Publications by authors named "Ming Chen"

2,784 Publications

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Polyhydramnios as a sole ultrasonographic finding for detecting fetal hemolytic anemia caused by anti-c alloimmunization.

Taiwan J Obstet Gynecol 2022 Jul;61(4):722-725

Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan; Department of Genomic Medicine, Changhua Christian Hospital, Changhua, Taiwan; Department of Obstetrics and Gynecology, College of Medicine, and Hospital, National Taiwan University, Taipei, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan; Department of Biomedical Science, Dayeh University, Changhua, Taiwan. Electronic address:

Objective: The prenatal course of a rare case with fetal anemia caused by maternal anti-c alloimmunization was reported.

Case Report: A 39-year-old female with anti-c and anti-E antibodies against red cells had previously experienced a stillbirth. At her present pregnancy, titers of maternal antibodies and fetal middle cerebral artery peak systolic velocity (MCA-PSV) were frequently monitored to investigate the severity of fetal hemolytic anemia. Rather than manifesting as an increase in MCA-PSV, the anemic fetus was delivered at 32 weeks and one day of gestation with a sole presentation: polyhydramnios. Neonatal hospitalization course were compatible with hemolytic anemia. The baby was discharged at 48 days of age.

Conclusion: This case illustrated the complexities of dealing with maternal red cell alloimmunization during pregnancy and the limitations of noninvasive diagnostic modalities for detecting fetal anemia, and highlighted that obstetricians should refer all available clinical parameters in order to offer appropriate perinatal care.
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http://dx.doi.org/10.1016/j.tjog.2022.04.006DOI Listing
July 2022

Reproductive outcomes of cesarean scar pregnancies treated with uterine artery embolization combined with curettage.

Taiwan J Obstet Gynecol 2022 Jul;61(4):601-605

Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan; NUWA Fertility Center, Taichung, Taiwan; School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Objective: The aim of this study was to review the reproductive outcomes of women with a cesarean scar pregnancy (CSP) treated with dilation and curettage (D&C) after uterine artery embolization (UAE).

Materials And Methods: This was a retrospective study to review women who received UAE followed by D&C for CSP between January 2010 and December 2019 at the Changhua Christian Hospital, Changhua in Taiwan. Data were collected from both electronic and paper medical records. Patients were contact via phone call to follow up reproductive outcomes between January 2021 and March 2021. These subsequent reproductive outcomes (including pregnancy rate, secondary infertility rate, miscarriage rate, live birth rate, and recurrent CSP rate) were recorded and analyzed.

Results: A total of 53 cases of women who received UAE followed by D&C for CSP were identified. The women's average age was 34.8 ± 5.1 years. The mean gestational age at diagnosis was 6.2 ± 1.1 weeks. The mean level for human chorionic gonadotropin was 23,407.7 ± 29,105.5 mIU/ml. The average of blood loss during D&C was 19.2 ± 43.6 ml. The average hospitalization time after D&C was 3.5 ± 1.1 days. Of the 53 cases, 10 patients were lost to follow-up and 43 patients agreed to follow-up on reproductive outcomes in 2021. Twenty-three patients who desired to conceive were analyzed. Nineteen out of these 23 women (82.6%) succeeded in conceiving again and gave birth to 15 healthy babies (78.9%). Only one woman (1/19, 5.3%) experienced recurrence of CSP. The average time interval between previous CSP treatment and subsequent conception was 10.4 ± 6.7 months.

Conclusion: UAE combined with curettage treatment in CSP patients results in a positive rate of subsequent pregnancy outcomes. This minimally invasive procedure may be considered as one of the treatment options for CSP, as it enables preservation of fertility after treatment.
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http://dx.doi.org/10.1016/j.tjog.2021.08.005DOI Listing
July 2022

Neutrophils as regulators of macrophage-induced inflammation in a setting of allogeneic bone marrow transplantation.

Stem Cell Reports 2022 Jun 12. Epub 2022 Jun 12.

Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China. Electronic address:

Clinical data reveal that patients with allogeneic hematopoietic stem cell transplantation (HSCT) are vulnerable to infection and prone to developing severe sepsis, which greatly compromises the success of transplantation, indicating a dysregulation of inflammatory immune response in this clinical setting. Here, by using a mouse model of haploidentical bone marrow transplantation (haplo-BMT), we found that uncontrolled macrophage inflammation underlies the pathogenesis of both LPS- and E.coli-induced sepsis in recipient animals with graft-versus-host disease (GVHD). Deficient neutrophil maturation in GVHD mice post-haplo-BMT diminished modulation of macrophage-induced inflammation, which was mechanistically dependent on MMP9-mediated activation of TGF-β1. Accordingly, adoptive transfer of mature neutrophils purified from wild-type donor mice inhibited both sterile and infectious sepsis in GVHD mice post-haplo-BMT. Together, our findings identify a novel mature neutrophil-dependent regulation of macrophage inflammatory response in a haplo-BMT setting and provide useful clues for developing clinical strategies for patients suffering from post-HSCT sepsis.
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http://dx.doi.org/10.1016/j.stemcr.2022.05.021DOI Listing
June 2022

Circ_0061395 functions as an oncogenic gene in hepatocellular carcinoma by acting as a miR-1182 sponge.

Cell Cycle 2022 Jul 1:1-14. Epub 2022 Jul 1.

The First Affiliated Hospital, Department of Gastroenterology and Hepatology, Hengyang Medical School, University of South China, Hengyang City, Hunan Province, China.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in liver cancer, with a high rate of metastasis and recurrence. Circular RNA_0061395 (circ_0061395) has been shown to be involved in the advance of HCC. However, the interaction between circ_0061395 and microRNA (miRNA) in HCC has not been studied. Quantitative real-time polymerase-chain reaction (qRT-PCR) was used to detect the expression of related genes in liver cancer tissues and cells. The stability of circ_0061395 was verified by RNase R digestion. Through detection of cell malignant behavior and apoptosis, the capping experiment was carried out to verify the regulatory relationship between miR-1182 and circ_0061395 or SPARC/osteonectin, CWCV and Kazal-like domains proteoglycan 1 (SPOCK1). The expression of related proteins was detected by western blot. The interaction of miR-1182 with circ_0061395 or SPOCK1 has been notarized by Dual-luciferase reporter analysis and RNA immunoprecipitation (RIP) assay. Xenotransplantation experiments using BALB/C nude mice were used to confirm the function of circ_0061395 . Circ_0061395 and SPOCK1 were significantly expressed in liver cancer tissues and cells. Silencing circ_0061395 reduced the proliferation, migration, invasion, tube formation and tumor spheroid formation rate of Huh-7 and SNU-387 cells. MiR-1182 was a target of circ_0061395. Silencing circ_0061395 inhibited the malignant behavior of HCC cells by releasing miR-1182. In addition, SPOCK1 was the target of miR-1182. Overexpression of SPOCK1 partially restored the inhibitory effect of miR-1182 on cell proliferation. Animal experiments confirmed the anti-tumor effect of silence circ_0061395. Circ_0061395 induced the changes of the expression of SPOCK1 by regulating miR-1182, thereby mediating the process of HCC, and at least partially promoting the development of HCC cells, providing a novel targeted therapy for HCC.
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http://dx.doi.org/10.1080/15384101.2022.2092177DOI Listing
July 2022

Childhood antibiotics as a risk factor for Crohn's disease: The ENIGMA International Cohort Study.

JGH Open 2022 Jun 1;6(6):369-377. Epub 2022 Jun 1.

Department of Medicine and Therapeutics, Institute of Digestive Disease The Chinese University of Hong Kong Shatin Hong Kong.

Background And Aim: Environmental factors play a key role in development of Crohn's disease (CD), thought to be mediated by changes in the gut microbiota. We aimed to delineate the potential contribution of antibiotic exposure to subsequent development of CD, across diverse geographical populations.

Methods: This case-control study in Australia and three cities in China (Hong Kong, Guangzhou, and Kunming) included four groups: patients with CD, at-risk individuals including non-affected first-degree relatives (FDRs) and household members of CD patients (HM), and unrelated healthy controls (HCs). Environmental risk factors, including childhood antibiotic use and 13 other categories, were assessed using a self-developed questionnaire. Logistic regression and conditional logistic regression were used to determine environmental factors associated with CD development.

Results: From 2017 to 2019, a total of 254 patients with CD (mean age: 37.98 ± 13.76 years; 58.3% male), 73 FDR (mean age: 49.35 ± 13.28 years; 46.6% male), 122 HMs (including FDR) (mean age: 45.50 ± 13.25 years; 47.5% male), and 78 HC (mean age: 45.57 ± 11.24; 47.4% male) were included. Comparing CD patients with their FDR and HMs, antibiotic use before 18 years old was a risk factor for CD development (adjusted odds ratio [OR] 3.46, 95% confidence interval [CI] 1.38-8.69;  = 0.008). There were no significant differences in other childhood environmental risk factors between CD and their FDR or HMs. Subgroup analysis showed that antibiotic use <18 years old was a risk factor for CD development in the Chinese (adjusted OR 4.80, 95% CI 1.62-12.24;  = 0.005) but not in Australian populations (OR 1.80, 95% CI 0.33-9.95;  = 0.498).

Conclusion: Use of antibiotics <18 years was a risk factor for CD development. Attention should be paid to identifying modifiable environmental risk factors in early childhood, especially in at-risk families.
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http://dx.doi.org/10.1002/jgh3.12755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218523PMC
June 2022

Corrigendum to "Bone marrow mononuclear cells exert long-term neuroprotection in a rat model of ischemic stroke by promoting arteriogenesis and angiogenesis" [Brain Behav. Immun. 34 (2013) 56-66].

Brain Behav Immun 2022 Jun 27;104:213-214. Epub 2022 Jun 27.

Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. Electronic address:

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http://dx.doi.org/10.1016/j.bbi.2022.04.025DOI Listing
June 2022

AIE-based gold nanostar-berberine dimer nanocomposites for PDT and PTT combination therapy toward breast cancer.

Nanoscale 2022 Jun 30. Epub 2022 Jun 30.

NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, China.

We designed and synthesized three new berberine-based compounds, namely, pyridine-2,6-dimethyl-/2,2'-bipyridine-3,3'-dimethyl-tethered berberine dimers BD1 and BD2, and a tetrakis(4-benzyl)ethylene linked berberine tetramer BD4. We identified that the dimer BD2 and tetramer BD4, as well as 1,10-phenanthroline-2,9-dimethyl-linked berberine dimer BD3 previously reported by us, showed remarkable aggregation-induced emission (AIE) properties which endowed them with higher singlet oxygen (O) production ability than berberine. Of the four compounds, BD3 exhibits the lowest Δ energy with the highest O generation ability and thus was selected for further construction of [email protected] (denoted as ABH, AuNSs = gold nanostars; HA = hyaluronic acid). The nanosystem of ABH shows a remarkable therapeutic effect toward breast cancer by combining photodynamic therapy (PDT) from BD3, photothermal therapy (PTT) from AuNSs, and the CD44-targeting capability of HA. The synergistically enhanced PDT and PTT induce superior cancer cell apoptosis/necrosis and anti-breast cancer activity . This study provides a new concept for PDT using natural product derivatives and their combination with PTT for efficient treatment of tumors.
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http://dx.doi.org/10.1039/d2nr03408eDOI Listing
June 2022

Rapid growth of Moso bamboo (Phyllostachys edulis): Cellular roadmaps, transcriptome dynamics, and environmental factors.

Plant Cell 2022 Jun 29. Epub 2022 Jun 29.

Co-Innovation Center for Sustainable Forestry in Southern China, Bamboo Research Institute, Key Laboratory of National Forestry and Grassland Administration on Subtropical Forest Biodiversity Conservation, College of Biology and the Environment, Nanjing Forestry University, Nanjing, Jiangsu 210037, China.

Moso bamboo (Phyllostachys edulis) shows remarkably rapid growth (114.5 cm/d), but the underlying biological mechanisms remain unclear. After examining >12,750 internodes from >510 culms from 17 Moso populations, we identified internode 18 as a representative internode for rapid growth. This internode includes a 2-cm cell division zone, a cell elongation zone up to 12-cm, and a secondary cell wall (SCW) thickening zone. These zones elongated 11.8 cm, produced ∼570,000,000 cells, and deposited ∼28 mg g-1 dry weight (DW) lignin and ∼44 mg g-1 DW cellulose daily, far exceeding vegetative growth observed in other plants. We used anatomical, mathematical, physiological, and genomic data to characterize development and transcriptional networks during rapid growth in internode 18. Our results suggest that 1) gibberellin may directly trigger the rapid growth of Moso shoots, 2) decreased cytokinin and increased auxin accumulation may trigger cell division zone elongation, and 3) abscisic acid and mechanical pressure may stimulate rapid SCW thickening via MYB83L. We conclude that internode length involves a possible trade-off mediated by mechanical pressure caused by rapid growth, possibly influenced by environmental temperature and regulated by genes related to cell division and elongation. Our results provide insight into the rapid growth of Moso bamboo.
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http://dx.doi.org/10.1093/plcell/koac193DOI Listing
June 2022

A novel hypoxic lncRNA, HRL-SC, promotes the proliferation and migration of human dental pulp stem cells through the PI3K/AKT signaling pathway.

Stem Cell Res Ther 2022 Jun 28;13(1):286. Epub 2022 Jun 28.

Shenzhen Stomatology Hospital (Pingshan), Southern Medical University, Shenzhen, 510515, Guangdong, People's Republic of China.

Background: Human dental pulp stem cells (hDPSCs) are critical for pulp generation. hDPSCs proliferate faster under hypoxia, but the mechanism by which long noncoding RNA (lncRNA) regulates this process is not fully understood.

Methods: Novel lncRNAs were obtained by reanalysis of transcriptome datasets from RNA-Seq under hypoxia compared with normoxia, and a differential expression analysis of target genes was performed. Bioinformatics analyses, including gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and gene set enrichment analysis, were used to understand the function of key novel lncRNAs. hDPSCs were isolated from dental pulp tissue. EdU and scratch wound healing assays were used to detect the proliferation and migration of hDPSCs. qRT-PCR was used to detect changes in the RNA expression of selected genes. RNA fluorescence in situ hybridization, small interfering RNA, qRT-PCR and Western blot analysis were used to explore the function of key novel lncRNAs.

Results: We identified 496 novel lncRNAs in hDPSCs under hypoxia, including 45 differentially expressed novel lncRNAs. Of these, we focused on a key novel lncRNA, which we designated HRL-SC (hypoxia-responsive lncRNA in stem cells). Functional annotation revealed that HRL-SC was associated with hypoxic conditions and the PI3K/AKT signaling pathway. HRL-SC was mainly located in the cytoplasm of hDPSCs and had stable high expression under hypoxia. Knockdown of HRL-SC inhibited the proliferation and migration of hDPSCs and the expression levels of PI3K/AKT-related marker proteins. Furthermore, the AKT activator SC79 partially offset the inhibitory effect caused by the knockdown, indicating that HRL-SC promoted hDPSCs through the PI3K/AKT signaling pathway.

Conclusions: Hypoxia-responsive lncRNA HRL-SC promotes the proliferation and migration of hDPSCs through the PI3K/AKT signaling pathway, and this understanding may facilitate the regenerative application of hDPSCs.
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http://dx.doi.org/10.1186/s13287-022-02970-5DOI Listing
June 2022

Study on Molecular Information Intelligent Diagnosis and Treatment of Bladder Cancer on Pathological Tissue Image.

Front Med (Lausanne) 2022 3;9:838182. Epub 2022 Jun 3.

Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Molecular information about bladder cancer is significant for treatment and prognosis. The immunohistochemistry (IHC) method is widely used to analyze the specific biomarkers to determine molecular subtypes. However, procedures in IHC and plenty of reagents are time and labor-consuming and expensive. This study established a computer-aid diagnosis system for predicting molecular subtypes, p53 status, and programmed death-ligand 1 (PD-L1) status of bladder cancer with pathological images.

Materials And Methods: We collected 119 muscle-invasive bladder cancer (MIBC) patients who underwent radical cystectomy from January 2016 to September 2018. All the pathological sections are scanned into digital whole slide images (WSIs), and the IHC results of adjacent sections were recorded as the label of the corresponding slide. The tumor areas are first segmented, then molecular subtypes, p53 status, and PD-L1 status of those tumor-positive areas would be identified by three independent convolutional neural networks (CNNs). We measured the performance of this system for predicting molecular subtypes, p53 status, and PD-L1 status of bladder cancer with accuracy, sensitivity, and specificity.

Results: For the recognition of molecular subtypes, the accuracy is 0.94, the sensitivity is 1.00, and the specificity is 0.909. For PD-L1 status recognition, the accuracy is 0.897, the sensitivity is 0.875, and the specificity is 0.913. For p53 status recognition, the accuracy is 0.846, the sensitivity is 0.857, and the specificity is 0.750.

Conclusion: Our computer-aided diagnosis system can provide a novel and simple assistant tool to obtain the molecular subtype, PD-L1 status, and p53 status. It can reduce the workload of pathologists and the medical cost.
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http://dx.doi.org/10.3389/fmed.2022.838182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9215327PMC
June 2022

Endosomal-Lysosomal and Autophagy Pathway in Alzheimer's Disease: A Systematic Review and Meta-Analysis.

J Alzheimers Dis 2022 Jun 23. Epub 2022 Jun 23.

Sandra Black Centre for Brain Resilience and Recovery, Sunnybrook Research Institute, Toronto, Ontario, Canada.

Background: The endosomal-lysosomal and autophagy (ELA) pathway may be implicated in the progression of Alzheimer's disease (AD); however, findings thus far have been inconsistent.

Objective: To systematically summarize differences in endosomal-lysosomal and autophagy proteins in the cerebrospinal fluid (CSF) of people with AD and healthy controls (HC).

Methods: Studies measuring CSF concentrations of relevant proteins in the ELA pathway in AD and healthy controls were included. Standardized mean differences (SMD) with 95% confidence intervals (CI) between AD and healthy controls in CSF concentrations of relevant proteins were meta-analyzed using random-effects models.

Results: Of 2,471 unique studies, 43 studies were included in the systematic review and meta-analysis. Differences in ELA protein levels in the CSF between AD and healthy controls were observed, particularly in lysosomal membrane (LAMP-1: NAD/NHC = 348/381, SMD [95% CI] = 0.599 [0.268, 0.930], I2 = 72.8% ; LAMP-2: NAD/NHC = 401/510, SMD [95% CI] = 0.480 [0.134, 0.826], I2 = 78.7%) and intra-lysosomal proteins (GM2A: NAD/NHC = 390/420, SMD [95% CI] = 0.496 [0.039, 0.954], I2 = 87.7% ; CTSB: NAD/NHC = 485/443, SMD [95% CI] = 0.201 [0.029, 0.374], I2 = 28.5% ; CTSZ: NAD/NHC = 535/820, SMD [95% CI] = -0.160 [-0.305, -0.015], I2 = 24.0%) and in proteins involved in endocytosis (AP2B1:NAD/NHC = 171/205, SMD [95% CI] = 0.513 [0.259, 0.768], I2 = 27.4% ; FLOT1: NAD/NHC = 41/45, SMD [95% CI] = -0.489 [-0.919, -0.058], I2 <0.01). LC3B, an autophagy marker, also showed a difference (NAD/NHC = 70/59, SMD [95% CI] = 0.648 [0.180, 1.116], I2 = 38.3%)), but overall there was limited evidence suggesting differences in proteins involved in endosomal function and autophagy.

Conclusion: Dysregulation of proteins in the ELA pathway may play an important role in AD pathogenesis. Some proteins within this pathway may be potential biomarkers for AD.
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http://dx.doi.org/10.3233/JAD-220360DOI Listing
June 2022

Asynchronous Space-Time-Coding Digital Metasurface.

Adv Sci (Weinh) 2022 Jun 25:e2200106. Epub 2022 Jun 25.

Institute of Electromagnetic Space, Southeast University, Nanjing, 210096, P. R. China.

Recent progress in space-time-coding digital metasurface (STCM) manifests itself a powerful tool to engineer the properties of electromagnetic (EM) waves in both space and time domains, and greatly expands its capabilities from the physical manipulation to information processing. However, the current studies on STCM are focused under the synchrony frame, namely, all meta-atoms follow the same variation frequency. Here, an asynchronous STCM is proposed, where the meta-atoms are modulated by different time-coding periods. In the proposed asynchronous STCM, the phase discontinuities on traditional metasurface are replaced with the frequency discontinuities. It is shown that dynamic wavefronts can be automatically realized for both fundamental and high-order harmonics by elaborately arranging the spatial distribution of meta-atoms with various time-coding periods. The physics insight is due to the accumulated rapidly changing phase difference with time, which offers an additional degree of freedom during the wave-matter interactions. As a proof-of-principle example, an asynchronous STCM for automatic spatial scanning and dynamic scattering control is investigated. From the theory, numerical simulations, and experiments, it can be found that the proposed STCM exhibits significant potentials for applications in radars and wireless communications.
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http://dx.doi.org/10.1002/advs.202200106DOI Listing
June 2022

Plant Biology and Biotechnology: Focus on Genomics and Bioinformatics.

Int J Mol Sci 2022 Jun 17;23(12). Epub 2022 Jun 17.

Department of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.

The study of molecular mechanisms of plant stress response is important for agrobiotechnology applications as it was discussed at series of recent bioinformatics conferences [...].
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http://dx.doi.org/10.3390/ijms23126759DOI Listing
June 2022

SGFNNs: Signed Graph Filtering-based Neural Networks for Predicting Drug-Drug Interactions.

J Comput Biol 2022 Jun 20. Epub 2022 Jun 20.

Department of Computer Science, Georgia State University, Atlanta, Georgia, USA.

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http://dx.doi.org/10.1089/cmb.2022.0113DOI Listing
June 2022

Robot-Assisted Laparoscopic Radical Cystectomy and Modified Y-Shaped Ileal Orthotopic Neobladder Reconstruction.

Front Surg 2022 1;9:889536. Epub 2022 Jun 1.

Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.

Background: Orthotopic neobladder reconstruction has become the preferred method of urinary diversion after radical cystectomy in major medical centers. We performed modified Y-shaped ileal orthotopic neobladder reconstruction and presented the functional results and postoperative complications of the modified surgery.

Methods: We included 21 patients with bladder cancer who underwent radical cystectomy at our center between February 2019 and December 2019. All patients underwent robotic-assisted laparoscopic radical cystectomy and lymph node dissection plus modified Y-shaped ileal orthotopic neobladder reconstruction. We collected the demographic and pathological history of the patients, and perioperative and postoperative functional outcomes and postoperative complications were recorded.

Results: All surgeries were successful and no serious postoperative complications occurred. The mean operative time was 321.43 ± 54.75 min, including 101.67 ± 10.88 min required for neobladder reconstruction. Liquid intake was encouraged about 5 days after surgery, stent and catheter were removed after 13.52 ± 3.28 days, and the patients were discharged 1-2 days after removing the catheter. No ureteral anastomotic and neobladder urethral anastomotic strictures occurred. The volume of the neobladder at 1-year post-surgery was 195.24 ± 16.07 mL and the maximum urinary flow rate was 20.64 ± 2.22 mL/s.

Conclusion: We describe the robotic-assisted modified Y-shaped ileal orthotopic neobladder reconstruction performed at our center, which requires a simple suture and short neobladder construction time, minimizes the occurrence of anastomotic stenosis, facilitates smooth patient emptying, and is clinically scalable and applicable.
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http://dx.doi.org/10.3389/fsurg.2022.889536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198462PMC
June 2022

Biological Efficacy Comparison of Natural Tussah Silk and Mulberry Silk Nanofiber Membranes for Guided Bone Regeneration.

ACS Omega 2022 Jun 31;7(23):19979-19987. Epub 2022 May 31.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China.

Biopolymer nanofiber membranes are attracting interest as promising biomaterial scaffolds with a remarkable range of structural and functional performances for guided bone regeneration (GBR). In this study, tussah silk nanofiber (TSn) and silk nanofiber (BSn) membranes were prepared by physical shearing. The diameters of the TSn and BSn membranes were 146.09 ± 63.56 and 120.99 ± 91.32 nm, respectively. TSn showed a Young's modulus of 3.61 ± 0.64 GPa and a tensile strength of 74.27 ± 5.19 MPa, which were superior to those of BSn, with a Young's modulus of 0.16 ± 0.03 GPa and a tensile strength of 4.86 ± 0.61 MPa. The potential of TSn and BSn membranes to guide bone regeneration was explored. In vitro, the TSn membrane exhibited significantly higher cell proliferation for MC3T3-E1 cells than the BSn membrane. In a cranial bone defect in a rat model, the TSn and BSn membranes displayed superior bone regeneration compared to the control because the membrane prevented the ingrowth of soft tissue to the defective area. Compared to the BSn membrane, the TSn membrane improved damaged bone regeneration, presumably due to its superior mechanical properties, high osteoconductivity, and increased cell proliferation. The TSn membrane has a bionic structure, excellent mechanical properties, and greater biocompatibility, making it an ideal candidate for GBR.
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http://dx.doi.org/10.1021/acsomega.2c01784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202271PMC
June 2022

Patchouli Alcohol Inhibits D-Gal Induced Oxidative Stress and Ameliorates the Quality of Aging Cartilage via Activating the Nrf2/HO-1 Pathway in Mice.

Oxid Med Cell Longev 2022 8;2022:6821170. Epub 2022 Jun 8.

Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, China.

Chondrocytes play an essential role in maintaining the structure and function of articular cartilage. Oxidative stress occurred in chondrocytes accelerates cell senescence and death, which contributes to the development of osteoarthritis (OA). Patchouli alcohol (PA), a kind of sesquiterpene in , processes multiple bioactivities in treatment of many diseases. However, its effects of antisenescence and antioxidation on chondrocytes in a D-gal-induced aging mice model are still obscure. In this study, we found that PA treatment could ameliorate the degradation of cartilage extracellular matrix (ECM) in a D-gal-induced aging mice model. Further analyses through the immunofluorescent staining and western blot revealed that PA inhibited D-gal-induced chondrocyte senescence via the activation of antioxidative system. Besides, the damage caused by D-gal could not be recovered with PA treatment in Nrf2-silencing chondrocytes. In addition, molecular docking analysis between PA and Keap1 further suggested that the mechanism of PA's antisenescence and antioxidation was attributed to the activation of Nrf2/HO-1 pathway. Therefore, our results demonstrated that PA was a promising candidate for preventing the quality loss of aging cartilage through inhibiting oxidative stress-mediated senescence in chondrocytes.
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http://dx.doi.org/10.1155/2022/6821170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200550PMC
June 2022

School Psychological Environment and Learning Burnout in Medical Students: Mediating Roles of School Identity and Collective Self-Esteem.

Front Psychol 2022 2;13:851912. Epub 2022 Jun 2.

School of Biomedical Engineering, Anhui Medical University, Hefei, China.

Learning burnout is an important indicator that reflects an individual's learning state. Understanding the influencing factors and mechanism of learning burnout of medical students has practical significance for improving their mental health. This study aimed to explore the mediating roles of school identity and collective self-esteem between school psychological environment and learning burnout in medical students. A total of 2,031 medical students (942 men and 1,089 women, age range: 17-23 years) were surveyed using the School Psychological Environment Questionnaire (SPEQ), School Identity Questionnaire (SIQ), Collective Self-esteem Scale (CSES), and Learning Burnout Scale (LBS). The results showed the following: (1) school psychological environment had a negative effect on learning burnout among medical students (β = -0.19, < 0.001), and (2) school identity and collective self-esteem played significant mediating roles between school psychological environment and learning burnout [95% CI = (-0.43, -0.31)]. Specifically, there were three paths that school psychological environment and learning burnout: first, through the independent mediating role of school identity; second, through the independent mediating role of collective self-esteem; and third, through the chain mediating roles of school identity and collective self-esteem. The findings reveal that school psychological environment not only directly influences the learning burnout of medical students but also indirectly influences it through school identity and collective self-esteem. Thus, this study has some important implications for prevention and intervention of learning burnout among medical students.
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http://dx.doi.org/10.3389/fpsyg.2022.851912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200954PMC
June 2022

Mitogen-activated protein kinase TaMPK3 suppresses ABA response by destabilizing TaPYL4 receptor in wheat.

New Phytol 2022 Jun 20. Epub 2022 Jun 20.

Institute of Crop Science, Chinese Academy of Agricultural Sciences (CAAS)/National Key Facility for Crop Gene Resources and Genetic Improvement, Key Laboratory of Biology and Genetic Improvement of Triticeae Crops, Ministry of Agriculture, Beijing, 100081, China.

Abscisic acid (ABA) receptors are considered as the targeted manipulation of ABA sensitivity and water productivity in plants. Regulation of their stability or activity will directly affect ABA signaling. Mitogen-activated protein kinase (MAPK) cascades link multiple environmental and plant developmental cues. However, the molecular mechanism of ABA signaling and MAPK cascade interaction remains largely elusive. TaMPK3 overexpression decreases drought tolerance and wheat sensitivity to ABA, significantly weakening ABA's inhibitory effects on growth. Under drought stress, overexpression lines show lower survival rates, shoot fresh weight, and proline content, but higher malondialdehyde (MDA) levels at seedling stage, as well as decreased grain width and thousand grain weight in both greenhouse and field conditions at the adult stage. TaMPK3-RNAi increases drought tolerance. TaMPK3 interaction with TaPYL4 leads to decreased TaPYL4 levels by promoting its ubiquitin-mediated degradation, while ABA treatment diminishes TaMPK3-TaPYL interactions. In addition, the expression of ABA signaling proteins is impaired in TaMPK3-overexpressing wheat plants under ABA treatment. The MPK3-PYL interaction module was found to be conserved across monocots and dicots. Our results suggest that the MPK3-PYL module could serve as a negative regulatory mechanism for balancing appropriate drought stress response with normal plant growth signaling in wheat.
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http://dx.doi.org/10.1111/nph.18326DOI Listing
June 2022

Ultrafast oxidative desulfurization of diesel fuel catalyzed by a polyoxometalate-based catalyst immobilized on functionalized Y-SBA-15.

Dalton Trans 2022 Jun 27;51(25):9864-9877. Epub 2022 Jun 27.

Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education, Key Laboratory of Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Chemical Reactor and Green Chemical Technology, Wuhan Institute of Technology, Wuhan 430073, P. R. China.

Y-SBA-15 was synthesized by doping yttrium (Y) into SBA-15 using a solvent-free solid-state grinding method, and 1-butyl-3-methylimidazolium phosphomolybdic salt ([Bmim]PMoO, abbreviated as [Bmim]PMoO) was also synthesized. [Bmim]PMoO/Y-SBA-15 was prepared and used for oxidative desulfurization (ODS). The physicochemical characteristics of the catalyst have been characterized by FT-IR, XRD, N adsorption-desorption, FESEM, TEM, XPS, contact angle testing, EPR, . A lipophilic surface is beneficial for making the catalyst well disperse in an oil phase, and a hydrophilic core can help to store aqueous oxidants. Therefore, the amphiphilic catalyst 25[Bmim]PMoO/10Y-SBA-15 exhibited high catalytic activity in dibenzothiophene (DBT) ODS, and sulfur compounds can be removed completely within 40 min under the following conditions: = 10 mL, = 0.1 g,  :  = 25%, and O/S = 4 (molar ratio). In addition, the concentration of aromatics exerted little effect on the DBT ODS. Sulfur compounds in real diesel might be reduced to 8 μg g. The hydroxyl radical ˙OH and superoxide radical ˙O play crucial roles in the ODS reaction, and the ODS reaction mechanism was also proposed.
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http://dx.doi.org/10.1039/d2dt00911kDOI Listing
June 2022

Programming a DNA tetrahedral nanomachine as an integrative tool for intracellular microRNA biosensing and stimulus-unlocked target regulation.

Mater Today Bio 2022 Jun 6;15:100276. Epub 2022 May 6.

Department of Clinical Laboratory Medicine, Southwest Hospital, Army Medical University, 30 Gaotanyan, Shapingba District, Chongqing, 400038, China.

The synchronous detection and regulation of microRNAs (miRNAs) are essential for the early tumor diagnosis and treatment but remains a challenge. An integrative DNA tetrahedral nanomachine was self-assembled for sensitive detection and negative feedback regulation of intracellular miRNAs. This nanomachine comprised a DNA tetrahedron nanostructure as the framework, and a miRNA inhibitor-controlled allosteric DNAzyme as the core. The DNA tetrahedron brought the DNAzyme and the substrate in spatial proximity and facilitated the cellular uptake of DNAzyme. In allosteric regulation of DNAzyme, the locked tetrahedral DNAzyme (L-tetra-D) and active tetrahedral DNAzyme (A-Tetra-D) were controlled by miRNA inhibitor. The combination of miRNA inhibitor and target could trigger the conformational change from L-tetra-D to A-Tetra-D. A-Tetra-D cleaved the substrate and released fluorescence for intracellular miRNA biosensing. The DNA tetrahedral nanomachine showed excellent sensitivity (with detection limit down to 0.77 pM), specificity (with one-base mismatch discrimination), biocompatibility and stability. Simultaneously, miRNA stimulus-unlocked inhibitor introduced by our nanomachine exhibited the synchronous regulation of target cells, of which regulatory performance has been verified by the upregulated levels of downstream genes/proteins and the increased cellular apoptosis. Our study demonstrated that the DNA tetrahedral nanomachine is a promising biosense-and-treat tool for the synchronous detection and regulation of intracellular miRNA, and is expected to be applied in the early diagnosis and tailored management of cancers.
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http://dx.doi.org/10.1016/j.mtbio.2022.100276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194454PMC
June 2022

ChIP-Hub provides an integrative platform for exploring plant regulome.

Nat Commun 2022 Jun 14;13(1):3413. Epub 2022 Jun 14.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.

Plant genomes encode a complex and evolutionary diverse regulatory grammar that forms the basis for most life on earth. A wealth of regulome and epigenome data have been generated in various plant species, but no common, standardized resource is available so far for biologists. Here, we present ChIP-Hub, an integrative web-based platform in the ENCODE standards that bundles >10,000 publicly available datasets reanalyzed from >40 plant species, allowing visualization and meta-analysis. We manually curate the datasets through assessing ~540 original publications and comprehensively evaluate their data quality. As a proof of concept, we extensively survey the co-association of different regulators and construct a hierarchical regulatory network under a broad developmental context. Furthermore, we show how our annotation allows to investigate the dynamic activity of tissue-specific regulatory elements (promoters and enhancers) and their underlying sequence grammar. Finally, we analyze the function and conservation of tissue-specific promoters, enhancers and chromatin states using comparative genomics approaches. Taken together, the ChIP-Hub platform and the analysis results provide rich resources for deep exploration of plant ENCODE. ChIP-Hub is available at https://biobigdata.nju.edu.cn/ChIPHub/ .
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http://dx.doi.org/10.1038/s41467-022-30770-1DOI Listing
June 2022

sp. nov. Isolated from Wound Infection After Pacemaker Implantation: Case Report and Literature Review.

Infect Drug Resist 2022 7;15:2915-2920. Epub 2022 Jun 7.

Department of Clinical Laboratory, Southwest Hospital, Army Medical University, Chongqing, People's Republic of China.

is a recognized pathogen in patients with immunodeficiency and a normal immune response, which can cause bacteremia, endocarditis, peritonitis and pulmonary infection. We report a case of wound infection after pacemaker implantation caused by . Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) was routinely used to identify the pathogen, and the results showed that the pathogen could not be accurately identified in the MALDI-TOF database at present. The 16S rRNA gene of the pathogen was further sequenced, and the result was . To the best of our knowledge, this is the first reported case of human infection caused by .
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http://dx.doi.org/10.2147/IDR.S368903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188390PMC
June 2022

Anti-IgLON5 antibodies cause progressive behavioral and neuropathological changes in mice.

J Neuroinflammation 2022 Jun 11;19(1):140. Epub 2022 Jun 11.

Department of Neurology & Institute of Neurology, Ruijin Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Background: Anti-IgLON5 disease is a rare neurological disorder associated with autoantibodies against the neuronal cell adhesion protein, IgLON5. Cellular investigations with human IgLON5 antibodies have suggested an antibody-mediated pathogenesis, but whether human IgLON5 autoantibodies can induce disease symptoms in mice is yet to be shown. Moreover, the effects of anti-IgLON5 autoantibodies on neurons and the precise molecular mechanisms in vivo remain controversial.

Methods: We investigated the effects of anti-IgLON5 antibodies in vivo and evaluated their long-term effects. We used two independent passive-transfer animal models and evaluated the effects of the antibodies on mouse behaviors at different time points from day 1 until day 30 after IgG infusion. A wide range of behaviors, including tests of locomotion, coordination, memory, anxiety, depression and social interactions were established. At termination, brain tissue was analyzed for human IgG, neuronal markers, glial markers, synaptic markers and RNA sequencing.

Results: These experiments showed that patient's anti-IgLON5 antibodies induced progressive and irreversible behavioral deficits in vivo. Notably, cognitive abnormality was supported by impaired average gamma power in the CA1 during novel object recognition testing. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies in the hippocampus of anti-IgLON5 IgG-injected mice, which persisted 30 days after the injection of patient's antibodies was stopped. Microglial and astrocyte density was increased in the hippocampus of anti-IgLON5 IgG-injected mice at Day 30. Whole-cell voltage clamp recordings proved that anti-IgLON5 antibodies affected synaptic homeostasis. Further western blot investigation of synaptic proteins revealed a reduction of presynaptic (synaptophysin) and post-synaptic (PSD95 and NMDAR1) expression in anti-IgLON5 IgG-injected mice.

Conclusions: Overall, our findings indicated an irreversible effect of anti-IgLON5 antibodies and supported the pathogenicity of these antibodies in vivo.
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http://dx.doi.org/10.1186/s12974-022-02520-zDOI Listing
June 2022

Temperature-Compensated Multi-Point Strain Sensing Based on Cascaded FBG and Optical FMCW Interferometry.

Sensors (Basel) 2022 May 24;22(11). Epub 2022 May 24.

State Key Laboratory of Optical Fiber and Cable Manufacture Technology, Yangtze Optical Fiber and Cable Joint Stock Limited Company, Wuhan 430073, China.

We proposed a novel temperature-compensated multi-point strain sensing system based on cascaded FBG and optical FMCW interferometry. The former is used for simultaneous sensing of temperature and strain, and the latter is used for position information reading and multiplexing. In the experiment, a narrow linewidth laser with continuous frequency-sweeping was used as the light source. After demodulating the beat-frequency signal, the link information of the 16 m fiber was obtained, and the measured result was identical to the actual position. The measurement accuracy reached 50.15 mm, and the dynamic range was up to 22.68 dB. Meanwhile, we completed the sensing experiments for temperature range from 20 °C to 90 °C and strain range from 0 με to 7000 με. The sensitivity of the sensing system to temperature was 10.21 pm/°C, the sensitivity and accuracy to strain were as high as 1.163 pm/με and 10 με, respectively. Finally, the measured strain and temperature values were obtained using the sensing matrix. The sensing system has important practical significance in the field of quasi-distributed strain measurement.
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http://dx.doi.org/10.3390/s22113970DOI Listing
May 2022

Reassessment of Reliability and Reproducibility for Triple-Negative Breast Cancer Subtyping.

Cancers (Basel) 2022 May 24;14(11). Epub 2022 May 24.

Department of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.

Triple-negative breast cancer (TNBC) is a heterogeneous disease with diverse, often poor prognoses and treatment responses. In order to identify targetable biomarkers and guide personalized care, scientists have developed multiple molecular classification systems for TNBC based on transcriptomic profiling. However, there is no consensus on the molecular subtypes of TNBC, likely due to discrepancies in technical and computational methods used by different research groups. Here, we reassessed the major steps for TNBC subtyping, validated the reproducibility of established TNBC subtypes, and identified two more subtypes with a larger sample size. By comparing results from different workflows, we demonstrated the limitations of formalin-fixed, paraffin-embedded samples, as well as batch effect removal across microarray platforms. We also refined the usage of computational tools for TNBC subtyping. Furthermore, we integrated high-quality multi-institutional TNBC datasets (discovery set: = 457; validation set: = 165). Performing unsupervised clustering on the discovery and validation sets independently, we validated four previously discovered subtypes: luminal androgen receptor, mesenchymal, immunomodulatory, and basal-like immunosuppressed. Additionally, we identified two potential intermediate states of TNBC tumors based on their resemblance with more than one well-characterized subtype. In summary, we addressed the issues and limitations of previous TNBC subtyping through comprehensive analyses. Our results promote the rational design of future subtyping studies and provide new insights into TNBC patient stratification.
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http://dx.doi.org/10.3390/cancers14112571DOI Listing
May 2022

Recombinant human erythropoietin upregulates PPARγ through the PI3K/Akt pathway to protect neurons in rats subjected to oxidative stress.

Eur J Neurosci 2022 Jun 9. Epub 2022 Jun 9.

Department of Neurology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

In vitro cell experiments have suggested that recombinant human erythropoietin (rhEPO) and peroxisome proliferator activated receptor γ (PPARγ) activation exert protective effects on neurons. This study observed the learning and memory ability, antioxidant capacity and the ratio of apoptotic cells after rhEPO intervention and investigated the relationship among rhEPO, PI3K/Akt and PPARγ in the anti-neural oxidative stress injury process in vivo. The results showed that rhEPO significantly improved the learning and memory abilities of rats subjected to oxidative stress, enhanced the antioxidant capacity of cells, and reduced neuronal apoptosis. Then, the PI3K/Akt and PPARγ pathways were inhibited, and TUNEL staining were used to observe the changes in the effect of rhEPO. After the PI3K/Akt and PPARγ pathways were inhibited, the effect of rhEPO on rats subjected to oxidative stress was significantly weakened, suggesting that both the PI3K/Akt and PPARγ pathways are involved in the process by which rhEPO protects neurons. Finally, Western blotting and immunofluorescence staining were used to observe the changes in PI3K/Akt and PPARγ signalling proteins in the neurons after the rhEPO intervention and to explore the relationship among the three. The results showed that rhEPO significantly increased the levels of the p-Akt and PPARγ proteins and the level of the PPARγ protein in the nucleus, indicating that the PI3K/Akt pathway was located upstream of and regulates PPARγ. In conclusion, this study suggested that rhEPO activates the PI3K/Akt to upregulate PPARγ, enhance the cellular antioxidant capacity, and protect neurons in rats subjected to oxidative stress.
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http://dx.doi.org/10.1111/ejn.15735DOI Listing
June 2022

Clinical Characteristics and Immune Status of Patients with Severe Fever with Thrombocytopenia Syndrome.

Viral Immunol 2022 Jun 8. Epub 2022 Jun 8.

Department of Intensive Care, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.

Severe fever with thrombocytopenia syndrome (SFTS) is a novel infectious disease caused by bunya virus. The purpose of this study was to investigate the clinical characteristics of SFTS patients and their virus-related immune disorders . Patients with SFTS admitted to Nanjing Drum Tower Hospital from 2017 to 2020 were retrospectively analyzed, and divided into survival group and death group according to the 28-day survival. Clinical characteristics and laboratory examination results of SFTS patients were recorded, and dynamic changes of immune function and inflammatory factors were statistically analyzed. Prolonged activated prothrombin time (APTT) ( = 0.001), high viral load ( = 0.001), and elevated human leukocyte antigen DR (HLA-DR) level ( = 0.002) were independent prognostic risk factors for SFTS patients. Compared to the survival group, the nonsurvival group was more prone to hemorrhagic and neurological symptoms ( < 0.05). Natural kill (NK) cell count, interleukin-10, interferon-, and tumor necrosis factor- scores in the nonsurvival group continued to increase after admission, while CD3 T, CD4 T, and CD8 T cell counts continued to decrease. CD3 T lymphocyte count was negatively correlated with viral load ( = 0.3883,  < 0.001), CD4 T lymphocyte count was negatively correlated with viral load ( = 0.28933,  < 0.001), CD8 T lymphocyte count was negatively correlated with viral load ( = 0.781,  < 0.001), and HLA-DR was positively correlated with viral load ( = 0.489,  < 0.001). High viral load, prolonged APTT time, and elevated HLA-DR level are independent prognostic risk factors for SFTS patients. The T lymphocyte subsets of SFTS patients continue to decrease after infection, and the number of T lymphocyte subsets can reflect the severity of the disease.
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http://dx.doi.org/10.1089/vim.2021.0217DOI Listing
June 2022

FuZhengHuaYuJiangZhuTongLuoFang Prescription Modulates Gut Microbiota and Gut-Derived Metabolites in UUO Rats.

Front Cell Infect Microbiol 2022 20;12:837205. Epub 2022 May 20.

Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Background: Alteration of intestinal flora and metabolites is closely related to chronic kidney disease (CKD) across early to advanced stages. FuZhengHuaYuJiangZhuTongLuoFang prescription (FZHY) is a Chinese herb that has been proven to effectively treat CKD, but the underlying mechanism is not clear.

Methods: Rats were subjected to intragastric treatment with FZHY 7, 14, and 21 days after unilateral ureteral obstruction (UUO) surgery, and kidney tissue, colon tissue, serum, and stool samples were collected.

Results: FZHY treatment effectively ameliorated UUO-induced renal function loss, renal injury and renal fibrosis, and colon tissue damage and fibrosis on day 7. The results of 16S flora analysis (day 7) showed that, compared with the UUO group, both the FZHY group and the sham group showed decreased levels of , , , and . Additionally, FZHY obviously induced the reduction of serum citrulline, glycoursodeoxycholic acid, 23-nordeoxycholic acid, 7-ketodeoxycholic acid, kahweol, lipoid B4, 4-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-2-methyl-1,3-thiazole, taurolithocholic acid sodium salt, indoline-2-carboxylic acid, 5(S),15(S)-diHETE, and others and the increase of bilirubin, asparagine, and others, which were positively associated with the above four candidate bacteria. Moreover, FZHY increased the levels of ZO-1, occludin, and claudin-1 in the colonic mucosa and reduced the levels of CRP, TNF-α, IL-6, and IL-1 in the serum and LN, FN, Col-I, and Col-III in the tubulointerstitium of UUO rats on day 7.

Conclusion: Our study revealed that FZHY reduced kidney damage at the early stage of CKD by regulating the above four candidate bacteria biomarkers and gut-derived harmful metabolites, inhibiting the inflammation response and tubulointerstitial fibrosis, providing deep insight into CKD therapeutic strategy.
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http://dx.doi.org/10.3389/fcimb.2022.837205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165620PMC
May 2022

Biomarker-based risk model to predict cardiovascular events in patients with acute coronary syndromes - Results from BIPass registry.

Lancet Reg Health West Pac 2022 Aug 30;25:100479. Epub 2022 May 30.

Department of Emergency and Chest Pain Center, Qilu Hospital, Shandong University, Jinan 250012, China.

Background: Risk models integrating new biomarkers to predict cardiovascular events in acute coronary syndromes (ACS) are lacking. Therefore, we evaluated the prognostic value of biomarkers in addition to clinical predictors and developed a biomarker-based risk model for major adverse cardiovascular events (MACE) within 12 months after hospital admission with ACS.

Methods: Patients ( = 4407) consecutively enrolled from November, 2017 to October, 2019 in three hospitals of a prospective Chinese registry (BIomarker-based Prognostic Assessment for Patients with Stable Angina and Acute Coronary Syndromes, BIPass) were designated as the risk model development cohort. Validation was performed in 1409 patients enrolled in two independent hospitals. Cox proportional hazards regression analysis was used to generate a risk prediction model and evaluate the incremental prognostic value of each biomarker.

Findings: Over 12 months, 196 patients experienced MACE (5.1%/year). Among twelve candidate biomarkers, N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured at baseline showed the most prognostic capability independent of clinical predictors. The developed BIPass risk model included age, hypertension, previous myocardial infarction, stroke, Killip class, heart rate, and NT-proBNP. It displayed improved discrimination (C-statistic 0.79, 95% CI 0.73-0.85), calibration (GOF = 9.82,  = 0.28) and clinical decision curve in the validation cohort, outperforming the GRACE and TIMI risk scores. Cumulative rates for MACE demonstrated good separation in the BIPass predicted low, intermediate, and high-risk groups.

Interpretation: The BIPass risk model, integrating clinical variables and NT-proBNP, is useful for predicting 12-month MACE in ACS. It effectively identifies a gradient risk of cardiovascular events to aid personalized care.

Funding: National Key R&D Program of China (2017YFC0908700, 2020YFC0846600), National S&T Fundamental Resources Investigation Project (2018FY100600, 2018FY100602), Taishan Pandeng Scholar Program of Shandong Province (tspd20181220), Taishan Young Scholar Program of Shandong Province (tsqn20161065, tsqn201812129), Youth Top-Talent Project of National Ten Thousand Talents Plan and Qilu Young Scholar Program.
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http://dx.doi.org/10.1016/j.lanwpc.2022.100479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160492PMC
August 2022
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