Publications by authors named "Jie Jiang"

792 Publications

Efficacy and Safety of Platinum-Based Chemotherapy as First-Line Therapy for Metastatic Triple-Negative Breast Cancer: A Meta-Analysis of Randomized Controlled Trials.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211016369

Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, 531840Tumor Hospital of Yunnan Province, Kunming, Yunnan, China.

Background: Triple-negative breast cancer constitutes approximately 12%-17% of all breast cancer cases, and >33% of patients develop distant metastases. Systemic cytotoxic chemotherapy is the primary treatment for patients with metastatic triple-negative breast cancer; however, the role of first-line platinum-based chemotherapy in these patients remains controversial. This meta-analysis evaluated the efficacy and safety of platinum-based first-line chemotherapy for patients with metastatic triple-negative breast cancer.

Methods: We systematically searched the PubMed, Embase, Cochrane, and Clinical Trials registry databases up to June 1, 2020 to identify randomized controlled trials that investigated platinum-based vs. first-line platinum-free chemotherapy in patients with metastatic triple-negative breast cancer. We used fixed and random effects models to calculate pooled hazard ratios and odds ratios with 95% confidence intervals for progression-free and overall survival, objective response rates, and grade 3 and 4 adverse events.

Results: Four randomized controlled trials ( = 590 patients) were included. Platinum-based chemotherapy significantly increased the objective response rates from 43.1% to 62.7% (odds ratio 2.34, 95% confidence interval 1.66-3.28, < 0.001). Three randomized controlled trials ( = 414 patients) reported survival outcomes. Patients administered platinum-based regimens showed significantly longer progression-free survival (hazard ratio 0.55, 95% confidence interval 0.37-0.82, = 0.004) and a nonsignificant trend toward improved overall survival (hazard ratio 0.76, 95% confidence interval 0.57-1.00, = 0.05). Only 2 studies reported the rates of grade 3 and 4 adverse events; grade 3-4 thrombocytopenia was more commonly associated with platinum-based chemotherapy (odds ratio 7.54, 95% confidence interval 1.37-41.60, = 0.02) and grade 3-4 fatigue with platinum-free chemotherapy (odds ratio 0.23, 95% confidence interval 0.08-0.68, = 0.008).

Conclusions: First-line platinum-based chemotherapy was associated with significantly increased objective response rates, longer progression-free survival, and a nonsignificant trend toward improved overall survival in patients with metastatic triple-negative breast cancer at the high risk of grade 3-4 thrombocytopenia.
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http://dx.doi.org/10.1177/15330338211016369DOI Listing
May 2021

Optimal margins for early stage peripheral lung adenocarcinoma resection.

BMC Cancer 2021 May 11;21(1):533. Epub 2021 May 11.

Wuxi Lung Transplant Center, Wuxi People's Hospital Affiliated to Nanjing Medical University, 299 QingYang Road, Wuxi, 214023, China.

Background: A pathologically confirmed negative margin is required when performing sublobar resection in patients with early stage peripheral lung adenocarcinoma. However, the optimal margin distance to ensure complete tumor resection while preserving healthy lung tissue remains unknown. We aimed to establish a reliable distance range for negative margins.

Methods: A total of 52 intraoperative para-cancer tissue specimens from patients with peripheral lung adenocarcinoma with pathological tumors ≤2 cm in size were examined. Depending on the distance from the tumor edge (D), the para-cancer tissues were divided into the following five groups: D < 0.5 cm (group I); 0.5 cm ≤ D < 1.0 cm (group II); 1.0 cm ≤ D < 1.5 cm (group III); 1.5 cm ≤ D < 2.0 cm (group IV); and D ≥ 2.0 cm (group V). During pathological examination of the specimens under a microscope, the presence of atypical adenomatous hyperplasia or more severe lesions was considered unsafe, whereas the presence of normal lung tissue or benign hyperplasia was considered safe.

Results: Group V, in which the margin was the farthest from the tumor edge, was the safest. There were significant safety differences in between groups I and V (χ = 26.217, P < 0.001). Significant safety differences also existed between groups II and V (χ = 9.420, P < 0.005). There were no significant safety differences between group III or IV and group V (P = 0.207; P = 0.610).

Conclusions: We suggest that when performing sublobar resection in patients with early stage peripheral lung adenocarcinoma with pathological tumor sizes ≤2 cm, the resection margin distance should be ≥1 cm to ensure a negative margin.
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http://dx.doi.org/10.1186/s12885-021-08251-3DOI Listing
May 2021

TRIM68, PIKFYVE, and DYNLL2: The Possible Novel Autophagy- and Immunity-Associated Gene Biomarkers for Osteosarcoma Prognosis.

Front Oncol 2021 22;11:643104. Epub 2021 Apr 22.

Department of Spinal Orthopedics, The First Clinical Affiliated Hospital of Guangxi Medical University, Nanning, China.

Introduction: Osteosarcoma is among the most common orthopedic neoplasms, and currently, there are no adequate biomarkers to predict its prognosis. Therefore, the present study was aimed to identify the prognostic biomarkers for autophagy-and immune-related osteosarcoma using bioinformatics tools for guiding the clinical diagnosis and treatment of this disease.

Materials And Methods: The gene expression and clinical information data were downloaded from the Public database. The genes associated with autophagy were extracted, followed by the development of a logistic regression model for predicting the prognosis of osteosarcoma using univariate and multivariate COX regression analysis and LASSO regression analysis. The accuracy of the constructed model was verified through the ROC curves, calibration plots, and Nomogram plots. Next, immune cell typing was performed using CIBERSORT to analyze the expression of the immune cells in each sample. For the results obtained from the analysis, we used qRT-PCR validation in two strains of human osteosarcoma cells.

Results: The screening process identified a total of three genes that fulfilled all the screening criteria. The survival curves of the constructed prognostic model revealed that patients with the high risk presented significantly lower survival than the patients with low risk. Finally, the immune cell component analysis revealed that all three genes were significantly associated with the immune cells. The expressions of TRIM68, PIKFYVE, and DYNLL2 were higher in the osteosarcoma cells compared to the control cells. Finally, we used human pathological tissue sections to validate the expression of the genes modeled in osteosarcoma and paracancerous tissue.

Conclusion: The TRIM68, PIKFYVE, and DYNLL2 genes can be used as biomarkers for predicting the prognosis of osteosarcoma.
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http://dx.doi.org/10.3389/fonc.2021.643104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101494PMC
April 2021

Structure-activity relationship study of THZ531 derivatives enables the discovery of BSJ-01-175 as a dual CDK12/13 covalent inhibitor with efficacy in Ewing sarcoma.

Eur J Med Chem 2021 Apr 20;221:113481. Epub 2021 Apr 20.

Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA. Electronic address:

Development of inhibitors targeting CDK12/13 is of increasing interest as a potential therapy for cancers as these compounds inhibit transcription of DNA damage response (DDR) genes. We previously described THZ531, a covalent inhibitor with selectivity for CDK12/13. In order to elucidate structure-activity relationship (SAR), we have undertaken a medicinal chemistry campaign and established a focused library of THZ531 analogs. Among these analogs, BSJ-01-175 demonstrates exquisite selectivity, potent inhibition of RNA polymerase II phosphorylation, and downregulation of CDK12-targeted genes in cancer cells. A 3.0 Å co-crystal structure with CDK12/CycK provides a structural rational for selective targeting of Cys1039 located in a C-terminal extension from the kinase domain. With moderate pharmacokinetic properties, BSJ-01-175 exhibits efficacy against an Ewing sarcoma tumor growth in a patient-derived xenograft (PDX) mouse model following 10 mg/kg once a day, intraperitoneal administration. Taken together, BSJ-01-175 represents the first selective CDK12/13 covalent inhibitor with in vivo efficacy reported to date.
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http://dx.doi.org/10.1016/j.ejmech.2021.113481DOI Listing
April 2021

Convergence analysis of sample average approximation for a class of stochastic nonlinear complementarity problems: from two-stage to multistage.

Numer Algorithms 2021 Apr 27:1-28. Epub 2021 Apr 27.

Jiangsu Key Laboratory for NSLSCS, School of Mathematical Sciences, Nanjing Normal University, Nanjing, 210023 China.

In this paper, we consider the sample average approximation (SAA) approach for a class of stochastic nonlinear complementarity problems (SNCPs) and study the corresponding convergence properties. We first investigate the convergence of the SAA counterparts of two-stage SNCPs when the first-stage problem is continuously differentiable and the second-stage problem is locally Lipschitz continuous. After that, we extend the convergence results to a class of multistage SNCPs whose decision variable of each stage is influenced only by the decision variables of adjacent stages. Finally, some preliminary numerical tests are presented to illustrate the convergence results.
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http://dx.doi.org/10.1007/s11075-021-01110-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076443PMC
April 2021

Overexpression of Inhibits the Growth of Rice and Causes Spontaneous Cell Death.

Genes (Basel) 2021 Apr 27;12(5). Epub 2021 Apr 27.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China.

The Mediator complex transduces information from the DNA-bound transcription factors to the RNA polymerase II transcriptional machinery. Research on plant Mediator subunits has primarily been performed in Arabidopsis, while very few of them have been functionally characterized in rice. In this study, the rice Mediator subunit 16, was examined. encodes a putative protein of 1301 amino acids, which is longer than the version previously reported. It was expressed in various rice organs and localized to the nucleus. The knockout of resulted in rice seedling lethality. Its overexpression led to the retardation of rice growth, low yield, and spontaneous cell death in the leaf blade and sheath. RNA sequencing suggested that the overexpression of altered the expression of a large number of genes. Among them, the upregulation of some defense-related genes was verified. can regulate the expression of a wealth of genes, and alterations in its expression have a profound impact on plant growth, development, and defense responses in rice.
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http://dx.doi.org/10.3390/genes12050656DOI Listing
April 2021

Discovery of a Potent Degrader for Fibroblast Growth Factor Receptor 1/2.

Angew Chem Int Ed Engl 2021 Apr 29. Epub 2021 Apr 29.

Harvard Medical School, Dana Farber Cancer Institute, 360 Longwood Avenue, 2115, Boston, UNITED STATES.

Aberrant activation of FGFR signaling occurs in many cancers, and ATP-competitive FGFR inhibitors have received regulatory approval. Despite demonstrating clinical efficacy, these inhibitors exhibit dose-limiting toxicity, potentially due to a lack of selectivity amongst the FGFR family and are poorly tolerated. Here, we report the discovery and characterization of DGY-09-192, a bivalent degrader that couples the pan-FGFR inhibitor BGJ398 to a CRL2 VHL E3 ligase recruiting ligand, which preferentially induces FGFR1&2 degradation while largely sparing FGFR3&4. DGY-09-192 exhibited two -digit nanomolar DC 50 s for both wildtype FGFR2 and several FGFR2-fusions, resulting in degradation-dependent antiproliferative activity in representative gastric cancer and cholangiocarcinoma cells. Importantly, DGY-09-192 induced degradation of a clinically relevant FGFR2 fusion protein in a xenograft model. Taken together, we demonstrate that DGY-09-192 has potential as a prototype FGFR degrader.
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http://dx.doi.org/10.1002/anie.202101328DOI Listing
April 2021

Identification of Hub Genes Associated With Melanoma Development by Comprehensive Bioinformatics Analysis.

Front Oncol 2021 12;11:621430. Epub 2021 Apr 12.

Spinal Orthopedic Ward, The First Clinical Affiliated Hospital of Guangxi Medical University, Nanning, China.

Introduction: This study aimed to identify important genes associated with melanoma to further develop new target gene therapies and analyze their significance concerning prognosis.

Materials And Methods: Gene expression data for melanoma and normal tissue were downloaded from three databases. Differentially co-expressed genes were identified by WGCNA and DEGs analysis. These genes were subjected to GO, and KEGG enrichment analysis and construction of the PPI visualized with Cytoscape and screened for the top 10 Hub genes using CytoHubba. We validated the Hub gene's protein levels with an immunohistochemical assay to confirm the accuracy of our analysis.

Results: A total of 435 differentially co-expressed genes were obtained. Survival curves showed that high expression of FOXM1,\ EXO1, KIF20A, TPX2, and CDC20 in melanoma patients with 5 of the top 10 hub genes was associated with reduced overall survival (OS). Immunohistochemistry showed that all five genes were expressed at higher protein levels in melanoma than in paracancerous tissues.

Conclusion: FOXM1, EXO1, KIF20A, TPX2, and CDC20 are prognosis-associated core genes of melanoma, and their high expression correlates with the low prognosis of melanoma patients and can be used as biomarkers for melanoma diagnosis, treatment, and prognosis prediction.
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http://dx.doi.org/10.3389/fonc.2021.621430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072149PMC
April 2021

MYC-Protein Arginine Methyltransferase 5 Axis Defines the Tumorigenesis and Immune Response in Hepatocellular Carcinoma.

Hepatology 2021 Apr 25. Epub 2021 Apr 25.

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally with poor outcome and limited therapeutic options. Although the MYC oncogene is frequently dysregulated in HCC, it is thought to be undruggable. Thus, the current study aimed to identify the critical downstream metabolic network of MYC and develop new therapies for MYC-driven HCC. Liver cancer was induced in mice with hepatocyte-specific disruption of Myc and control mice by administration of diethylnitrosoamine (DEN). Liquid chromatography coupled with mass spectrometry-based metabolomic analyses revealed that urinary dimethylarginine, especially symmetric dimethylarginine (SDMA), was increased in the HCC mouse model in a MYC-dependent manner. Analyses of human samples demonstrated a similar induction of SDMA in the urines from HCC patients. Mechanistically, Prmt5, encoding protein arginine methyltransferase 5, which catalyzes SDMA formation from arginine, was highly induced in HCC and identified as a direct MYC target gene. Moreover, GSK3326595, a PRMT5 inhibitor, suppressed the growth of liver tumors in human MYC-overexpressing transgenic mice that spontaneously develop HCC. Inhibition of PRMT5 exhibited anti-proliferative activity via upregulation of the tumor suppressor gene Cdkn1b/p27. In addition, GSK3326595 induced lymphocyte infiltration and MHC II expression, which might contribute to the enhanced anti-tumor immune response. Combination of GSK3326595 with anti-PD-1 immune checkpoint therapy (ICT) improved therapeutic efficacy in HCC. This study revealed that PRMT5 is an epigenetic executer of MYC leading to repression of the transcriptional regulation of downstream genes that promote hepatocellular carcinogenesis, highlights a mechanism-based therapeutic strategy for MYC-driven HCC via PRMT5 inhibition through synergistically suppressed proliferation and enhanced anti-tumor immunity, and finally provides an opportunity to mitigate the resistance of "immune-cold" tumor to ICT.
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http://dx.doi.org/10.1002/hep.31864DOI Listing
April 2021

Cost-effectiveness analysis of ribociclib plus fulvestrant for hormone receptor-positive/human EGF receptor 2-negative breast cancer.

Immunotherapy 2021 Jun 20;13(8):661-668. Epub 2021 Apr 20.

College of Pharmacy, Jinan University, Guangzhou 510632, China.

To evaluate the cost-effectiveness of ribociclib plus fulvestrant versus fulvestrant in hormone receptor-positive/human EGF receptor 2-negative advanced breast cancer. A three-state Markov model was developed to evaluate the costs and effectiveness over 10 years. Direct costs and utility values were obtained from previously published studies. We calculated incremental cost-effectiveness ratio to evaluate the cost-effectiveness at a willingness-to-pay threshold of $150,000 per additional quality-adjusted life year. The incremental cost-effectiveness ratio was $1,073,526 per quality-adjusted life year of ribociclib plus fulvestrant versus fulvestrant. Ribociclib plus fulvestrant is not cost-effective versus fulvestrant in the treatment of advanced hormone receptor-positive/human EGF receptor 2-negative breast cancer. When ribociclib is at 10% of the full price, ribociclib plus fulvestrant could be cost-effective.
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http://dx.doi.org/10.2217/imt-2020-0237DOI Listing
June 2021

HBx induces hepatocellular carcinogenesis through ARRB1-mediated autophagy to drive the G/S cycle.

Autophagy 2021 Apr 27:1-19. Epub 2021 Apr 27.

Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China.

The hepatitis B virus X protein (HBx) is involved in the process of hepatocellular carcinoma via the activation of various oncogenes. Our previous study indicated that ARBB1 (arrestin beta 1) promotes hepatocellular carcinogenesis (HCC). However, the role of ARRB1 in HBx-related HCC remains unclear. Herein, we identified that ARRB1 was upregulated by HBx and deficiency suppressed HBx-induced hepatocellular carcinogenesis in several mouse models. Furthermore, knockdown of blocked HBx-induced macroautophagic/autophagic flux and disrupted the formation of autophagosomes. ARRB1 interacted with HBx, and the autophagic core protein MAP1LC3/LC3, a scaffolding protein, was essential for complete autophagy. Inhibition of autophagy by 3-methyladenine or interference of or attenuated HBx-induced cell cycle acceleration and the subsequent proliferative response via the induction of G/S arrest. The absence of autophagy abolished the phosphorylation of CDK2 and the activity of the CDK2-CCNE1 complex. Our results demonstrate that ARRB1 plays a critical role in HBV-related HCC via modulating autophagy and the CDKN1B-CDK2-CCNE1-E2F1 axis and indicate that ARRB1 may be a potential therapeutic target for HCC.
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http://dx.doi.org/10.1080/15548627.2021.1917948DOI Listing
April 2021

Bacterial and Microfauna Mechanisms for Sludge Reduction in Carrier-Enhanced Anaerobic Side-Stream Reactors Revealed by Metagenomic Sequencing Analysis.

Environ Sci Technol 2021 05 15;55(9):6257-6269. Epub 2021 Apr 15.

Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China.

Packing carriers into the anaerobic side-stream reactor (ASSR) can enhance sludge reduction and save footprint by investigating ASSR-coupled membrane bioreactors (AP-MBRs) under different hydraulic residence times of the ASSR (HRT). Three AP-MBRs and an anoxic-aerobic MBR (AO-MBR) showed efficient chemical oxygen demand (>94.2%) and ammonium nitrogen removal (>99.3%). AP-MBRs have higher ( < 0.05) total nitrogen (61.4-67.7%) and total phosphorus (57.5-63.8%) removal than AO-MBRs (47.8 and 47.7%). AP-MBRs achieved sludge reduction efficiencies of 11.8, 31.8, and 36.2% at HRT values of 2.5, 5.0, and 6.7 h. Packing carriers greatly improved sludge reduction under low HRT and is promising for accelerating sludge reduction in compact space. Metagenomic sequencing analysis showed that genes responsible for metabolism were enriched in AO-MBRs, while genes related to cellular motility and cell signaling were more abundant in the AP-MBRs. A longevity-regulating pathway showed that long lifespan provided more opportunities for worms to prey bacteria. Microscopic examination revealed that some specific protozoa (, , , , and ) and metazoa ( and ) were enriched in ASSRs. was only detected in ASSRs, and unique appeared on carriers. These results contribute to growing understanding of micrometabolic mechanisms including functional genes and microfauna-driving sludge reduction.
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http://dx.doi.org/10.1021/acs.est.0c07880DOI Listing
May 2021

The Role of Oxidative Stress in Hyperuricemia and Xanthine Oxidoreductase (XOR) Inhibitors.

Oxid Med Cell Longev 2021 26;2021:1470380. Epub 2021 Mar 26.

Basic Medical College, Anhui Medical University, Hefei 230032, China.

Uric acid is the end product of purine metabolism in humans. Hyperuricemia is a metabolic disease caused by the increased formation or reduced excretion of serum uric acid (SUA). Alterations in SUA homeostasis have been linked to a number of diseases, and hyperuricemia is the major etiologic factor of gout and has been correlated with metabolic syndrome, cardiovascular disease, diabetes, hypertension, and renal disease. Oxidative stress is usually defined as an imbalance between free radicals and antioxidants in our body and is considered to be one of the main causes of cell damage and the development of disease. Studies have demonstrated that hyperuricemia is closely related to the generation of reactive oxygen species (ROS). In the human body, xanthine oxidoreductase (XOR) catalyzes the oxidative hydroxylation of hypoxanthine to xanthine to uric acid, with the accompanying production of ROS. Therefore, XOR is considered a drug target for the treatment of hyperuricemia and gout. In this review, we discuss the mechanisms of uric acid transport and the development of hyperuricemia, emphasizing the role of oxidative stress in the occurrence and development of hyperuricemia. We also summarize recent advances and new discoveries in XOR inhibitors.
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http://dx.doi.org/10.1155/2021/1470380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019370PMC
March 2021

Comfortable suture angle with optimized trocar position aids renorrhaphy during retroperitoneal laparoscopic partial nephrectomy.

Transl Androl Urol 2021 Mar;10(3):1030-1039

Department of Urology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

Background: This study investigated a comfortable suture angle (CSA) with optimized trocar position for closing the defect during renorrhaphy in retroperitoneal laparoscopic partial nephrectomy (LPN). The feasibility, usefulness, and safety of achieving the CSA with modified trocar position were determined for different tumor types.

Methods: Two optimized trocar positions were introduced for different tumor types. A suture angle was based on the tumor plane of the superficial parenchyma defect and the line formed by the needle holder. Preliminary surgical simulations determined a CSA that combined the least suture time with the greatest ease of performance. Achieving the CSA was attempted during renorrhaphy of 106 enrolled patients undergoing retroperitoneal LPN. Patients' characteristics, operative features, and follow-up information were collected and analyzed.

Results: For 89 (83.96%) patients, a CSA was successfully reached and parenchyma recovered. The remaining 17 patients were successfully sutured, but the attempt to achieve a CSA failed. For the CSA group, the suture, clamping, and overall operative times were significantly less than that of the non-CSA patients. The groups were similar regarding estimated blood loss, positive surgical margin, and rates of glomerular filtration reduction and complications. Univariable analyses determined that tumor location, growth pattern, and R.E.N.A.L. nephrometry score (RNS) may influence the success of this approach. Multivariable analyses indicated that only tumor location and RNS were independent factors affecting successful achievement of the CSA.

Conclusions: Through different kidney position changes, the CSA could be used to ease the suture process. It is feasible and safe to perform a CSA with optimized trocar position during LPN. Tumor location and RNS may influence the approach to get a CSA.
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http://dx.doi.org/10.21037/tau-20-1126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039601PMC
March 2021

Structural and kinetic characterization of glutaminyl cyclase.

Biol Chem 2021 Apr 7. Epub 2021 Apr 7.

Department of Biological Sciences, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou, Jiangsu215123, China.

is a bacterial species known to be involved in the pathogenesis of chronic periodontitis, that more recently has been as well associated with Alzheimer's disease. expresses a glutaminyl cyclase (PgQC) whose human ortholog is known to participate in the beta amyloid peptide metabolism. We have elucidated the crystal structure of PgQC at 1.95 Å resolution in unbound and in inhibitor-complexed forms. The structural characterization of PgQC confirmed that PgQC displays a mammalian fold rather than a bacterial fold. Our biochemical characterization indicates that PgQC uses a mammalian-like catalytic mechanism enabled by the residues Asp, Glu, Asp, Asp, Asp and His. In addition, we could observe that a non-conserved Trp may drive differences in the binding affinity of ligands which might be useful for drug development. With a screening of a small molecule library, we have identified a benzimidazole derivative rendering PgQC inhibition in the low micromolar range that might be amenable for further medicinal chemistry development.
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http://dx.doi.org/10.1515/hsz-2020-0298DOI Listing
April 2021

Comparing the measurement properties of the EQ-5D-5L and the EQ-5D-3L in hypertensive patients living in rural China.

Qual Life Res 2021 Apr 5. Epub 2021 Apr 5.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

Purpose: The purpose of this study was to compare the measurement properties of two versions of EQ-5D (i.e.EQ-5D-3L and EQ-5D-5L) in hypertensive patients in rural China.

Methods: A cross-sectional survey was carried out in hypertensive patients in rural China. We compared the ceiling effects, redistribution properties, informativity, known-groups validity, and relative efficiency of the 3L and 5L and examined their agreement.

Results: A total of 11,412 patients were enrolled in our study. The mean EQ-5D index score was 0.84 (SD 0.21) according to the 5L and 0.86 (SD 0.17) according to the 3L. A good agreement was observed between the 3L and 5L. The overall ceiling effect decreased from 46.4% (3L) to 29.4% (5L). The Shannon index, H' improved in all dimensions when used 5L. When used 3L, the median responses of all groups were consistent with 5L across the three dimensions of 'mobility', 'self-care', 'usual activities', while the median responses were inconsistent for the 'pain/discomfort' and 'anxiety/depression' dimensions. The 3L performed better in eight comorbidities in terms of F-statistics and six comorbidities in terms of the area under the receiver operating characteristic curves (AUROCs). The 5L performed better both in terms of the F-statistics and AUROCs in age, education level, anti-hypertensive medication use.

Conclusion: Taking all comparisons into account, we recommend the EQ-5D-5L for use in patients with hypertension in rural China.
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http://dx.doi.org/10.1007/s11136-021-02786-5DOI Listing
April 2021

Protective effects of gastrodin pretreatment on mouse hepatic ischemia-reperfusion occurring through antioxidant and anti-apoptotic mechanisms.

Exp Ther Med 2021 May 8;21(5):471. Epub 2021 Mar 8.

Department of Gastroenterology and Hepatology, Institute of Digestive Disease, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China.

Hepatic ischemia-reperfusion injury (HIRI) often occurs following surgical procedures such as liver resection and transplantation. However, despite its clinical prominence, to the best of our knowledge, there remain no effective strategies to treat HIRI. Therefore, the aim of present study was to identify therapeutic agents that can exert beneficial effects against HIRI. The present study found that following hepatic IR modeling in mice, gastrodin (Gas) pretreatment improved the IR outcomes in terms of the serum biochemical indexes (alanine transaminase and aspartate transaminase), tissue biochemical indexes (superoxide dismutase, malondialdehyde and reduced glutathione content) and tissue pathology (H&E staining). In addition, compared with those in the IR + vehicle group, the IR + Gas group showed upregulated expression levels of nuclear erythroid 2-related factor 2, heme oxygenase 1 and Bcl-2 as detected by western blotting and reverse transcription-quantitative PCR. The mRNA and protein expression levels of Bax and caspase-3 were downregulated in the IR + Gas group compared with the IR + vehicle group. Concurrently, no significant differences were observed in the parameters between the Sham + vehicle and the Sham + Gas groups, indicating that Gas pretreatment may not cause liver damage. In conclusion, the findings of the present study revealed that Gas pretreatment exerted a protective effect in HIRI through both antioxidant and anti-apoptotic mechanisms.
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http://dx.doi.org/10.3892/etm.2021.9902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976389PMC
May 2021

Circulating PGLYRP1 Levels as a Potential Biomarker for Coronary Artery Disease and Heart Failure.

J Cardiovasc Pharmacol 2021 May;77(5):578-585

Department of Cardiology, Institute of Cardiovascular Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; and.

Abstract: Coronary artery disease (CAD) and associated comorbidities such as heart failure (HF) remain the leading cause of morbidity and mortality worldwide attributed to, at least partially, the lack of biomarkers for efficient disease diagnosis. Here, we evaluated the diagnostic potential of serum peptidoglycan recognition protein 1 (PGLYRP1), an important component of the innate immunity and inflammation system, for both CAD and HF. A machine-learning method (random forest) was used to evaluate the clinical utility of circulating PGLYRP1 for diagnosis of CAD and HF in a total of 370 individuals. Causal links of chronic serum PGLYRP1 elevation to both diseases were further explored in ApoE-/- mice. The serum levels of PGLYRP1 were significantly higher in individuals with either chronic CAD or acute coronary syndrome than those in those without coronary artery stenosis (the control group) and even more pronounced in CAD individuals with concomitant HF. Our random forest classifier revealed that this protein performed better than other recommended clinical indicators in distinguishing the CAD from the control individuals. In addition, this protein associates more with the biomarkers of HF including left ventricular ejection fraction than inflammation. Notably, our mice experiment indicated that long-term treatment with recombinant PGLYRP1 could significantly impair the cardiovascular system as reflected from both increased atherogenic lesions and reduced fractional shortening of the left ventricle. Our findings, therefore, supported the circulating levels of PGLYRP1 as a valuable biomarker for both CAD and HF.
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http://dx.doi.org/10.1097/FJC.0000000000000996DOI Listing
May 2021

Overexpression of Taspase 1 Predicts Poor Prognosis in Patients with Hepatocellular Carcinoma.

Cancer Manag Res 2021 16;13:2517-2537. Epub 2021 Mar 16.

Department of Gastroenterology and Hepatology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.

Background: Taspase 1 (TASP1) is a highly conserved protease involved in site-specific proteolysis. Existing researches have revealed a link between TASP1 expression and carcinogenesis. However, limited data are available regarding the prognosis and functions of TASP1 in hepatocellular carcinoma (HCC).

Methods: Western Blotting and qRT-PCR were employed to evaluate the level of TASP1 in HCC cell lines and clinical specimens. TASP1 expression was further calculated in clinical specimens by immunohistochemistry and the mRNA level of TASP1 in HCC was analyzed using Oncomine and UALCAN databases. The TASP1 promoter methylation modification was shown via MEXPRESS and UALCAN. The association between TASP1 expression and postoperative prognosis was evaluated using Kaplan-Meier and Cox regression analysis in clinical patients. The effect of TASP1 on HCC prognosis was analyzed via Kaplan-Meier plotter, GEPIA and UALCAN. Additionally, the regulators, kinases, miRNA and transcription factor targets of TASP1 were identified using LinkedOmics. Moreover, cBioPortal was used to detect the genetic alteration of TASP1. Finally, TIMER was utilized to assess the relation between TASP1 and the immune cell infiltration, whereas the correlation of TASP1 with three immune factors was detected through TISIDB.

Results: TASP1 expression was increased in HCC cell lines and HCC tissues. CNV and DNA methylation of TASP1 were changed. Survival analysis revealed that high TASP1 expression was correlated with overall survival (OS). Functional network analysis about TASP1 in HCC showed that the double-strand break repair, peptidyl-threonine modification, spindle organization, peptidyl-lysine modification and microtubule-based movement were modulated. Furthermore, TASP1 expression revealed puissant relation to the infiltration of immune cells and three immune factors in HCC.

Conclusion: These data indicate that TASP1 may act as a potential prognostic marker in HCC and regulate HCC via multiple mechanisms.
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http://dx.doi.org/10.2147/CMAR.S296069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981154PMC
March 2021

Discovery and resistance mechanism of a selective CDK12 degrader.

Nat Chem Biol 2021 Mar 22. Epub 2021 Mar 22.

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.

Cyclin-dependent kinase 12 (CDK12) is an emerging therapeutic target due to its role in regulating transcription of DNA-damage response (DDR) genes. However, development of selective small molecules targeting CDK12 has been challenging due to the high degree of homology between kinase domains of CDK12 and other transcriptional CDKs, most notably CDK13. In the present study, we report the rational design and characterization of a CDK12-specific degrader, BSJ-4-116. BSJ-4-116 selectively degraded CDK12 as assessed through quantitative proteomics. Selective degradation of CDK12 resulted in premature cleavage and poly(adenylation) of DDR genes. Moreover, BSJ-4-116 exhibited potent antiproliferative effects, alone and in combination with the poly(ADP-ribose) polymerase inhibitor olaparib, as well as when used as a single agent against cell lines resistant to covalent CDK12 inhibitors. Two point mutations in CDK12 were identified that confer resistance to BSJ-4-116, demonstrating a potential mechanism that tumor cells can use to evade bivalent degrader molecules.
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http://dx.doi.org/10.1038/s41589-021-00765-yDOI Listing
March 2021

LncRNA-ZXF1 regulates P21 expression in endometrioid endometrial carcinoma by managing ubiquitination-mediated degradation and miR-378a-3p/PCDHA3 axis.

Mol Oncol 2021 Mar 9. Epub 2021 Mar 9.

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China.

Long noncoding RNAs (lncRNAs) have a profound effect on biological processes in various malignancies. However, few studies have investigated their functions and specific mechanisms in endometrial cancer. In this study, we focused on the role and mechanism of lncRNA-ZXF1 in endometrial cancer. Bioinformatics and in viro and in vivo experiments were used to explore the expression and function of lncRNA-ZXF1. We identified lncRNA-ZXF1 altered the migration and invasion of endometrioid endometrial cancer (EEC) cells. Furthermore, our results suggest that lncRNA-ZXF1 regulates EEC cell proliferation. This regulation may be achieved by the lncRNA-ZXF1-mediated alteration in the expression of P21 through two mechanisms. One is that lncRNA-ZXF1 functions as a molecular sponge of miR-378a-3p to regulate PCDHA3 expression and then modulate the expression of P21. The other is that lncRNA-ZXF1 inhibits CDC20-mediated degradation of ubiquitination by directly binding to P21. To the best of our knowledge, this study is the first to explore lncRNA-ZXF1 functioning as a tumor-suppressing lncRNA in EEC. LncRNA-ZXF1 may become therapeutic, diagnostic, and prognostic indicator in the future.
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http://dx.doi.org/10.1002/1878-0261.12940DOI Listing
March 2021

The Membrane Interaction of Alpha-Synuclein.

Front Cell Neurosci 2021 4;15:633727. Epub 2021 Mar 4.

Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China.

A presynaptic protein closely related to Parkinson's disease (PD), α-synuclein (α-Syn), has been studied extensively regarding its pathogenic mechanisms. As a physiological protein in presynapses, however, α-Syn's physiological function remains unclear. Its location in nerve terminals and effects on membrane fusion also imply its functional role in synaptic transmission, including its possible interaction with high-curvature membranes its N-terminus and amorphous C-terminus. PD-related mutants that disrupt the membrane interaction (e.g., A30P and G51D) additionally suggest a relationship between α-Syn's pathogenic mechanisms and physiological roles through the membrane binding. Here, we summarize recent research on how α-Syn and its variants interact with membranes and influence synaptic transmission. We list several membrane-related connections between the protein's physiological function and the pathological mechanisms that stand to expand current understandings of α-Syn.
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http://dx.doi.org/10.3389/fncel.2021.633727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969880PMC
March 2021

Attenuated and delayed niacin skin flushing in schizophrenia and affective disorders: A potential clinical auxiliary diagnostic marker.

Schizophr Res 2021 Mar 4;230:53-60. Epub 2021 Mar 4.

Bio-X Institutes, Shanghai Mental Health Center, Shanghai Jiao Tong University, Shanghai, China; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychiatry Disorders, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Aim: Schizophrenia and affective disorders all show high heterogeneity in clinical manifestations. A lack of objective biomarkers has long been a challenge in the clinical diagnosis of these diseases. In this study, we aimed to investigate the performance of niacin skin flushing in schizophrenia and affective disorders and determine its clinical potential as an auxiliary diagnostic marker.

Methods: In this case-control study, niacin skin-flushing tests were conducted in 613 patients (including 307 schizophrenia patients, 179 bipolar disorder patients, and 127 unipolar depression patients) and 148 healthy controls (HCs) with a modified method. Differences in niacin skin-flushing responses were compared with adjustment for gender, BMI, age, nicotine dependence, alcohol consumption and educational status. A diagnostic model was established based on a bivariate cut-off.

Results: Schizophrenia and affective disorders showed similar performance of niacin bluntness, characterized by attenuated flushing extent and reduced flushing rate. An innovative bivariate cut-off was established according to these two features, by which we could identify -patients with either schizophrenia or affective disorders from HCs with a sensitivity of 55.28%, a specificity of 83.56% and a positive predictive value of 93.66%.

Conclusions: The niacin-induced skin flushing was prevalently blunted in patients with schizophrenia or affective disorders, indicating a promising potential as an auxiliary diagnostic marker in risk prediction and clinical management of these disorders. Additionally, the niacin-blunted subgroup implies a common biological basis in the investigated disorders, which provokes new thoughts in elucidating the pathological mechanisms.
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http://dx.doi.org/10.1016/j.schres.2021.02.009DOI Listing
March 2021

Responses of microbial structures, functions and metabolic pathways for nitrogen removal to different hydraulic retention times in anaerobic side-stream reactor coupled membrane bioreactors.

Bioresour Technol 2021 Jun 25;329:124903. Epub 2021 Feb 25.

Shanghai Engineering Research Center of Energy - Saving in Heat Exchange Systems, Shanghai University of Electric Power, Shanghai 200090, China.

Synchronous sludge reduction and nitrogen removal have attracted increasing attention, while the underlying mechanisms of diverse nitrogen metabolism within the complicated processes remain unclear. Four anoxic/oxic membrane bioreactors, three of which were upgraded by anaerobic side-stream reactors (ASSR) and carriers (APSSR-MBRs), were operated to determine effects of hydraulic retention time of ASSRs. APSSR-MBRs achieved more significant nitrogen removal and higher nitrate uptake rate because of more denitrifying bacteria and the supernumerary release of secondary substrates. Ammonia uptake rate showed the diverse Nitrospira preceded over anaerobic decay and sulfide inhibition in the ASSR, and made the reactor exhibit higher nitrification capacity. Metagenomic analysis indicated that APSSR-MBRs showed higher abundances of genes related to nitrogen consumption processes, and higher abundances on the carriers, confirming their pivotal roles in nitrogen metabolism. This study provided novel perspectives to build a bridge between process model and nitrogen metabolism in the sludge reduction system..
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http://dx.doi.org/10.1016/j.biortech.2021.124903DOI Listing
June 2021

Advances in the Treatment of Anal Fistula: A Mini-Review of Recent Five-Year Clinical Studies.

Front Surg 2020 11;7:586891. Epub 2021 Feb 11.

Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China.

Anal fistula, with its complicated pathogenesis, has been considered as a clinical challenge for centuries. The risk of frequent recurrence and incontinence constitutes a considerable threat in the long-term treatment of anal fistula. In this work, we narratively reviewed the scientific literature of new techniques that have been used for anal fistula treatment over the recent 5 years, objectively evaluated the pros and cons of each technique on the basis of clinical outcomes, and tried to disclose the effective strategies for anal fistula treatment. Up to date, surgery is the main method used for treating anal fistula, but there is no simple technique that can completely heal complex anal fistula. In the course of surgery treatment, the healing outcome, and the protection of anal function should be weighed comprehensively. Among the innovative techniques that have emerged in recent years, combined techniques based on drainage Seton and LIFT-plug seem to be the relatively effective therapies, but their effectiveness requires more multi-center prospective randomized controlled trials with large sample size and long-term follow-up to be validated.
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http://dx.doi.org/10.3389/fsurg.2020.586891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905164PMC
February 2021

Decreased serum apolipoprotein A4 as a potential peripheral biomarker for patients with schizophrenia.

J Psychiatr Res 2021 May 18;137:14-21. Epub 2021 Feb 18.

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China; Shanghai Mental Health Center, Shanghai Key Laboratory of Psychiatry Disorders, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Recent evidence supports an association between lipid metabolism dysfunction and the pathology of schizophrenia which has led to the search for peripheral blood-based biomarkers. The purpose of this study was to investigate the proteins involved in lipid metabolism (especially apolipoprotein) and to explore their potential as biomarkers for schizophrenia. Using multiple reaction monitoring mass spectrometry (MRM-MS), we quantified 22 proteins in serum samples of 109 healthy controls (HCs) and 111 patients with schizophrenia (SCZ), who were divided into discovery and validation sets. We found serum apolipoprotein A4 (ApoA4) to be significantly decreased in SCZ patients compared to HCs (p=1.61E-05). Moreover, the serum ApoA4 level served as an effective diagnostic tool, achieving area under the receiver operating characteristic curves (AUROC) of 0.840 in the discovery set and 0.791 in the validation set. Additionally, apolipoprotein F (ApoF), angiotensinogen (AGT), and alpha1-antichymotrypsin (ACT) levels were significantly higher in patients with schizophrenia than in healthy controls. These proteins combined with ApoA4, provided higher diagnostic accuracy for schizophrenia in the discovery set (AUROC=0.901) and in the validation set (AUROC=0.879). Our results suggest that the serum level of ApoA4 is a novel potential biomarker for schizophrenia. The proteins identified in this study expand the pool of biomarker candidates for schizophrenia and may be linked to the underlying mechanism of the disease.
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http://dx.doi.org/10.1016/j.jpsychires.2021.02.016DOI Listing
May 2021

CNR1 may reverse progesterone-resistance of endometrial cancer through the ERK pathway.

Biochem Biophys Res Commun 2021 Apr 25;548:148-154. Epub 2021 Feb 25.

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong Province, China. Electronic address:

Endocrine therapy is a promising treatment for endometrial cancer (EC) that preserves fertility, however, progesterone-resistance is currently the major challenges. The Cancer Genome Atlas (TCGA) database analysis showed that CNR1 was closely have a negative correlation with overall survival (OS) and relapse-free survival (RFS) in endometrial cancer. To explore the role of CNR1 in progesterone resistance and possible molecular regulation mechanism, we established stable progesterone-resistant cell lines (IshikawaPR) via progesterone tolerance of ordinary cancer cells (Ishikawa). The difference of CNR1 level in two cell lines was assessed by MTT, RT-PCR, Western blot, immunofluorescence. Then, lentiviruses constructed CNR1-knockdown with GV248 as the tool vector were used to transfect IshikwaPR cells, and the changes of biological behavior and progesterone sensitivity was verified respectively through plate cloning experiment, EdU assay, flow cytometry cycle analysis, transwell, Scratch test, etc. We founded after CNR1 was knocked down, the proliferative activity and ability to migrate of IshikawaPR cells decreased, progesterone-response sensitivity could be improved. Moreover, knockdown of CNR1 can also down-regulate ERK and NFκ B expression and activation. Furthermore, subcutaneous xenograft in nude mice was tested similarly in vivo. The above datas suggest that targeting CNR1 may reverse the progesterone resistance in endometrial cancer and may coordinate the role of ERK pathway activation.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.038DOI Listing
April 2021

A Retrospective Study of Factors Associated with Restoration of Thoracic Kyphosis in 43 Patients with Adolescent Idiopathic Scoliosis with Lenke Type 1 Curvature.

Med Sci Monit 2021 Feb 20;27:e929149. Epub 2021 Feb 20.

Department of Spine Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).

BACKGROUND This retrospective study aimed to identify the factors associated with successful surgical correction of thoracic kyphosis (TK) in 43 patients with adolescent idiopathic scoliosis (AIS) with Lenke type 1 curvature, in which the major curve with the largest Cobb angle was mainly in the thoracic region. MATERIAL AND METHODS We collected data from patients with Lenke 1 AIS. The following parameters were measured: Cobb angle, side-bending Cobb angle, cervical lordosis (CL), TK, lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), the sagittal vertical axis (SVA), the center of a C7 plumb line to the center sacral vertical line (C7-CSVL), correction rate, Ponte osteotomy, flexibility, and screw density. Univariate analysis and multivariate logistic regression analyses were performed. RESULTS Among the 43 cases analyzed, the mean postoperative Cobb angle at the last follow-up, C7-CSVL, SVA, CL, TK, LL, PI, SS, and PT were respectively 21.33±9.47°, 10.41±8.45 mm, 19.68±14.33 mm, 16.19±7.45°, 23.12±7.45°, 50.33±11.37°, 49.70±9.83°, 39.42±8.11°, and 10.16±6.63°. Univariate analysis suggested that preoperative TK, preoperative LL, and Ponte osteotomy were statistically significant (P<0.05), and multivariate analysis suggested that preoperative LL and Ponte osteotomy were statistically significant (P<0.05). CONCLUSIONS The results of this study demonstrated that preoperative TK, preoperative LL, and Ponte osteotomy were related factors for maintaining normal TK. Multivariate analysis suggested that preoperative LL and the use of Ponte osteotomy with full-thickness segmental resection of the spinal posterior column resulted in the successful surgical correction of TK in patients with AIS with Lenke type 1 curvature.
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http://dx.doi.org/10.12659/MSM.929149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903848PMC
February 2021

Valuation of SF-6Dv2 Health States in China Using Time Trade-off and Discrete-Choice Experiment with a Duration Dimension.

Pharmacoeconomics 2021 May 18;39(5):521-535. Epub 2021 Feb 18.

School of Health and Related Research, University of Sheffield, Sheffield, UK.

Objectives: Our objective was to generate a value set for the SF-6Dv2 using time trade-off (TTO) and a discrete-choice experiment with a duration dimension (DCE) in China.

Methods: A large representative sample of the Chinese general population was recruited from eight provinces/municipalities in China, stratified by age, sex, education level, and proportion of urban/rural residence. Respondents completed eight TTO tasks and ten DCE tasks during face-to-face interviews. Ordinary least squares (OLS), random-effects, fixed-effects, and Tobit models were used for TTO data, and conditional logit and mixed logit models were used for DCE. The monotonicity of model coefficients and the consistency of the predicted values according to intraclass correlation coefficient (ICC), mean absolute difference (MAD), and mean squared difference (MSD) were compared between the two approaches.

Results: In total, 3320 respondents (50.3% male; range 18-90 years) were recruited. The random-effects model and the conditional logit model were preferred for the TTO and DCE, respectively. The TTO values ranged from - 0.277 to 1, with 927 (4.94%) states considered as worse than dead (WTD). The corresponding range for DCE was - 0.535 to 1, with a higher WTD of 8.50%. DCE presented minor non-monotonicity with the coefficients in two dimensions. Values from the two approaches were highly consistent (ICC 0.9804, MAD 0.0588, MSD 0.0055), albeit those with DCE were slightly lower than those with TTO. The value set generated by TTO was preferred given the better monotonicity and the statistical significance of coefficients.

Conclusions: The Chinese value set for the SF-6Dv2 was established based on the TTO approach, but the DCE also performed well. Minor issues of non-monotonicity did present for DCE.
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http://dx.doi.org/10.1007/s40273-020-00997-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079294PMC
May 2021

Efficacy and safety of an innovatively modified cutting seton technique for the treatment of high anal fistula: A protocol for a randomized controlled trial.

Medicine (Baltimore) 2021 Feb;100(5):e24442

Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu province.

Background: Anal fistula is a common anorectal disease. So far, operation is still the optimal method to cure anal fistula. High anal fistula (HAF) is an even more clinically difficult disease to treat. Evidence suggested that seton placement can be a definitive treatment for HAF. However, tightening the seton brings great pain to patients, which affects the clinical application of the therapy. Also, this may lead to difficulty in controlling anal fluids and gas because of the larger scar left and the local defect in the anal after the operation. We propose an innovative seton technique for the treatment of HAF, after long term attempts, the operation of the modified seton cutting technique. The aim of our present study is to compare the difference of anal function, healing time, pain severity, recurrence, and complications between the procedure of the modified seton cutting technique and the conventional cutting seton operation against HAF with a randomized, controlled, prospective study.

Methods: 204 participants in this trial will be randomly divided into treatment group (procedure of the modified seton cutting technique) and control group (cutting seton technique) in a 1:1 ratio. The outcomes of continence state, pain severity after tightening, complete healing of fistula, duration to healing, operation time, recurrence rates, and postoperative complications will be recorded at 1, 2, 3, 4 weeks, then every month in the outpatient clinic. Data will be analyzed by SPSS version 22.

Conclusions: The findings of the study will help to explore the efficacy and safety of the procedure of the modified seton cutting technique against AF.

Trial Registration Number: DOI 10.17605/OSF.IO/V6G2S.
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http://dx.doi.org/10.1097/MD.0000000000024442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870255PMC
February 2021