined through Western blot and enzyme-linked immunosorbent assay (ELISA). Relative mRNA levels were shown through quantitative real time-polymerase chain reaction (qRT-PCR). IGF-1 expression in the plasma and hippocampus was downregulated in sevoflurane anesthesia-induced rats and rescued by intravenous IGF-1 injection. In aged rats, intravenous injection of IGF-1 alleviated sevoflurane-caused cognitive injuries and elevated TNF-⍺, IL-1β and IL-6 levels in the plasma and hippocampus and rescued sevoflurane-depressed Akt phosphorylation. In conclusion, the administration of IGF-1 through intravenous injection alleviates sevoflurane anesthesia-mediated neuroinflammation and cognitive impairment in rats. The effects of IGF-1 in this process may depend on its function in regulating the PI3K/Akt signaling pathway.
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http://dx.doi.org/10.1152/jn.00124.2021DOI Listing
May 2021

Transcriptome Based Estrogen Related Genes Biomarkers for Diagnosis and Prognosis in Non-small Cell Lung Cancer.

Front Genet 2021 14;12:666396. Epub 2021 Apr 14.

Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Lung cancer is the tumor with the highest morbidity and mortality, and has become a global public health problem. The incidence of lung cancer in men has declined in some countries and regions, while the incidence of lung cancer in women has been slowly increasing. Therefore, the aim is to explore whether estrogen-related genes are associated with the incidence and prognosis of lung cancer.

Methods: We obtained all estrogen receptor genes and estrogen signaling pathway genes in The Cancer Genome Atlas (TCGA), and then compared the expression of each gene in tumor tissues and adjacent normal tissues for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) separately. Survival analysis was performed of the differentially expressed genes in LUAD and LUSC patients separately. The diagnostic and prognostic values of the candidate genes were validated in the Gene Expression Omnibus (GEO) datasets.

Results: We found 5 estrogen receptor genes and 66 estrogen pathway genes in TCGA. A total of 50 genes were differently expressed between tumor tissues and adjacent normal tissues and 6 of the 50 genes were related to the prognosis of LUAD in TCGA. 56 genes were differently expressed between tumor tissues and adjacent normal tissues and none of the 56 genes was related to the prognosis of LUSC in TCGA. GEO datasets validated that the 6 genes () had different expression between tumor tissues and adjacent normal tissues in LUAD, and 3 genes () were related to the prognosis of LUAD.

Conclusions: The expressions of and are related to the pathogenesis and prognosis of LUAD. and may serve as biomarkers in LUAD screening and prognosis prediction in clinical settings.
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http://dx.doi.org/10.3389/fgene.2021.666396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081391PMC
April 2021

Laboratory indicators predict axillary nodal pathologic complete response after neoadjuvant therapy in breast cancer.

Future Oncol 2021 Apr 21. Epub 2021 Apr 21.

Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250000, PR China.

 The purpose was to integrate clinicopathological and laboratory indicators to predict axillary nodal pathologic complete response (apCR) after neoadjuvant therapy (NAT). The pretreatment clinicopathological and laboratory indicators of 416 clinical nodal-positive breast cancer patients who underwent surgery after NAT were analyzed from April 2015 to 2020. Predictive factors of apCR were examined by logistic analysis. A nomogram was built according to logistic analysis. Among the 416 patients, 37.3% achieved apCR. Multivariate analysis showed that age, pathological grading, molecular subtype and neutrophil-to-lymphocyte ratio were independent predictors of apCR. A nomogram was established based on these four factors. The area under the curve (AUC) was 0.758 in the training set. The validation set showed good discrimination, with AUC of 0.732. In subtype analysis, apCR was 23.8, 47.1 and 50.8% in hormone receptor-positive/HER2-, HER2+ and triple-negative subgroups, respectively. According to the results of the multivariate analysis, pathological grade and fibrinogen level were independent predictors of apCR after NAT in HER2+ patients. Except for traditional clinicopathological factors, laboratory indicators could also be identified as predictive factors of apCR after NAT. The nomogram integrating pretreatment indicators demonstrated its distinguishing capability, with a high AUC, and could help to guide individualized treatment options.
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http://dx.doi.org/10.2217/fon-2020-1231DOI Listing
April 2021

Assessment of perinodular stiffness in differentiating malignant from benign thyroid nodules.

Endocr Connect 2021 May 10;10(5):492-501. Epub 2021 May 10.

Division of Life Sciences and Medicine, Department of Ultrasound, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.

Objective: We evaluated the diagnostic accuracy of perinodular stiffness, four risk stratification systems (RSSs) (KWAK-TIRADS, ACR-TIRADS, EU-TIRADS, and C-TIRADS), and the combination of perinodular stiffness and the four RSSs in differentiating malignant from benign thyroid nodules (TNs).

Methods: A total of 788 TNs in 726 patients were examined with conventional ultrasound (US) examination and sound touch elastography (STE). All TNs were classified by each of the four RSSs. The stiffness inside (E) the TNs was measured by STE. The stiffness of the 2.0-mm perinodular region (Eshell) was measured with the Shell measurement function of STE. The diagnostic performances of four RSSs, the E values, and the Eshell values were evaluated. All TNs were further divided into subgroups based on size (≤ 10 mm group and > 10 mm group).

Results: Ninety-six TNs were classified as benign and 692 as malignant. Among the single-method approaches, ACR-TIRADS showed the highest AUC (0.77) for differentiating malignant from benign TNs for all TNs included. Eshell showed the highest AUC (0.75) in differentiating malignant from benign TNs for TNs with sizes ≤ 10 mm, and there were no significant differences in AUC among all single methods for diagnosis of TNs with sizes > 10 mm (P > 0.05). The combination of C-TIRADS and Eshell/E yielded the highest AUC for all TNs (0.83) and for TNs with size ≤ 10 mm (0.85) compared with other combinations.

Conclusions: Eshell/E combined with conventional US improves the diagnostic accuracy in TNs and may reduce unnecessary fine-needle aspiration.
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http://dx.doi.org/10.1530/EC-21-0034DOI Listing
May 2021

Prolonged use of bedaquiline in two patients with pulmonary extensively drug-resistant tuberculosis: Two case reports.

World J Clin Cases 2021 Apr;9(10):2326-2333

Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.

Background: Bedaquiline is among the prioritized drugs recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis (XDR-TB). Many patients have not achieved better clinical improvement after bedaquiline is stopped at 24 wk. However, there is no recommendation or guideline on bedaquiline administration beyond 24 wk, which is an important consideration when balancing the benefit of prognosis for XDR-TB against the uncertain safety concerning the newer antibiotics.

Case Summary: This paper reported 2 patients with XDR-TB (a female of 58 years of age and a female of 18 years of age) who received bedaquiline for 36 wk, as local experience to be shared. The 2 cases had negative cultures after 24 wk of treatment, but lung imaging was still positive. After discussion among experts, the consensus was made to bedaquiline prolongation by another 12 wk. The 36-wk prolonged use of bedaquiline in both cases achieved a favorable response without increasing the risk of cardiac events or new safety signals.

Conclusion: Longer regimen, including 36-wk bedaquiline treatment, might be an option for patients with XDR-TB. More studies are needed to explore the effectiveness and safety of prolonged use of bedaquiline for 36 wk standard 24 wk in the treatment of multidrug-resistant/XDR-TB or to investigate further the biomarkers and criteria indicative for extension of bedaquline to facilitate clinical use of this novel drug.
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http://dx.doi.org/10.12998/wjcc.v9.i10.2326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026830PMC
April 2021

Biocompatible Nanoparticles as a Platform for Enhancing Antitumor Efficacy of Cisplatin-Tetradrine Combination.

Nanoscale Res Lett 2021 Apr 14;16(1):61. Epub 2021 Apr 14.

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Combination therapy has been a standard strategy in the clinical tumor treatment. We have demonstrated that combination of Tetradrine (Tet) and Cisplatin (CDDP) presented a marked synergistic anticancer activity, but inevitable side effects limit their therapeutic concentration. Considering the different physicochemical and pharmacokinetic properties of the two drugs, we loaded them into a nanovehicle together by the improved double emulsion method. The nanoparticles (NPs) were prepared from the mixture of poly(ethyleneglycol)-polycaprolactone (PEG-PCL) and polycarprolactone (HO-PCL), so CDDP and Tet can be located into the NPs simultaneously, resulting in low interfering effect and high stability. Images from fluorescence microscope revealed the cellular uptake of both hydrophilic and hydrophobic agents delivered by the NPs. In vitro studies on different tumor cell lines and tumor tissue revealed increased tumor inhibition and apoptosis rates. As to the in vivo studies, superior antitumor efficacy and reduced side effects were observed in the NPs group. Furthermore, FDG-PET/CT imaging demonstrated that NPs reduced metabolic activities of tumors more prominently. Our results suggest that PEG-PCL block copolymeric NPs could be a promising carrier for combined chemotherapy with solid efficacy and minor side effects.
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http://dx.doi.org/10.1186/s11671-021-03511-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046896PMC
April 2021

An internet-based multidisciplinary online medical consultation system to help cope with pediatric medical needs during the COVID-19 outbreak: a cross-sectional study.

Transl Pediatr 2021 Mar;10(3):560-568

Department of Pulmonology, Children's Hospital of Fudan University, Shanghai, China.

Background: Telemedicine is becoming an emerging innovative supplement to the traditional medical system in China. In the present study, we described the rapid implementation of the telemedicine in pediatrics during the coronavirus disease 2019 (COVID-19) outbreak and explored its value in response to the demand for pediatric medical services during the epidemic.

Methods: An Internet-based platform for multidisciplinary online medical consultation was established on February 8, 2020, by a national children's medical center in China. The medical data of the traditional hospital visits and novel online visits from the first two months (February 8 to March 31) after the establishment of the platform were collected and analyzed. The demographic features, changes in the disease spectrum and characteristics of online medical services were described.

Results: The total number of visits was significantly lower (by 75.3%) than that of in the same period in the previous year. The disease spectrum was different with a significant decrease of >95% in the number of patients with infectious or contagious diseases. The online visits accounted for 14.7% of all visits. Online patients came from all over the country, covering 91% of the administrative regions of China, and the largest proportion of inquiries were for infants (33.7%) (P<0.01). The response rate of experts to requests for online consultations was 100%. During the study period, 266 experts from 25 pediatric specialties completed 12,318 effective consultations, proving different degrees of online supplementation for various specialties (4.3-168.4%). Online consultations mainly addressed two types of problems: (I) accessibility of the traditional hospital visits and (II) consultations regarding an illness. Data from pediatric nephrology showed that 96% of the patients with stable chronic kidney disease successfully received follow-up medication adjustment guidance through the online platform.

Conclusions: The traditional hospital medical services have been affected by the COVID-19 outbreak. The multidisciplinary online medical consultation system is a strategy to actively respond to the medical needs of children during unique periods.
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http://dx.doi.org/10.21037/tp-20-348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039788PMC
March 2021

A novel protein encoded by circMAPK1 inhibits progression of gastric cancer by suppressing activation of MAPK signaling.

Mol Cancer 2021 04 9;20(1):66. Epub 2021 Apr 9.

Division of Gastric Surgery, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, People's Republic of China.

Background: A novel type of noncoding RNA, circRNA has been reported to participate in the occurrence and development of diseases through many mechanisms. The MAPK pathway is a common signal transduction pathway involved in cell proliferation, inflammation and apoptosis and plays a particularly important role in cancers. However, the role of circRNAs related to the MAPK pathway in gastric cancer has not been explored.

Methods: A bioinformatics analysis was performed to profile and identify the circRNAs involved in the MAPK pathway in gastric cancer. The tumor-suppressive role of circMAPK1 was confirmed both in vitro and in vivo. Mass spectrometry, Western blot and immunofluorescence staining assays were used to validate the existence and expression of MAPK1-109aa. The molecular mechanism of circMAPK1 was investigated by mass spectrometry and immunoprecipitation analyses.

Results: In this study, we identified that circMAPK1 (hsa_circ_0004872) was downregulated in gastric cancer tissues compared with adjacent normal tissues. Importantly, lower circMAPK1 expression predicted poor survival in GC patients. CircMAPK1 inhibited the proliferation and invasion of gastric cancer cells in vitro and in vivo. Next, we found that circMAPK1 encoded a novel protein with 109 amino acids in length. Through a series of functional experiments, we confirmed that circMAPK1 exerted a tumor-suppressing effect via the encoded protein MAPK1-109aa. Mechanistically, the tumor suppressor MAPK1-109aa inhibited the phosphorylation of MAPK1 by competitively binding to MEK1, thereby suppressing the activation of MAPK1 and its downstream factors in MAPK pathway.

Conclusions: Our study revealed that circMAPK1 inhibits the malignant biological behavior of gastric cancer cells through its encoded protein MAPK1-109aa. More importantly, circMAPK1 is a favorable predictor for gastric cancer patients and may provide a new therapeutic target in the treatment of gastric cancer.
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http://dx.doi.org/10.1186/s12943-021-01358-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034133PMC
April 2021

Improved quantification of immune-gold labeling and its use to compare the distribution of cellular factors among sub-chloroplast compartments.

Micron 2021 Mar 18;145:103060. Epub 2021 Mar 18.

Institute of Virology and Biotechnology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China. Electronic address:

Quantification of immuno-gold labeling can provide valuable information on the quantity and localization of a target within a region of interest (ROI). Background subtraction usually requires preparation of material with a deliberately reduced amount of target component often by gene knockout/knockdown. This paper reports a modified method without the need for gene knockout/knockdown, by using a region outside the ROI as a background and non-immune serum to verify the reliability of the data. An optimized parameter for use in image processing was also developed to improve semi-automatic segmentation of gold particles, by using the standard deviation of pixel intensity together with default parameters (size and intensity) to improve specificity. The modified methods were used to quantify the gold labeling of various components within chloroplasts and their 3 sub-organelle compartments (thylakoid, stroma and starch). Rubisco, actin, myosin, β-tubulin, Endoplasmic reticulum-retention signal HDEL, Sterol methyltransferase 1, and double stranded RNA were all effectively and consistently quantified at the level of the different sub-chloroplast compartments. The approach should be applicable more widely for high resolution labelling of samples in which a background requiring gene knockout/knockdown is not a realistic option.
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http://dx.doi.org/10.1016/j.micron.2021.103060DOI Listing
March 2021

Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials.

J Immunother Cancer 2021 Apr;9(4)

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China

Background: Progression-free survival (PFS) exhibits suboptimal performance as the surrogate endpoint for overall survival (OS) in trials studying immune checkpoint inhibitors (ICIs). Here we propose a novel surrogate endpoint, modified PFS (mPFS), which omits the events of disease progression (but not deaths) within 3 months after randomization.

Methods: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for randomized trials studying ICIs in advanced solid tumors with available PFS and OS data up to May 2020. Individual patient-level data (IPD) for PFS and OS were reconstructed for eligible trials. A simulation-based algorithm was used to match the reconstructed, disconnected PFS and OS IPD, and 1000 independent simulated datasets of matched PFS-OS IPD were generated for each trial. mPFS durations and statuses were then measured for each of the matched PFS-OS IPD. Trial-level correlation between Cox HRs for PFS or mPFS and HRs for OS was assessed using Pearson correlation coefficient (r) weighted by trial size; patient-level correlation between PFS or mPFS and OS was assessed using Spearman's rank correlation coefficient (r). Findings were further validated using the original IPD from two randomized ICI trials.

Results: Fifty-seven ICI trials totaling 29,429 participants were included. PFS HR showed moderate correlation with OS HR (r=0.60), and PFS was moderately correlated with OS at the patient level (median r=0.66; range, 0.65-0.68 among the 1000 simulations). In contrast, mPFS HR achieved stronger correlation with OS HR (median r=0.81; range, 0.77-0.84), and mPFS was more strongly correlated with OS at the patient level (median r=0.79; range, 0.78-0.80). The superiority of mPFS over PFS remained consistent in subgroup analyses by cancer type, therapeutic regimen, and treatment setting. In both trials with the original IPD where experimental treatment significantly improved OS, mPFS successfully captured such clinical benefits whereas PFS did not.

Conclusions: mPFS outperformed PFS as the surrogate endpoint for OS in ICI trials. mPFS is worthy of further investigation as a secondary endpoint in future ICI trials.
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http://dx.doi.org/10.1136/jitc-2020-002114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021890PMC
April 2021

TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 as novel biomarkers for lung cancer diagnosis and progression prediction.

J Cancer Res Clin Oncol 2021 Jun 29;147(6):1609-1622. Epub 2021 Jan 29.

Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Ji-Yan Road, Jinan, 250117, Shandong Province, People's Republic of China.

Purpose: Platelets contain a rich repertoire of RNA species, such as mRNAs and long non-coding RNAs. During the development of tumors, platelets are "educated" by cancer cells, altering their transcriptome and molecular content, thereby, tumor educated platelet (TEP) lncRNA profile has the potential to diagnose lung cancer. The current study was aimed to examine whether TEPs might be a potential biomarker for lung cancer.

Methods: Platelet precipitation was obtained by low-speed centrifugation. TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 were selected by lncRNA microarray and validated by qPCR in a large cohort of lung cancer patients and healthy donors. Besides, we analyzed the association of their expression levels with clinicopathological features.

Results: TEP linc-GTF2H2-1 and RP3-466P17.2 were significantly downregulated, while lnc-ST8SIA4-12 was significantly upregulated in patients with lung cancer or with early-stage lung cancer as compared to healthy donors, possessing AUCs of 0.781, 0.788, 0.725 for lung cancer and 0.704, 0.771, 0.768 for early-stage lung cancer, respectively. Notably, their combination demonstrated the markedly elevated AUCs of 0.921 for lung cancer and 0.895 for early-stage lung cancer. Besides, the combination of TEP linc-GTF2H2-1 was capable to facilitate diagnostic efficiencies of CEA, Cyfra21-1, or NSE to distinguish advanced-stage lung cancer patients from early ones, with an AUC of 0.899 based on the integration of these four factors.

Conclusion: Our data suggested that lncRNAs sequestered in TEPs enabled blood-based lung cancer diagnosis and progression prediction.
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http://dx.doi.org/10.1007/s00432-020-03502-5DOI Listing
June 2021

Circulating Serum Exosomal Long Non-Coding RNAs FOXD2-AS1, NRIR, and XLOC_009459 as Diagnostic Biomarkers for Colorectal Cancer.

Front Oncol 2021 12;11:618967. Epub 2021 Mar 12.

Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Background: Exosomes derived from cancer cells encapsulate various kinds of tumor-specific molecules and thus can interact with adjacent or distant cells to mediate information exchange. Long non-coding RNAs (lncRNAs) in exosomes have the potential as diagnostic and prognostic biomarkers in different types of cancers. The current study was aimed to identify circulating exosomal lncRNAs for the diagnosis of colorectal cancer (CRC).

Methods: Exosomes were isolated from the serum by ultracentrifugation and verified by transmission electron microscope (TEM), qNano, and immunoblotting. Exosomal lncRNAs FOXD2-AS1, NRIR, and XLOC_009459 were selected by lncRNA microarray and validated by qPCR in 203 CRC patients and 201 healthy donors. The receiver operating characteristic curve (ROC) was used to assess the diagnostic efficiency of serum exosomal lncRNAs.

Results: Exosomal FOXD2-AS1, NRIR, and XLOC_009459 (TCONS_00020073) levels were significantly upregulated in 203 CRC patients and 80 early-stage CRC patients compared to 201 healthy donors, possessing the area under the curve (AUC) of 0.728, 0.660, and 0.682 for CRC, as well as 0.743, 0.660, and 0.689 for early-stage CRC, respectively. Notably, their combination demonstrated the markedly elevated AUC of 0.736 for CRC and 0.758 for early-stage CRC, indicating their potential as diagnostic biomarkers for CRC.

Conclusions: Our data suggested that exosomal lncRNAs FOXD2-AS1, NRIR, and XLOC_009459 act as the promising biomarkers for the diagnostics of CRC and early-stage CRC.
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http://dx.doi.org/10.3389/fonc.2021.618967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996089PMC
March 2021

Values of liquid biopsy in early detection of cancer: results from meta-analysis.

Expert Rev Mol Diagn 2021 Apr 19:1-11. Epub 2021 Apr 19.

Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: There is tremendous interest in the development of liquid biopsy techniques, but the potential role of liquid biopsy for the early detection of cancer has not yet been elucidated. We aim to explore the performance of liquid biopsy in the early diagnosis of cancer.

Methods: A systematic review was conducted of liquid biopsy in cancer early detection. Meta-regression was carried out to explore the source of heterogeneity and publication bias was also evaluated.

Results: Overall, there were six types of biomarkers and 17 studies focusing on liquid biopsy in the early detection of cancer, 7 studies in ctDNA, 5 studies in cfDNA, 2 studies in CTC, and the other three studies used circulating nucleosome, microRNA, and multiple biomarkers, respectively. Pooled sensitivity and specificity of liquid biopsy in cancer early detection was 0.76 (95%CI:0.67-0.83) and 0.92 (95%CI:0.86-0.96) and the area under the SROC curve was 0.91 (95%CI:0.88-0.93).

Conclusions: The current evidence shows that liquid biopsy has relatively low sensitivity and high specificity in cancer early detection. Among all these biomarkers, cfDNA may have potentially promising value in cancer early detection, thereby supporting further study of cancer early detection.

Study Registration: The study is registered at PROSPERO (Identifier number: CRD42020137205).
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http://dx.doi.org/10.1080/14737159.2021.1910025DOI Listing
April 2021

Improvement of ECM-based bioroot regeneration via N-acetylcysteine-induced antioxidative effects.

Stem Cell Res Ther 2021 Mar 22;12(1):202. Epub 2021 Mar 22.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Sec., Ren Min Nan Road, Chengdu, 610041, China.

Background: The low survival rate or dysfunction of extracellular matrix (ECM)-based engineered organs caused by the adverse effects of unfavourable local microenvironments on seed cell viability and stemness, especially the effects of excessive reactive oxygen species (ROS), prompted us to examine the importance of controlling oxidative damage for tissue transplantation and regeneration. We sought to improve the tolerance of seed cells to the transplant microenvironment via antioxidant pathways, thus promoting transplant efficiency and achieving better tissue regeneration.

Methods: We improved the antioxidative properties of ECM-based bioroots with higher glutathione contents in dental follicle stem cells (DFCs) by pretreating cells or loading scaffolds with the antioxidant NAC. Additionally, we developed an in situ rat alveolar fossa implantation model to evaluate the long-term therapeutic effects of NAC in bioroot transplantation.

Results: The results showed that NAC decreased HO-induced cellular damage and maintained the differentiation potential of DFCs. The transplantation experiments further verified that NAC protected the biological properties of DFCs by repressing replacement resorption or ankylosis, thus facilitating bioroot regeneration.

Conclusions: The following findings suggest that NAC could significantly protect stem cell viability and stemness during oxidative stress and exert better and prolonged effects in bioroot intragrafts.
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http://dx.doi.org/10.1186/s13287-021-02237-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986250PMC
March 2021

Natural Transformation of and Its Determinants.

Front Microbiol 2021 3;12:634895. Epub 2021 Mar 3.

Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

In a previous study, it was shown that , a member of , is naturally competent. However, whether natural competence is universal in remains unknown. In this study, it was shown for the first time that was naturally competent in the laboratory condition; however, was not naturally competent under the same conditions. The competence of was maintained throughout the growth phases, and the transformation frequency was highest during the logarithmic phase. A competition assay revealed that preferentially took up its own genomic DNA over heterologous DNA. The natural transformation frequency of was significantly increased in GCB medium without peptone or phosphate. Furthermore, natural transformation of was inhibited by 0.5 mM EDTA, but could be restored by the addition of CaCl, MgCl, ZnCl, and MnCl, suggesting that these divalent cations promote the natural transformation of . Overall, this study revealed that natural competence is not universal in members and triggering of competence differs from species to species.
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http://dx.doi.org/10.3389/fmicb.2021.634895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965970PMC
March 2021

Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety.

Infect Dis Poverty 2021 Mar 19;10(1):32. Epub 2021 Mar 19.

Department of Tuberculosis, The Second Affiliated Hospital of Hainan Medical University, Haikou, People's Republic of China.

Background: World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP).

Methods: AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort.

Results: By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1-2) and 33.1% as serious (Grade 3-5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75-169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually.

Conclusions: Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.
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http://dx.doi.org/10.1186/s40249-021-00819-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977294PMC
March 2021

Influence of lincomycin on anaerobic digestion: Sludge type, biogas generation, methanogenic pathway and resistance mechanism.

Bioresour Technol 2021 Jun 28;329:124913. Epub 2021 Feb 28.

Key Laboratory of Yangtze River Water Environment, College of Environmental Science and Engineering, Tongji University, 1239 Siping Road, Shanghai 200092, PR China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, PR China. Electronic address:

This study investigated the tolerance, defensive response and methanogenic pathways of anaerobic granular slugde and anaerobic suspended sludge (AGS and ASS) exposed to different LCM concentrations. AGS presented a higher tolerance to LCM stress, accompanied with 20.8 ± 2.6% enhancement in methane production at 1000 mg/L LCM, which was likely attributed to the less cell deaths and extracellular polymeric substances (EPSs) protection. In the acidification stage, acetate accumulation was stimulated and the activity of acetate kinase was promoted by LCM. In the methanogenesis stage, propionate and butyrate utilization for methane production were impaired after LCM addition. LCM also improved the activity of pyruvate-ferredoxin oxidoreductase and strengthened the process of hydrogenotrophic methanogenesis, likely by accelerating interspecies electron transfer mediated by hydrogen. ErmB and ermF were the dominate LCM resistance genes in AGS under LCM pressure conferring the resistance mechanism of ribosomal protection.
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http://dx.doi.org/10.1016/j.biortech.2021.124913DOI Listing
June 2021

Oxidative phosphorylation enhances the leukemogenic capacity and resistance to chemotherapy of B cell acute lymphoblastic leukemia.

Sci Adv 2021 Mar 10;7(11). Epub 2021 Mar 10.

Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

How metabolic status controls the fates of different types of leukemia cells remains elusive. Using a SoNar-transgenic mouse line, we demonstrated that B cell acute lymphoblastic leukemia (B-ALL) cells had a preference in using oxidative phosphorylation. B-ALL cells with a low SoNar ratio (SoNar-low) had enhanced mitochondrial respiration capacity, mainly resided in the vascular niche, and were enriched with more functional leukemia-initiating cells than that of SoNar-high cells in a murine B-ALL model. The SoNar-low cells were more resistant to cytosine arabinoside (Ara-C) treatment. cyclic adenosine 3',5'-monophosphate response element-binding protein transactivated pyruvate dehydrogenase complex component X and cytidine deaminase to maintain the oxidative phosphorylation level and Ara-C-induced resistance. SoNar-low human primary B-ALL cells also had a preference for oxidative phosphorylation. Suppressing oxidative phosphorylation with several drugs sufficiently attenuated Ara-C-induced resistance. Our study provides a unique angle for understanding the potential connections between metabolism and B-ALL cell fates.
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http://dx.doi.org/10.1126/sciadv.abd6280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946372PMC
March 2021

The Comprehensive Analyses of Genomic Variations and Assessment of TMB and PD-L1 Expression in Chinese Lung Adenosquamous Carcinoma.

Front Genet 2020 17;11:609405. Epub 2021 Feb 17.

Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

The poor prognosis and fewer treatment option is a current clinical challenge for patients with lung adenosquamous carcinoma (ASC). The previous studies reported that tumor mutational burden (TMB, numbers of mutation per Megabase) is a predictor of clinical response in trials of multiple cancer types, while fewer studies assessed the relationship between TMB level and clinical features and outcomes of lung ASC. Herein, the present study enrolled Chinese patients with lung ASC. DNA was extracted from formalin-fixed paraffin-embedded tumor samples and subjected to next generation sequencing (NGS), and the 457 cancer related genes were evaluated. The results demonstrated that 95 unique genes with somatic variations were identified in the enrolled patients. The top three of high frequency gene mutations were with rates of 62% (13 cases), 48% (10 cases), and 14% (3 cases), respectively. We identified TMB value was significantly correlated with pathological stages ( < 0.05) and invasion of lymph node ( < 0.05). However, TMB value was not significantly correlated to other clinicopathologic indexes, for examples, age, sex, smoking history, tumor size, as well as and mutations in lung ASC. Moreover, TMB value was associated with the overall survival ( < 0.01), but not with the relapse-free survival ( = 0.23). In conclusion, this study indicated that lung ASC with high TMB might be associated with the invasion of lymph node and short overall survival. Immunotherapy might be a promising treatment option for lung ASC patients with high TMB.
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http://dx.doi.org/10.3389/fgene.2020.609405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925901PMC
February 2021

The effects of LncRNA PVT1 on clinical characteristics and survival in breast cancer patients: A protocol for systematic review and meta analysis.

Medicine (Baltimore) 2021 Feb;100(8):e24774

Department of Hepatological surgery, China Resources Wisco General Hospital, Wuhan, China.

Background: Currently, an increasing number of long noncoding RNAs (LncRNAs) have been reported to be abnormally expressed in human carcinomas and play a vital role in tumourigenesis. Some studies were carried out to investigate the influence of the expression of plasmacytoma variant translocation 1 (PVT1) on prognosis and its clinical significance in patients with breast cancer, while the results were contradictory and uncertain. A meta-analysis was conducted with controversial data to accurately assess the issue.

Methods: A detailed search of relevant researches was performed in Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science. Two reviewers independently conducted data extraction and literature quality evaluation. Odd ratio and its 95% confidence intervals were applied to evaluate the relationship between PVT1 and clinicopathological characteristics of breast cancer patients. Hazard ratios and its 95% confidence intervals were adopted to assess the prognostic effects of PVT1 on overall survival and disease-free survival. Meta-analysis was conducted with Stata 14.0 software.

Results: This study will provide high-quality evidence-based medical evidence for the correlation between PVT1 expression and overall survival, and disease-free survival and clinicopathological features.

Conclusion: The study will provide updated evidence to evaluate whether the expression of PVT1 is in association with poor prognosis in patients with breast cancer.

Osf Registration Number: DOI 10.17605/OSF.IO/C2TYE.
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http://dx.doi.org/10.1097/MD.0000000000024774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909102PMC
February 2021

Clinical exome sequencing reveals a mutation in PDHA1 in Leigh syndrome: A case of a Chinese boy with lethal neuropathy.

Mol Genet Genomic Med 2021 Mar 4:e1651. Epub 2021 Mar 4.

Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, China.

Background: Leigh syndrome, the most common mitochondrial syndrome in pediatrics, has diverse clinical manifestations and is genetically heterogeneous. Pathogenic mutations in more than 75 genes of two genomes (mitochondrial and nuclear) have been identified. PDHA1 encoding the E1 alpha subunit is an X-chromosome gene whose mutations cause pyruvate dehydrogenase complex deficiency.

Methods: Here, we have described a 12-year-old boy with lethal neuropathy who almost died of a sudden loss of breathing and successive cardiac arrest. Extracorporeal membrane oxygenation rescued his life. His diagnosis was corrected from Guillain-Barré syndrome to Leigh syndrome 1 month later by clinical exome sequencing. Furthermore, we used software to predict the protein structure caused by frameshift mutations. We treated the boy with vitamin B1, coenzyme Q10, and a ketogenic diet.

Results: A PDHA1 mutation (NM_000284.4:c.1167_1170del) was identified as the underlying cause. The amino acid mutation was p.Ser390LysfsTer33. Moreover, the protein structure prediction results suggested that the protein structure has changed. The parents of the child were negative, so the mutation was de novo. The comprehensive assessment of the mutation was pathogenic. His condition gradually improved after receiving treatment.

Conclusion: This case suggests that gene detection should be popularized to improve diagnosis accuracy, especially in developing countries such as China.
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http://dx.doi.org/10.1002/mgg3.1651DOI Listing
March 2021

Effectiveness and safety of warm needle acupuncture on lumbar muscles strain: A protocol for systematic review and meta analysis.

Medicine (Baltimore) 2021 Mar;100(9):e24401

School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, China.

Background: Lumbar muscle strain (LMS) is the most common orthopedic syndrome, with high incidence globally and lingering disease, which seriously affects patients' work efficiency and quality of life. Warm needle acupuncture (WNA) is a treatment method combining acupuncture technology with warm and medicinal effect of moxibustion. It has outstanding curative effect and wide range of treatment, especially in the treatment of pain diseases. We aim to collect clinical evidence and demonstrate the efficacy and safety of WNA on LMS.

Methods/design: We will search the following database sources for the randomized controlled trials: PubMed, Cochrane Library, Excerpta Medica Database (EMBASE), Web of Science, WHO International Clinical Trials Registry Platform (TCTRP), Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Database (VIP), and the Wanfang Database.All randomized controlled trials of WNA for lumbar muscle strain (LMS) in the above database will be considered for inclusion, and high-quality articles will be screened for data extraction and analysis, to summarize the therapeutic effect of WNA on LMS patients.

Result: This study will provide a rational synthesis of current evidences for warm needle acupuncture on lumbar muscle strain.

Conclusion: The conclusion of this study will provide evidence to judge the effectiveness and safety of WNA on LMS.

Trial Registration: INPLASY2020120100 (DOI number: 10.37766/inplasy2020.12.0100).
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http://dx.doi.org/10.1097/MD.0000000000024401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939226PMC
March 2021

Comparative study of oncologic efficacy of cephalomedial to lateral dissection versus medial to lateral dissection in laparoscopic total mesorectal excision for rectal cancer: An RCT study.

J Surg Oncol 2021 May 1;123 Suppl 1:S65-S75. Epub 2021 Mar 1.

Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background And Objectives: We compared the 3-year overall survival between cephalomedial-to-lateral approach proctectomy (CEMP) and medial-to-lateral approach proctectomy (MAP) in patients undergoing laparoscopic total mesorectal excision for rectal cancer. The advantages of CEMP and the clinical value of No. 253 lymph nodes resection have not been objectively analyzed in literature.

Methods: This was a prospective, two-arm, multicenter, single-blinded, randomized trial. The primary endpoint was 3-year overall survival, and secondary endpoints included safety, feasibility, oncological radicality (including number of No. 253 lymph nodes harvested), short-term outcome, 3-year disease-free survival, rate of postoperative complications, mortality, and rate of recurrence.

Results: From May 2016 to July 2020, 506 patients were enrolled-256 in the CEMP group and 250 in the MAP group. Comparison of overall survival and disease-free survival showed that there was treatment benefit in the CEMP group (28.22 ± 12.12 vs. 27.44 ± 13.06, p = 0.485; 27.24 ± 12.01 vs. 26.42 ± 12.81; p = 0.457). More No. 253 lymph nodes were harvested in the CEMP group, and cases with positive No. 253 lymph nodes had worse prognosis in stage III. Surgical safety was equal for both approaches.

Conclusions: Dissection of No. 253 lymph nodes may be important to improve clinical prognosis, but further studies with larger samples are needed to confirm this finding.
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http://dx.doi.org/10.1002/jso.26425DOI Listing
May 2021

A microelectric cell sensing technique for in vitro assessment of ocular irritation.

Toxicol In Vitro 2021 Jun 23;73:105124. Epub 2021 Feb 23.

Alberta Centre for Toxicology, Department of Physiology & Pharmacology, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

The animal-based Draize test remains the gold standard for assessment of ocular irritation. However, subjective scoring methods, species differences, and animal welfare concerns have spurred development of alternative test methods. In this study, a novel in vitro method for assessing ocular irritancy was developed using a microelectric cell sensing technology, real-time cell analysis (RTCA). The cytotoxicity of sixteen compounds was assessed in two cell lines: ARPE-19 (human retina) and SIRC (rabbit cornea). In vitro inhibitory (IC and AUC) values were determined at 6, 12, 24, 48, 72, and 96 h exposure, with a subset of values confirmed with MTT testing. The values displayed comparable predictivity of in vivo ocular irritation on the basis of a linear regression between the calculated values and each compounds' corresponding Draize-determined modified maximum average score (MMAS), but the ARPE-19 derived values were more strongly correlated than those from SIRC cells. Hence, IC values derived from ARPE-19 cells were used to predict the UN GHS/EU CLP classification of each test compound. The method was determined to have sensitivity of 90%, specificity of 50%, and overall concordance of 75%. Thus, RTCA testing may be best incorporated into a top-down tiered testing strategy for identification of ocular irritants in vitro.
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http://dx.doi.org/10.1016/j.tiv.2021.105124DOI Listing
June 2021

Analysis of complete mitochondrial genome sequence of bar-tailed Treecreeper (psittaciformes: Certhiidae).

Mitochondrial DNA B Resour 2021 Feb 12;6(2):578-580. Epub 2021 Feb 12.

Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming, China.

Bar-tailed Treecreeper usually lives in coniferous or mixed broadleaf-conifer forests, often crawling along the trunk. In this study, we first sequenced and described the complete mitochondrial genome and phylogeny of . The whole genome of was 16,852 bp in length, and contained 13 protein-coding genes, 22 transfer RNA genes, 2 ribosome RNA genes, and 1 non-coding control regions. The overall base composition of the mitochondrial DNA was 25.1% for A, 29.2% for T, 14.5% for C, 31.2% for G, with a GC content of 45.7%. A phylogenetic tree strongly supported that closely related with Family Troglodytidae by highly probability.
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http://dx.doi.org/10.1080/23802359.2021.1875909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889127PMC
February 2021

Artificial Intelligence in Decision-Making for Colorectal Cancer Treatment Strategy: An Observational Study of Implementing Watson for Oncology in a 250-Case Cohort.

Front Oncol 2020 4;10:594182. Epub 2021 Feb 4.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Personalized and novel evidence-based clinical treatment strategy consulting for colorectal cancer has been available through various artificial intelligence (AI) supporting systems such as Watson for Oncology (WFO) from IBM. However, the potential effects of this supporting tool in cancer care have not been thoroughly explored in real-world studies. This research aims to investigate the concordance between treatment recommendations for colorectal cancer patients made by WFO and a multidisciplinary team (MDT) at a major comprehensive gastrointestinal cancer center.

Methods: In this prospective study, both WFO and the blinded MDT's treatment recommendations were provided concurrently for enrolled colorectal cancers of stages II to IV between March 2017 and January 2018 at Shanghai Minimally Invasive Surgery Center. Concordance was achieved if the cancer team's decisions were listed in the "recommended" or "for consideration" classification in WFO. A review was carried out after 100 cases for all non-concordant patients to explain the inconsistency, and corresponding feedback was given to WFO's database. The concordance of the subsequent cases was analyzed to evaluate both the performance and learning ability of WFO.

Results: Overall, 250 patients met the inclusion criteria and were recruited in the study. Eighty-one were diagnosed with colon cancer and 189 with rectal cancer. The concordances for colon cancer, rectal cancer, or overall were all 91%. The overall rates were 83, 94, and 88% in subgroups of stages II, III, and IV. When categorized by treatment strategy, concordances were 97, 93, 89, 87, and 100% for neoadjuvant, surgery, adjuvant, first line, and second line treatment groups, respectively. After analyzing the main factors causing discordance, relative updates were made in the database accordingly, which led to the concordance curve rising in most groups compared with the initial rates.

Conclusion: Clinical recommendations made by WFO and the cancer team were highly matched for colorectal cancer. Patient age, cancer stage, and the consideration of previous therapy details had a significant influence on concordance. Addressing these perspectives will facilitate the use of the cancer decision-support systems to help oncologists achieve the promise of precision medicine.
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http://dx.doi.org/10.3389/fonc.2020.594182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899045PMC
February 2021

Iron-based nanoparticles for MR imaging-guided ferroptosis in combination with photodynamic therapy to enhance cancer treatment.

Nanoscale 2021 Mar;13(9):4855-4870

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China.

Ferroptosis therapy, which applies ferroptotic inducers to produce lethal lipid peroxidation and induce the death of tumor cells, is regarded as a promising therapeutic strategy for cancer treatment. However, there is still a challenge regarding how to increase reactive oxygen species (ROS) accumulation in the tumor microenvironment (TME) to enhance antitumor efficacy. Herein, we designed a nanosystem coated with the FDA approved poly(lactic-co-glycolic acid) (PLGA) containing ferrous ferric oxide (Fe3O4) and chlorin E6 (Ce6) for synergistic ferroptosis-photodynamic anticancer therapy. The Fe3O4-PLGA-Ce6 nanosystem can dissociate in the acidic TME to release ferrous/ferric ions and Ce6. Then, the Fenton reaction between the released ferrous/ferric ions and intracellular excess hydrogen peroxide can occur to produce hydroxyl radicals (˙OH) and induce tumor cell ferroptosis. The released Ce6 can increase the generation and accumulation of ROS under laser irradiation to offer photodynamic therapy, which can boost ferroptosis in 4T1 cells. Moreover, magnetic monodisperse Fe3O4 loading provides excellent T2-weighted magnetic resonance imaging (MRI) properties. The Fe3O4-PLGA-Ce6 nanosystem possesses MRI ability and highly efficient tumor suppression with high biocompatibility in vivo due to the synergism of photodynamic and ferroptosis antitumor therapies.
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http://dx.doi.org/10.1039/d0nr08757bDOI Listing
March 2021

Association between sex hormones regulation-related SNP rs12233719 and lung cancer risk among never-smoking Chinese women.

Cancer Med 2021 03 17;10(5):1880-1888. Epub 2021 Feb 17.

Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: The mechanism of rapidly increased non-small cell lung cancer (NSCLC) among never-smoking Chinese women has not been elucidated. Ovarian sex steroid hormones have been suggested to counteract lung cancer development, and sex hormone-binding globulin (SHBG) is essential in sex hormones regulation. This study aims to exploring single nucleotide polymorphisms (SNPs) in genomic regions associated with SHBG concentrations that contributed to never-smoking female NSCLC.

Methods: Candidate genes were selected by a genome-wide association (GWAS) meta-analysis and gene expression profiles of never-smoking NSCLC of Chinese women. The candidate SNPs limited to common minor allele frequency (MAF), missense variant, ethnic heterogeneous distribution, and SNPs were genotyped using the TaqMan method. A two-stage case-control design was adopted for exploration and validation of associations between candidate SNPs and risk of NSCLC. All participants were never-smoking Chinese women. Chi-square test and multivariate logistic regression were applied.

Results: Beginning with 12 genomic regions associated with circulating SHBG concentrations and gene expression profiles from never-smoking NSCLC in Chinese women, candidate SNP rs12233719 and rs7439366 both located in candidate gene UGT B which may be related to circulating SHBG concentrations and cancer risk, were identified. A two-stage case-control study was conducted in Shenyang and Tianjin represented as the training stage and validation stage, respectively. Under the dominant model, compared to individuals with the wild G/G genotype, the adjusted OR of those with the T allele was 1.58 (95% CI: 1.15-2.16) in Chinese Shenyang training set, and was 1.49 (95% CI: 1.02-2.18) in Chinese Tianjin validation set, both accompanied with a significant trend relationship consistently. UGT2B7 was upregulated in female NSCLC patients' tumor tissues and was associated with a poor prognosis in NSCLC.

Conclusion: Our findings indicated that a sex hormones regulation-related SNP rs12233719 was associated with never-smoking female lung cancer risk, which might partially explain NSCLC-susceptibility in Chinese women.
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http://dx.doi.org/10.1002/cam4.3772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940208PMC
March 2021

Effect of public health interventions on COVID-19 cases: an observational study.

Thorax 2021 Feb 16. Epub 2021 Feb 16.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Background: As the epidemic of COVID-19 is gradually controlled in China, a summary of epidemiological characteristics and interventions may help control its global spread.

Methods: Data for COVID-19 cases in Hubei Province (capital, Wuhan) was extracted until 7 March 2020. The spatiotemporal distribution of the epidemic in four periods (before 10 January, 10-22 January, 23 January-6 February and 7 February-7 March) was evaluated, and the impacts of interventions were observed.

Results: Among 67 706 COVID-19 cases, 52 111 (76.97%) were aged 30-69 years old, and 34 680 (51.22%) were women. The average daily attack rates (95% CI) were 0.5 (0.3 to 0.7), 14.2 (13.2 to 15.1), 45.7 (44.0 to 47.5) and 8.6 (7.8 to 9.3) cases per 10 people in four periods, and the harmonic means (95% CI) of doubling times were 4.28 (4.01 to 4.55), 3.87 (3.78 to 3.98), 5.40 (4.83 to 6.05) and 45.56 (39.70 to 52.80) days. Compared with the first period, daily attack rates rose rapidly in the second period. In the third period, 14 days after 23 January, the daily average attack rate in and outside Wuhan declined by 33.8% and 48.0%; the doubling times increased by 95.0% and 133.2%. In the four periods, 14 days after 7 February, the daily average attack rate in and outside Wuhan decreased by 79.1% and 95.2%; the doubling times increased by 79.2% and 152.0%.

Conclusions: The public health interventions were associated with a reduction in COVID-19 cases in Hubei Province, especially in districts outside of Wuhan.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887867PMC
February 2021

hDPSC-laden GelMA microspheres fabricated using electrostatic microdroplet method for endodontic regeneration.

Mater Sci Eng C Mater Biol Appl 2021 Feb 6;121:111850. Epub 2021 Jan 6.

Engineering Research Center of Oral Translational Medicine, Ministry of Education, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address:

The microsphere system has attracted considerable attention as a stem-cell delivery vehicle in regeneration medicine owing to its injectability, fast substance transfer ability, and mimicry of the three-dimensional native environment. However, suitable biomaterials for preparation of microspheres optimal for endodontic regeneration are still being explored. Owing to its excellent bioactivity and biodegradability, gelatin methacryloyl (GelMA) was used to fabricate hydrogel microspheres by the electrostatic microdroplet method, and the potential of GelMA microspheres applied in endodontic regeneration was studied. The average size of GelMA microspheres encapsulating human dental pulp stem cells (hDPSCs) was ~200 μm, and the Young's modulus was approximately 582.8 ± 66.0 Pa, which was close to that of the natural human dental pulp. The encapsulated hDPSCs could effectively adhere, spread, proliferate, and secrete extracellular matrix proteins in the microspheres, and tended to occupy the outer layer. Moreover, the cell-laden GelMA microsphere system could withstand cryopreservation, and the thawed cells exhibited normal functions. After subcutaneous implantation in a nude mouse model, more vascularized pulp-like tissues were generated in the cell-laden GelMA microsphere group compared with that in the cell-laden bulk GelMA group, and this was accompanied by a suitable degradation rate. The GelMA microspheres showed remarkable performances and great potential as cell delivery vehicles in endodontic regeneration.
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http://dx.doi.org/10.1016/j.msec.2020.111850DOI Listing
February 2021