181 results on '"Weihong Ge"'
Search Results
2. Plasma Proteomic Analysis Based on 4D-DIA Evaluates the Clinical Response to Imrecoxib in the Early Treatment of Osteoarthritis
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Han Xie, Yuan Zhang, Zunyi Zhu, Jingxuan Wei, Gulinigeer Ainiwaer, and Weihong Ge
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Osteoarthritis ,Imrecoxib ,Proteomics ,Biomarkers ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) are the primary treatment for osteoarthritis (OA), but prolonged use has adverse effects and varying efficacy. Among NSAIDs, imrecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, reduces side effects yet remains ineffective for half of the patient population. This study aims to identify biomarkers for early evaluation of imrecoxib efficacy in OA for personalized therapy optimization. Methods From September 2021 to January 2022, imrecoxib was administered to patients with OA at Nanjing Drum Tower Hospital. Plasma samples from these patients underwent proteomic analysis through the four-dimensional data-independent acquisition (4D-DIA) method, followed by bioinformatics analysis. Potential differentially expressed proteins (DEPs) were validated using enzyme-linked immunosorbent assays (ELISA). Results Sixty-six patients with knee OA were included and divided into responders (n = 35) and non-responders (n = 31). Proteomic analysis was conducted on 15 patients from each group, with ELISA validation for every patient. We found 140 DEPs between the two groups after imrecoxib treatment, characterized by 29 proteins showing upregulation and 111 displaying downregulation (P ± 1.2). Galectin-1 (LGALS1), galectin-3 (LGALS3), and cluster of differentiation 44 (CD44) were identified as potential markers for evaluating clinical response to imrecoxib in OA following ELISA validation. Conclusion This study successfully identified biomarkers for evaluating imrecoxib’s clinical response in patients with OA using 4D-DIA technology. These biomarkers may play a vital role in future personalized OA treatment strategies, pending further confirmation.
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- 2024
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3. Population pharmacokinetics, dosing optimization and clinical outcomes of biapenem in patients with sepsis
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Dayu Chen, Xuanyu Wu, Haixia Zhang, Huimin Yao, Lu Jin, Xuemei Luo, Jinchun Liu, Zejun Wu, Yuanchen Li, Wei Xu, Weihong Ge, Xingkai Chen, and Huaijun Zhu
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biapenem ,pharmacokinetics ,dosing regimen ,sepsis ,Monte Carlo simulation ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Introduction: Biapenem is a carbapenem antibiotic widely used in Asia, can be used for the treatment of adults and children with infections due to susceptible bacteria. Although biapenem is utilized in the treatment of a diverse range of bacterial infections, current pharmacokinetic data in the context of septic populations remain limited. Consequently, our research aims to evaluate the pharmacokinetics and efficacy of biapenem within a septic population to optimize biapenem therapy.Methods: In this study, we characterized the pharmacokinetics of biapenem in septic patients using a population pharmacokinetic (PPK) approach. The clinical PK data to develop the PPK model were obtained from 317 septic patients admitted to Nanjing Drum Tower Hospital between 2018 and 2022. All patients were randomized to the modeling and validation cohorts at a 3:1 ratio, with PPK modeling and validation performed utilizing the NONMEM software.Results: The model found to best describe the available data was a two-compartment PPK model with first-order elimination characterized by the parameters clearance (CL), central volume (V1), peripheral volume (V2), and intercompartmental clearance (Q). A covariate analysis identified that creatinine clearance (CLCR) was a significant covariate influencing biapenem CL, while blood urea nitrogen (BUN) was a significant covariate influencing biapenem Q. Accoding to the clinical outcome analyses, 70% of the time that the free antimicrobial drug concentration exceeds the MIC (fT>MIC) is associated with favourable clinical outcomes. The PPK model was then used to perform Monte Carlo simulations to evaluate the probability of attaining 70% fT>MIC.Conclusions: A final PPK model of biapenem was established for patients with sepsis. The current daily dosage regimen of 1.2 g may insufficient to achieve 70% fT>MIC in septic patients. The dosage regimen of 600 mg every 6 h appears to be the optimal choice.
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- 2024
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4. Acute kidney injury interacts with VKORC1 genotype on initiative warfarin dose among heart surgery recipients: a real-world research
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Liang Xiong, Feng Yu, Weihong Ge, and Hang Xu
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Medicine ,Science - Abstract
Abstract Patients who receive heart valve surgery need anticoagulation prophylaxis to reduce the risk of thrombosis. Warfarin often is a choice but its dosage varies due to gene and clinical factors. We aim to study, among them, if there is an interaction between acute kidney injury and two gene polymorphisms from this study. We extracted data of heart valve surgery recipients from the electronic health record (EHR) system of a medical center. The primary outcome is about the average daily dose of warfarin, measured as an additive interaction effect (INTadd) between acute kidney injury (AKI) and warfarin-related gene polymorphisms. The confounders, including age, sex, body surface area (BSA), comorbidities (i.e., atrial fibrillation [AF], hypertension [HTN], congestive heart failure [CHF]), serum albumin level, warfarin-relevant gene polymorphism (i.e., CYP2C9, VKORC1), prosthetic valve type (i.e., metal, bio), and warfarin history were controlled via a multivariate-linear regression model. The study included 200 patients, among whom 108 (54.00%) are female. Further, the mean age is 54.45 years, 31 (15.50%) have CHF, and 40 (20.00%) patients were prescribed concomitant amiodarone, which potentially overlays with the warfarin prophylaxis period. During the follow-up, AKI occurred in 30 (15.00%) patients. VKORC1 mutation (1639G>A) occurred in 25 (12.50%) patients and CYPC29 *2 or *3 mutations presented in 20 patients (10.00%). We found a significant additive interaction effect between AKI and VKORC1 (− 1.17, 95% CI − 1.82 to − 0.53, p = 0.0004). This result suggests it is probable that there is an interaction between acute kidney injury and the VKORC1 polymorphism for the warfarin dose during the initial period of anticoagulation prophylaxis.
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- 2023
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5. Engineered Exosomes Biopotentiated Hydrogel Promote Hair Follicle Growth via Reprogramming the Perifollicular Microenvironment
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Hairui Zhang, Jiali Yao, Qianyang Jiang, Yurou Shi, Weihong Ge, and Xiaoling Xu
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androgenetic alopecia ,flexible liposomes ,engineered exosomes ,hair follicle ,reprogram the perifollicular microenvironment ,Pharmacy and materia medica ,RS1-441 - Abstract
Androgenetic alopecia (AGA) is a highly prevalent condition in contemporary society. The conventional treatment of minoxidil tincture is hindered by issues such as skin irritation caused by ethanol, non-specific accumulation in hair follicles, and short retention due to its liquid form. Herein, we have developed a novel minoxidil-incorporated engineered exosomes biopotentiated hydrogel (Gel@MNs) that has the capability to modulate the perifollicular microenvironment for the treatment of AGA. Leveraging the exceptional skin penetration abilities of flexible liposomes and the targeting properties of exosomes, the encapsulated minoxidil can be effectively delivered to the hair follicles. In comparison to free minoxidil, Gel@MNs demonstrated accelerated hair regeneration in an AGA mouse model without causing significant skin irritation. This was evidenced by an increase in both the number and size of hair follicles within the dermal layer, enhanced capillary formation surrounding the follicles, and the regulation of the transition of hair follicle cells from the telogen phase to the anagen growth phase. Therefore, this safe and microenvironment-modifying hybrid exosome-embedded hydrogel shows promising potential for clinical treatment of AGA.
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- 2024
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6. A descriptive pharmacokinetic/pharmacodynamic analysis of ceftazidime‐avibactam in a case series of critically ill patients with augmented renal clearance
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Ying Xu, Jian Tang, Binbin Yuan, Xuemei Luo, Pei Liang, Ning Liu, Danjiang Dong, Lu Jin, Weihong Ge, and Qin Gu
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augmented renal clearance ,ceftazidime‐avibactam ,critically ill patients ,drug concentration ,pharmacodynamics ,pharmacokinetics ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract To describe the pharmacokinetics/pharmacodynamics (PK/PD) of a 2 h infusion of ceftazidime‐avibactam (CAZ‐AVI) in critically ill patients with augmented renal clearance (ARC). A retrospective review of all critically ill patients with ARC who were treated with CAZ‐AVI between August 2020 and May 2023 was conducted. Patients whose 12‐h creatinine clearance prior to CAZ‐AVI treatment and steady‐state concentration (Css) of CAZ‐AVI were both monitored were enrolled. The free fraction (fCss) of CAZ‐AVI was calculated from Css. The joint PK/PD targets of CAZ‐AVI were considered optimal when a Css/minimum inhibitory concentration (MIC) ratio for CAZ ≥4 (equivalent to 100% fT > 4 MIC) and a Css/CT ratio of AVI >1 (equivalent to 100% fT > CT 4.0 mg/L) were reached simultaneously, quasioptimal when only one of the two targets was reached, and suboptimal when neither target was reached. The relationship between PK/PD goal achievement, microbial eradication and the clinical efficacy of CAZ‐AVI was evaluated. Four patients were included. Only one patient achieved optimal joint PK/PD targets, while the other three reached suboptimal targets. The patient with optimal PK/PD targets achieved microbiological eradication, while the other three patients did not, but all four patients achieved good clinical efficacy. Standard dosages may not enable most critically ill patients with ARC to reach the optimal joint PK/PD targets of CAZ‐AVI. Optimal drug dose adjustment of CAZ‐AVI in ARC patients requires dynamic drug concentration monitoring.
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- 2024
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7. Analysis of Quality Differences in Radix Dipsaci before and after Processing with Salt Based on Quantitative Control of HPLC Multi-Indicator Components Combined with Chemometrics
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Hangsha Wu, Yue Lv, Rui Tang, Mingfang Zhao, Yafei Li, Feiyang Wei, Changyu Li, Weihong Ge, and Weifeng Du
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Analytical chemistry ,QD71-142 - Abstract
Radix Dipsaci (RD) is the dry root of the Dipsacus asper Wall. ex DC., which is commonly used for tonifying the kidney and strengthening bone. The purpose of this study was to analyze the difference between raw and salt-processed RD from the chemical composition comprehensively. The fingerprints of raw and salt-processed RD were established by HPLC-DAD to determine the contents of loganin (LN), asperosaponin VI (AVI), caffeic acid (CaA), dipsanoside A (DA), dipsanoside B (DB), chlorogenic acid (CA), loganic acid (LA), isochlorogenic acid A (IA), isochlorogenic acid B (IB), and isochlorogenic acid C (IC). The results showed that after processing with salt, the components with increased contents were LA, CaA, DA, and AVI, and the components with decreased contents were CA, LN, IB, IA, IC, and DB. Then, the chemometric methods such as principal component analysis (PCA) and fisher discriminant analysis (FDA) were used to evaluate the quality of raw and salt-processed RD. In the classification of raw and salt-processed RD, the order of importance of each chemical component was LA > DB > IA > IC > IB > LN > CA > DA > AVI > CaA. These integrated methods successfully assessed the quality of raw and salt-processed RD, which will provide guidance for the development of RD as a clinical medication.
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- 2024
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8. Analysis of Factors Influencing Whole Blood Hydroxychloroquine Concentration in Patients with Systemic Lupus Erythematosus in China
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Xuan Huang, Qing Shu, Xuemei Luo, Weihong Ge, Han Xie, and Yujie Zhou
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Hydroxychloroquine ,Systemic lupus erythematosus ,Blood concentration ,Analysis of influencing factors ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Introduction The aim of this study was to determine the factors associated with the concentrations of hydroxychloroquine (HCQ) and its major metabolite, desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE). Methods Patients with SLE taking oral HCQ for at least 3 months were recruited from the Department of Rheumatology and Immunology of Nanjing Drum Tower Hospital. Clinical characteristics and laboratory values were examined. The concentrations of HCQ and DHCQ were measured by high-performance liquid chromatography, and the effects of various factors on the concentrations were investigated. Results A total of 272 patients were included in this study. The average concentration of HCQ was 690.90 ng/ml and the average concentration of DHCQ was 431.84 ng/ml. Multivariate analysis indicated that gender (P = 0.015), age (year) (P
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- 2023
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9. Physiologically‐based pharmacokinetic pharmacodynamic parent‐metabolite model of edoxaban to predict drug–drug‐disease interactions: M4 contribution
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Ruijuan Xu, Wenyuan Liu, Weihong Ge, Hua He, and Qing Jiang
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Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract This study aimed to develop a physiologically‐based pharmacokinetic pharmacodynamic (PBPK/PD) parent‐metabolite model of edoxaban, an oral anticoagulant with a narrow therapeutic index, and to predict pharmacokinetic (PK)/PD profiles and potential drug–drug‐disease interactions (DDDIs) in patients with renal impairment. A whole‐body PBPK model with a linear additive PD model of edoxaban and its active metabolite M4 was developed and validated in SimCYP for healthy adults with or without interacting drugs. The model was extrapolated to situations including renal impairment and drug‐drug interactions (DDIs). Observed PK and PD data in adults were compared with predicted data. The effect of several model parameters on the PK/PD response of edoxaban and M4 was investigated in sensitivity analysis. The PBPK/PD model successfully predicted PK profiles of edoxaban and M4 as well as anticoagulation PD responses with or without the influence of interacting drugs. For patients with renal impairment, the PBPK model successfully predicted the fold change in each impairment group. Inhibitory DDI and renal impairment had a synergistic effect on the increased exposure of edoxaban and M4, and their downstream anticoagulation PD effect. Sensitivity analysis and DDDI simulation show that renal clearance, intestinal P‐glycoprotein activity, and hepatic OATP1B1 activity are the major factors affecting edoxaban‐M4 PK profiles and PD responses. Anticoagulation effect induced by M4 cannot be ignored when OATP1B1 is inhibited or downregulated. Our study provides a reasonable approach to adjust the dose of edoxaban in several complicated scenarios especially when M4 cannot be ignored due to decreased OATP1B1 activity.
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- 2023
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10. Pharmacist-Driven Dosing Services and Pharmaceutical Care Increase Probability of Teicoplanin Target Concentration Attainment and Improve Clinical and Economic Outcomes in Non-Critically Ill Patients
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Dayu Chen, Bo Wen, Xuanyu Wu, Xinxin Zheng, Huaijun Zhu, Xingkai Chen, Dan Han, Jinchun Liu, Yunxing Liu, Jiayue Guo, Shaoshi Zhu, Haozhen Ren, Weihong Ge, and Haixia Zhang
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Teicoplanin ,Clinical pharmacist ,Pharmaceutical care ,Therapeutic drug monitoring ,MRSA ,Non-critically ill patients ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Introduction Pharmacist-driven (PD) dosing and monitoring services have been shown to improve the clinical and economic outcomes in patients treated with different antibiotics, other than teicoplanin. This study investigates the impact of PD dosing and monitoring services on the clinical and economic outcomes of non-critically ill patients receiving teicoplanin treatment. Methods A single-center retrospective study was conducted. Patients were divided into the PD group and the non-PD (NPD) group. Primary outcomes included the achievement of target serum concentration, and a composite endpoint of all-cause mortality, intensive care unit (ICU) admission, and sepsis or septic shock development during hospitalization or within 30 days of hospital admission. The cost of teicoplanin, overall medication cost, and total cost during hospital stay were also compared. Results A total of 163 patients from January to December 2019 were included and assessed. Seventy patients were assigned to the PD group and 93 to the NPD group. The PD group had a higher percentage of patients reaching the target trough concentration (54% versus 16%, p
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- 2023
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11. Construction of a pharmaceutical care mode for cancer pain patients in primary care based on the Delphi method: an effective analysis
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Han Xie, Xinyi Chen, Min Xue, Huaying Li, Yonghan Ge, and Weihong Ge
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cancer pain ,pharmaceutical care ,Delphi method ,pain management ,primary care ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Objective: Pain is one of the most common symptoms of cancer patients. Patients with advanced stages of cancer are always transferred to primary medical institutions or treated with home medication due to their specific pathophysiological characteristics. Studies have shown that continuous pharmaceutical care can improve the effectiveness and safety of drug therapy for cancer pain patients in primary care, but no relevant research has been conducted in China. Based on the Delphi method, this study aims to construct a pharmaceutical care mode for cancer pain patients and analyze its effect in drug therapy treatment in primary care in China.Methods: A pharmaceutical care mode for cancer pain patients in primary care was developed through two rounds of expert consensus. A total of 200 cancer pain patients from January 2022 to January 2023 in Nanjing Drum Tower Hospital were recruited and divided into an intervention group and control group. The self-developed pharmaceutical care mode in primary care was conducted in the intervention group, while the traditional pharmaceutical care mode was conducted in the control group. Comparisons between the groups were performed in terms of pain assessment rate, reasonable rate of pain assessment, pain score, and incidence of adverse reactions.Results: The initiative of experts in the two rounds of consultation was 100%, with an authority coefficient of 0.83. The coordination coefficient of the second round was higher than that of the first round, indicating that the consistency of expert opinions was enhanced. There were 100 cases in each group, and 12 and 8 were lost to follow-up in the intervention group and control group, respectively. Compared with the control group, the intervention group had a significantly higher pain assessment rate, a reasonable rate of pain assessment, and a significantly lower pain score and incidence of adverse reactions.Conclusion: Under the scientific and reasonable mode of pharmaceutical care for cancer pain patients at the primary level, standardized drug therapy could significantly enhance the efficacy of treatment, thereby improving the quality of life of patients.
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- 2023
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12. Genotype-guided new approach for dose optimisation of hydroxychloroquine administration in Chinese patients with SLE
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Lingyun Sun, Wei Shen, Ziyi Jin, Dandan Wang, Yizhun Zhu, Linyu Geng, Han Xie, Xin Wen, Yuchun Wang, Xuan Huang, Qing Shu, and Weihong Ge
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Objectives The study aims to investigate the impact of gene polymorphisms on blood hydroxychloroquine (HCQ) concentrations in patients with SLE and provide guidelines for individualised care.Methods 489 Chinese patients with SLE taking HCQ for more than 3 months were collected in this study. The blood HCQ, desethylhydroxychloroquine (DHCQ) and desethylchloroquine concentrations were measured. The optimal blood concentration of HCQ was determined by receiver operating characteristic curve analysis. Single nucleotide polymorphisms of metabolic enzymes involved in HCQ metabolism were genotyped and the associations with treatment effects were investigated.Results The cut-off value of HCQ was 559.67 ng/mL, with sensitivity and specificity values of 0.51 and 0.89, respectively. The TC and CC genotypes of CYP2C8 (rs7910936) were significantly related to the increase in blood HCQ concentrations, and the CYP2C8 (rs10882521) TT genotype was associated with lower blood HCQ concentrations. The DHCQ:HCQ ratio was highest in patients with the GG genotype of the CYP2D6*10 (rs1065852) polymorphism and lowest in those with the AA genotype. Patients with the CYP2C8 (rs7910936) CC genotype were more likely to achieve the optimal blood concentration (p=0.030) in HCQ 200 mg/day group and patients with the CYP2D6*10 (rs1065852) GG genotype were more likely to reach the optimal blood concentration (p=0.049) in 400 mg/day group.Conclusions Our results suggest that the optimal blood concentration of HCQ measured approximately 12–18 hours after the last dosage may be between 500 and 600 ng/mL in Chinese patients with SLE. The observed variations in HCQ concentrations between individuals can potentially be attributed to genetic polymorphisms in CYP2D6*10 (rs1065852) and CYP2C8 (rs7910936 and rs10882521). Genotypical testing of patients and regular monitoring of blood levels are recommended for optimising HCQ dosage management in Chinese patients with SLE.Trial registration number ChiCTR2300070628.
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- 2023
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13. Efficacy and Safety of Anticoagulant Therapy Versus Antiplatelet Therapy in Acute Ischemic Stroke Patients with Atrial Fibrillation
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Xiaodi Yan BS, Baoyan Wang MSc, Peng Xia BS, Chen Lan BS, Qian Wang BS, Weihong Ge MSc, Yujie Zhou MD, and Chenxiao Jiang MSc
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
The efficacy and safety of anticoagulant therapy in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF) remain uncertain. This study enrolled 431 AIS and AF patients from Nanjing Drum Tower Hospital between January 2019 and December 2021 and followed for 365 days to determine the associations between anticoagulants and clinical outcomes by assessing modified Rankin Scale (mRS) score, recurrent ischemic stroke/systemic embolism (IS/SE), all-cause mortality, intracranial hemorrhage (ICH) and major bleeding. Final analysis included 400 eligible patients and divided them into antiplatelet group (n = 191) and anticoagulant group (n = 209). Anticoagulant therapy was associated with excellent (mRS 0–1; adjusted odds ratio (aOR), 2.63; 95% confidence interval (CI), 1.61–4.30) and favorable functional outcomes (mRS 0–2; aOR, 2.82; 95% CI, 1.69–4.70) and lower risk of all-cause mortality (adjusted hazard ratio (aHR), 0.35; 95% CI, 0.21–0.57), ICH (aHR, 0.45; 95% CI, 0.23–0.87) and major bleeding (aHR, 0.51; 95% CI, 0.28–0.94), without increasing the risk of recurrent IS/SE (aHR, 0.75; 95% CI, 0.45–1.24). In conclusion, anticoagulant therapy may be a more effective and safer option than antiplatelet therapy for AIS patients with AF.
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- 2023
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14. The association between altitude and serum folate levels in Tibetan adults on the Tibetan plateau
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Shaoli Yao, Xiwen Chen, Yao Zhou, Li Xu, Qi Zhang, Shimin Bao, Huiru Feng, and Weihong Ge
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Medicine ,Science - Abstract
Abstract This study investigated the relationship between residence altitude and serum folate levels in healthy Tibetans living on the Tibetan Plateau. Participants were selected from those who underwent physical examinations at our health center between November 2019 and February 2020. Demographic characteristics and medical histories were collected, and fasting blood was tested for serum folate and other hematological indicators. The relationship between altitude and serum folate levels was analyzed using a multivariable linear regression model. Serum folate levels were associated with altitude (β = − 0.44; 95% confidence interval [CI] − 0.71; − 0.16), hemoglobin (β = − 0.01; 95% CI − 0.03; − 0.00), red blood cells (β = − 0.72; 95% CI − 1.18; − 0.27), hematocrit (β = − 0.07; 95% CI − 0.12; − 0.02), high-density lipoprotein cholesterol (β = 2.67; 95% CI 1.35; 3.98), and sex (β = 0.68; 95% CI 0.12; 1.23). Multivariate linear regression analysis revealed that altitude was negatively associated with serum folate levels. After adjusting for confounding factors, serum folate levels decreased by 0.33 ng/mL per each 500-m increase in altitude (β = − 0.33; 95% CI − 0.6; − 0.05; P = 0.022). Altitude was negatively associated with serum folate levels in Tibetan adults. The relationship between altitude and folate levels should be further explored in populations of different races and disease states. Further large-scale prospective studies should illustrate the causality of this relationship.
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- 2022
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15. Serum concentration as a predictor of tigecycline-induced hypofibrinogenemia in critically ill patients: A retrospective cohort study
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Xiaoxuan Yang, Lu Jin, Xuemei Luo, Min Wang, Huaijun Zhu, Yujie Zhou, and Weihong Ge
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Tigecycline ,Hypofibrinogenemia ,Serum concentration ,Thresholds ,Infectious and parasitic diseases ,RC109-216 - Abstract
Objectives: This study aimed to determine the thresholds of serum concentration as a predictor of tigecycline (TGC)-induced hypofibrinogenemia (HF) in critically ill patients. Methods: A retrospective cohort study was conducted in intensive care unit patients treated with TGC. The clinical data and serum concentration were extracted from the patients’ electronic medical records. Patients were divided into an HF group and a normal group according to fibrinogen value. The receiver operating characteristic curves and logistic regression were used to derive serum concentration thresholds and quantify the association between exposure thresholds and HF while adjusting for confounders. Results: In total, 100 patients were included. The receiver operating characteristic curves analysis showed that TGC concentration parameters were strongly predictive of HF. Adjusting for duration of TGC, serum concentration at the 6 hours after the dosing (C1/2) ≥ 0.645 mg/l, area under the concentration-time curve over a 24-hour period (AUC 0-24) ≥ 20.76 mg·h/l, and serum concentration of 30 minutes before next dose (Cmin) ≥ 0.455 mg/l were associated with a three- to five-fold increased risk of TGC-induced HF in logistic regression. Conclusion: The findings from this study provide evidence that TGC exposure is highly predictive of HF, with an approximately three- to five-fold increased risk. Serum concentration at the 6 hours after the dosing (C1/2) ≥ 0.645 mg/l with best area under the receiver operating characteristic curve and negative predictive value appears to be the most appropriate toxicity threshold.
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- 2022
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16. External validation of vancomycin population pharmacokinetic models in ten cohorts of infected Chinese patients
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Ying Zhou, Enwu Long, Tianlu Shi, Zhuo Wang, Jun Zhao, Hua Liu, Yang Lin, Mingyan Jiang, Haiyan Lao, Weihong Ge, and Yimin Cui
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External validation ,Vancomycin ,Predictive performance ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: Appropriate dosage of vancomycin is critical for safety and efficacy in treating infectious diseases. Various population pharmacokinetic (PPK) models have been established. To lay a foundation for the clinical application, it is important to perform external validation of the published model. The aim of this study was to find the most suitable vancomycin PPK model for treatment of infection in China amongst all studied models developed for adults. Methods: A systematic literature search of published population vancomycin pharmacokinetic analyses was performed using the PubMed database. The identified models were evaluated in ten independent cohorts from China. Nonlinear mixed-effects modeling (NONMEM) was used for data analysis. The median prediction error (MPE), the distribution of prediction error (PE), and normalized prediction distribution errors (NPDE) were calculated and described. Predictive performance was evaluated by bias and accuracy. Results: A total of 449 vancomycin concentrations from 397 infected participants were used for external validation. The MPE of the three models from the Chinese population was less than 10%. Half of the models had an acceptable MPE. For patients with different site infections and different renal functions, each model differed in its predictive ability to some extent. The NPDE results showed that all models had an obvious bias. Conclusions: None of the models had good performance in both prediction- and simulation-based diagnostics. Carrying out sufficient external validation of the PPK model before clinical application is of utmost importance. In clinical practice, the model's population closest to the application population should be used.
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- 2022
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17. Pharmacist-led iodinated contrast media infusion risk assessment service
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Huiyan Jiang, Yuan Li, Xiaoyan Wu, Hongming Yu, Xin Zhang, Weihong Ge, and Simin Yan
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iodinated contrast media ,pharmacist ,multidisciplinary ,risk assessment ,contrast-enhanced computed tomography ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: With the increasing development of medical imaging, the use of iodinated contrast media has become more widespread. Adverse reactions caused by iodinated contrast media have drawn much attention. Despite this, there is still a lack of unified standards for the safe infusion process of iodinated contrast media in clinical practice both domestically and internationally.Objectives: Establishing a risk management service system to better predict the risks associated with iodinated contrast media infusion, reduce the incidence of adverse reactions and minimize patient harm.Method: A prospective interventional study was carried out from April 2021 to December 2021 at Nanjing Drum Tower Hospital in China. During this study, a service system was established to manage the risks associated with the infusion of iodinated contrast media. Personalized risk identification and assessment were performed by a pharmacist-led multidisciplinary team before iodinated contrast media infusion. Early warning, prevention, and adverse reaction management were performed according to different risk levels during and after infusion.Results: A multidisciplinary team led by pharmacists was established to evaluate the risks associated with infusion of iodinated contrast media. A total of 157 patients with risk factors related to the iodinated contrast media were screened out, which prevented 22 serious adverse events and enhanced the quality of medical care. All participants expressed high satisfaction with the service.Conclusion: Through practical exploration, the pharmacist-led multidisciplinary team can provide advance warning and effectively limit the risks of adverse reactions caused by iodinated contrast media to a preventable and controllable level. This approach serves as a valuable reference for developing strategies and schemes to reduce the incidence of such reactions. Therefore, we encourage the implementation of this intervention in other areas of China.
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- 2023
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18. Luteolin directly binds to KDM4C and attenuates ovarian cancer stemness via epigenetic suppression of PPP2CA/YAP axis
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Yunzhe Li, Yunran Hu, Lingling Yang, Jingshu Liu, Chenxi Cui, Muyao Yang, Dongling Zou, Lei Zhou, Qi Zhou, Weihong Ge, and Tingyuan Lang
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Luteolin ,Ovarian cancer ,Cancer stem cells ,KDM4C ,PPP2CA ,YAP ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Long-term use of low-toxic natural products holds the promise for eradicating cancer stem cells. In this study, we report that luteolin, a natural flavonoid, attenuates the stemness of ovarian cancer stem cells (OCSCs) by directly binding to KDM4C and epigenetic suppression of PPP2CA/YAP axis. Ovarian cancer stem like cells (OCSLCs) isolated by suspension culture and CD133 + ALDH+ cell sorting was employed as OCSCs model. The maximal non-toxic dose of luteolin suppressed stemness properties, including sphere-forming capacity, the expression of OCSCs markers, sphere-initiating and tumor-initiating capacities, as well as the percentage of CD133 + ALDH+ cells of OCSLCs. Mechanistic study showed that luteolin directly binds to KDM4C, blocks KDM4C-induced histone demethylation of PPP2CA promoter, inhibits PPP2CA transcription and PPP2CA-mediated YAP dephosphorylation, thereby attenuating YAP activity and the stemness of OCSLCs. Furthermore, luteolin sensitized OCSLCs to traditional chemotherapeutic drugs in vitro and in vivo. In summary, our work revealed the direct target of luteolin and the underlying mechanism of the inhibitory effect of luteolin on the stemness of OCSCs. This finding thus suggests a novel therapeutic strategy for eradicating human OCSCs driven by KDM4C.
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- 2023
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19. Prognostic performance of the NRS2002, NUTRIC, and modified NUTRIC to identify high nutritional risk in severe acute pancreatitis patients
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Dayu Chen, Bing Zhao, Linyu Wang, Yusi Qiu, Enqiang Mao, Huiqiu Sheng, Feng Jing, Weihong Ge, Xiaolan Bian, Erzhen Chen, and Juan He
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severe acute pancreatitis ,NRS 2002 ,NUTRIC score ,mNUTRIC score ,nutritional risk ,intensive care unit ,Nutrition. Foods and food supply ,TX341-641 - Abstract
BackgroundAcute pancreatitis (AP) is the most common gastrointestinal disease requiring hospital admission. AP patients are categorized as mild, moderately severe, and severe AP (SAP). For SAP patients, malnutrition increases susceptibility to infection and mortality. The Nutritional Risk Screening 2002 (NRS 2002), the Nutrition Risk in Critically Ill (NUTRIC) score and modified Nutrition Risk in Critically Ill (mNUTRIC) are nutritional risk screening tools of critically ill patients and have not been validated in patients with SAP. It is essential to evaluate the prognostic performance of these nutritional risk screening tools.Materials and methodsA retrospective study was designed to validate the NRS 2002, NUTRIC, and mNUTRIC when applied to SAP patients. Receiver operating characteristic curves were plotted to investigate the predictive ability of clinical outcomes by comparing areas under the curve (AUC). Appropriate cut-offs were calculated by using Youden’s index. Patients were identified as being at high nutritional risk according to the calculated cut-off values. The effects of different scoring systems on mortalities were calculated using the Cox proportional hazards model. Logistic regression was used to assess the association between the energy provision and 28-day mortality.ResultsFrom January 2013 to December 2019, 234 SAP patients were included and analyzed. Patients categorized as high nutritional risk by the NRS 2002 (12.6% versus 1.9% for 28-day and 20.5% versus 3.7% for 90-day), NUTRIC (16.2% versus 0.0% for 28-day and 27.0% versus 0.0% for 90-day), and mNUTRIC (16.4% versus 0.0% for 28-day and 26.4% versus 0.8% for 90-day) had significant higher mortality than those categorized as low nutritional risk. The NUTRIC (AUC: 0.861 for 28-day mortality and 0.871 for 90-day mortality, both cut-off value ≥3) and mNUTRIC (AUC: 0.838 for 28-day and 0.828 for 90-day mortality, both cut-off value ≥3) showed better predictive ability of the 28- and 90-day mortality than the NRS 2002 (AUC: 0.706 for 28-day mortality and 0.695 for 90-day mortality, both cut-off value ≥5).ConclusionThe NRS 2002, NUTRIC, and mNUTRIC scores were predictors for the 28- and 90-day mortalities. The NUTRIC and mNUTRIC showed better predictive ability compared with the NRS 2002 when applied to SAP patients.
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- 2023
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20. Risk Factors for Granulocytopenia in Patients with Graves’ Disease Receiving Antithyroid Drugs
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Jiaxi Li, Xiaowen Zhang, Lintong Li, Qiaoling Zhu, Weihong Ge, and Cheng Ji
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Objective. To study the risk factors for granulocytopenia caused by antithyroid drugs. Methods. Patients who were diagnosed with Graves’ hyperthyroidism and regularly treated with antithyroid drugs (ATDs) from January 2010 to July 2022 at Nanjing Drum Tower Hospital, aged >18 years, were selected for general information and laboratory tests and divided into two groups according to the occurrence of granulocytopenia. Independent risk factors for the development of granulocytopenia in patients treated with ATDs were analyzed using one-way and multiway logistic regression analyses, and the predictive value of each index was evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results. A total of 818 patients were enrolled, of which 95 developed granulocytopenia. Univariate analysis revealed that sex, white blood cell (WBC) counts, neutrophil-to-lymphocyte ratio (NLR), glutamic-pyruvic transaminase (ALT), aspartate transaminase (AST), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) before medication were risk factors for ATD-induced granulocytopenia (P
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- 2023
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21. Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury
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Chen Li, Zhourui Wu, Liqiang Zhou, Jingliang Shao, Xiao Hu, Wei Xu, Yilong Ren, Xingfei Zhu, Weihong Ge, Kunshan Zhang, Jiping Liu, Runzhi Huang, Jing Yu, Dandan Luo, Xuejiao Yang, Wenmin Zhu, Rongrong Zhu, Changhong Zheng, Yi Eve Sun, and Liming Cheng
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Medicine ,Biology (General) ,QH301-705.5 - Abstract
Abstract Spinal cord injury (SCI) involves diverse injury responses in different cell types in a temporally and spatially specific manner. Here, using single-cell transcriptomic analyses combined with classic anatomical, behavioral, electrophysiological analyses, we report, with single-cell resolution, temporal molecular and cellular changes in crush-injured adult mouse spinal cord. Data revealed pathological changes of 12 different major cell types, three of which infiltrated into the spinal cord at distinct times post-injury. We discovered novel microglia and astrocyte subtypes in the uninjured spinal cord, and their dynamic conversions into additional stage-specific subtypes/states. Most dynamic changes occur at 3-days post-injury and by day-14 the second wave of microglial activation emerged, accompanied with changes in various cell types including neurons, indicative of the second round of attacks. By day-38, major cell types are still substantially deviated from uninjured states, demonstrating prolonged alterations. This study provides a comprehensive mapping of cellular/molecular pathological changes along the temporal axis after SCI, which may facilitate the development of novel therapeutic strategies, including those targeting microglia.
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- 2022
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22. Association between hyperuricemia and metabolic syndrome: A cross-sectional study in Tibetan adults on the Tibetan plateau
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Shaoli Yao, Yao Zhou, Li Xu, Qi Zhang, Shimin Bao, Huiru Feng, and Weihong Ge
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hyperuricemia ,metabolic syndrome ,Tibetan plateau ,components of metabolic syndrome ,Tibetan adults ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
PurposeThis study aimed to assess the relationship of serum uric acid with metabolic syndrome and its components in Tibetan adults on the Tibetan plateau.MethodsA total of 307 participants were enrolled in this study and biochemical parameters including serum uric acid, fasting plasma glucose, white blood cell, lymphocyte count, mononuclear cells, alanine aminotransferase, aspartate aminotransferase, creatinine, and lipid profile were analyzed using standard methods. The IDF criteria were applied to define metabolic syndrome. The association of serum uric acid with metabolic syndrome and its components was evaluated by multivariable logistic regression models.ResultsThe overall prevalence of metabolic syndrome was 17.3% (53/307) with 19.6% (31/158) in females and 14.8% (22/149) in male participants. The prevalence of hyperuricemia was 40.7% (125/307) with significant differences between the male (53.7%,80/149) and female (28.5%,45/158) groups. In regression analysis, we observed that the risk of MetS was higher in participants in the hyperuricemia group (adjusted OR, 4.01; 95% CI, 2.02~7.99) compared with those in the normouricemia group. After adjusting for all confounding factors, a 9% higher risk of MetS could be shown in participants with SUA increased per 10umol/L (adjusted OR, 1.09; 95% CI, 1.04~1.14). These relationships were not affected by sex or age (p >0.05). After adjusting for the confounding factors, hyperuricemia is positively associated with abdominal obesity (adjusted OR, 2.53; 95% CI, 1.41~4.53), elevated blood pressure (adjusted OR, 2.61; 95% CI, 1.37~4.97), and elevated triglycerides(adjusted OR, 2.47; 95% CI, 1.09~5.57).ConclusionsIn our study, hyperuricemia is significantly associated with the prevalence of metabolic syndrome and part of its components, and these relationships are not affected by sex or age. Given the high prevalence of MetS and hyperuricemia among Tibetan adults, more studies are required to explore the role of SUA in the pathogenesis of MetS.
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- 2022
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23. Plasma metabolomic profiling reveals factors associated with dose-adjusted trough concentration of tacrolimus in liver transplant recipients
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Huaijun Zhu, Min Wang, Xiaofu Xiong, Yao Du, Danying Li, Zhou Wang, Weihong Ge, and Yizhun Zhu
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liver transplantation ,tacrolimus ,metabolomics ,therapeutic drug monitoring ,trough concentration ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Inter- and intrapatient variability of tacrolimus exposure is a vital prognostic risk factor for the clinical outcome of liver transplantation. New factors or biomarkers characterizing tacrolimus disposition is essential for optimal dose prediction in recipients of liver transplant. The aim of the study was to identify potential plasma metabolites associated with the dose-adjusted trough concentration of tacrolimus in liver transplant recipients by using a global metabolomic approach. A total of 693 plasma samples were collected from 137 liver transplant recipients receiving tacrolimus and regular therapeutic drug monitoring. Untargeted metabolomic analysis was performed by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. Univariate and multivariate analyses with a mixed linear model were conducted, and the results showed that the dose-adjusted tacrolimus trough concentration was associated with 31 endogenous metabolites, including medium- and long-chain acylcarnitines such as stearoylcarnitine (β = 0.222, p = 0.001), microbiota-derived uremic retention solutes such as indolelactic acid (β = 0.194, p = 0.007), bile acids such as taurohyodeoxycholic acid (β = −0.056, p = 0.002), and steroid hormones such as testosterone (β = 0.099, p = 0.001). A multiple linear mixed model including 11 metabolites and clinical information was established with a suitable predictive performance (correlation coefficient based on fixed effects = 0.64 and correlation coefficient based on fixed and random effects = 0.78). These data demonstrated that microbiota-derived uremic retention solutes, bile acids, steroid hormones, and medium- and long-chain acylcarnitines were the main metabolites associated with the dose-adjusted trough concentration of tacrolimus in liver transplant recipients.
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- 2022
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24. Comprehensive metabolomic characterization of atrial fibrillation
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Chengcan Lu, Chunyan Liu, Di Mei, Mengjie Yu, Jian Bai, Xue Bao, Min Wang, Kejia Fu, Xin Yi, Weihong Ge, Jizhong Shen, Yuzhu Peng, and Wei Xu
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atrial fibrillation ,metabolomics ,diagnostic model ,risk factors ,biomarker ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundUsing human humoral metabolomic profiling, we can discover the diagnostic biomarkers and pathogenesis of disease. The specific characterization of atrial fibrillation (AF) subtypes with metabolomics may facilitate effective and targeted treatment, especially in early stages.ObjectivesBy investigating disturbed metabolic pathways, we could evaluate the diagnostic value of biomarkers based on metabolomics for different types of AF.MethodsA cohort of 363 patients was enrolled and divided into a discovery and validation set. Patients underwent an electrocardiogram (ECG) for suspected AF. Groups were divided as follows: healthy individuals (Control), suspected AF (Sus-AF), first diagnosed AF (Fir-AF), paroxysmal AF (Par-AF), persistent AF (Per-AF), and AF causing a cardiogenic ischemic stroke (Car-AF). Serum metabolomic profiles were determined by gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Metabolomic variables were analyzed with clinical information to identify relevant diagnostic biomarkers.ResultsThe metabolic disorders were characterized by 16 cross-comparisons. We focused on comparing all of the types of AF (All-AFs) plus Car-AF vs. Control, All-AFs vs. Car-AF, Par-AF vs. Control, and Par-AF vs. Per-AF. Then, 117 and 94 metabolites were identified by GC/MS and LC-QTOF-MS, respectively. The essential altered metabolic pathways during AF progression included D-glutamine and D-glutamate metabolism, glycerophospholipid metabolism, etc. For differential diagnosis, the area under the curve (AUC) of specific metabolomic biomarkers ranged from 0.8237 to 0.9890 during the discovery phase, and the predictive values in the validation cohort were 78.8–90.2%.ConclusionsSerum metabolomics is a powerful way to identify metabolic disturbances. Differences in small–molecule metabolites may serve as biomarkers for AF onset, progression, and differential diagnosis.
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- 2022
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25. The protective capability of Hedyotis diffusa Willd on lupus nephritis by attenuating the IL-17 expression in MRL/lpr mice
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Ying Li, Tao Ding, Jing Chen, Jinjun Ji, Weijie Wang, Bin Ding, Weihong Ge, Yongsheng Fan, and Li Xu
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Hedyotis diffusa Willd ,lupus nephritis ,network pharmacology ,interleukin-17 ,STAT3 ,inflammation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Lupus nephritis (LN), the most severe organ manifestation of systemic lupus erythematosus (SLE), is generally treated with glucocorticoids (GC) in clinical practice, leading to drug resistance and adverse effects in the long term. Fortunately, the combination of GC and traditional Chinese medical prescriptions can attenuate the adverse effects and improve therapeutic efficiency. Hedyotis diffusa Willd (HDW) is one of the most commonly used herbal compounds for LN treatment, which exhibits “heat-clearing” and “detoxification” effects. However, the underlying pharmacological mechanism remains unclear. The present study identified the chemical compounds in HDW extract with UPLC-Q-TOF-MS/MS. A total of 49 components were identified in the HDW extract, and the IL-17 signaling pathway was highly enriched by network pharmacological analysis. MRL/lpr model mice, reflecting the spontaneous development of LN, were used to evaluate the protective activity and investigate the underlying mechanism of the combination treatment. The white blood cell content (WBC), including lymphocytes and neutrophils, cytokines (IL-6, MCP-1, TNF-a), and various autoantibodies (ANA, ab-dsDNA, ab-snRNP/sm) in the blood of MRL/lpr mice were significantly improved by the intragastric administration of HDW. Additionally, the expression of STAT3, IL-17, Ly6G, and MPO in the kidney and neutrophil NETosis were ameliorated with HDW treatment. The pathological and morphological analysis suggested that HDW application could reduce urinary protein levels and inflammatory cell infiltration and inhibit glomerular interstitial cell proliferation. Hence, HDW might ameliorate lupus nephritis by inhibiting IL-6 secretion and STAT3-induced IL-17 expression. The active compounds in HDW were predictively selected with computational methods. The docking affinity of asiatic acid, neoandrographolide to IL-6, glycyrrhetinic acid, oleanolic acid, ursolic acid, and wilforlide A to STAT3 are extremely high. In conclusion, the IL-6 and STAT3/IL-17signaling pathways could be critical regulative targets of HDW on LN.
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- 2022
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26. Predictive Factors for Acute Postoperative Pain After Open Radical Gastrectomy for Gastric Cancer
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Han Xie, Jingxuan Wei, Zhengliang Ma, and Weihong Ge
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gastric cancer ,surgery ,postoperative ,acute pain ,predictor ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundPain has become an important factor in evaluating patients' quality of life and clinical treatment. For gastric cancer (GC) patients, open radical gastrectomy (OG) causes significant trauma to the body, increases patients' pain after operation, and delays early recovery. The aim of this study was to investigate the predictive factors of acute pain after OG within postoperative 72 h.MethodsFrom March 2020 to September 2021, 307 patients who underwent OG were included in the study in Nanjing Drum Tower Hospital. The predictors included demographic predictors, pathological data, surgical predictors, and intraoperative predictors. The pain scores at 12, 24, 48, and 72 h after operation were evaluated by numeric rating scale (NRS). The predictors of acute pain were determined by univariate and multivariate analysis.ResultsThe average pain score (NRS) of patients showed a downward trend over time within 72 h after OG. Multivariate analysis indicated that total gastrectomy (OR 1.823, 95% CI 1.094–3.040, P < 0.05), AJCC TNM stage (II) (OR.232, 95% CI 0.062–0.872, P < 0.05), AJCC TNM stage(III) (OR.185, 95% CI 0.049–0.698, P < 0.05), BMI (kg/m2) (OR 1.75, 95% CI 1.029–2.976, P < 0.05), distant metastasis (OR 3.054, 95% CI 1.019–9.155, P < 0.05), intraoperative transfusion (OR 2.246, 95% CI 1.267–3.982, P < 0.01) were significant predictive factors for acute pain after OG.ConclusionReasonable postoperative acute pain control was the prerequisite for accelerating the postoperative rehabilitation of patients. In order to reduce the occurrence of excessive or insufficient analgesia, it was necessary for patients who underwent OG to formulate appropriate analgesics according to risk factors.
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- 2022
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27. Drug-Induced Hospital-Acquired Acute Kidney Injury in China: A Multicenter Cross-Sectional Survey
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Chen Liu, Suying Yan, Yuqin Wang, Jinwei Wang, Xiujuan Fu, Hongtao Song, Rongsheng Tong, Mei Dong, Weihong Ge, Jiawei Wang, Hui Yang, Changlian Wang, Peiyuan Xia, Limei Zhao, Sijing Shen, Juan Xie, Yangui Xu, Peizhi Ma, Hongjian Li, Shegui Lu, Yufeng Ding, Ling Jiang, Yang Lin, Maoyi Wang, Feng Qiu, Wanyu Feng, and Li Yang
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drug-induced acute kidney injury ,hospital-acquired acute kidney injury ,Internal medicine ,RC31-1245 - Abstract
Introduction: Drug-induced acute kidney injury (D-AKI) is one of the important types of AKI. The incidence of D-AKI in China has rarely been studied. Objective: This study aims to explore the disease burden, related drugs, and risk factors of D-AKI. Methods: A nationwide cross-sectional survey was conducted in adult patients from 23 academic hospitals in 17 provinces in China. Suspected AKI was screened based on serum creatinine changes in accordance with the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for AKI, patients who met the diagnosis of hospital-acquired AKI in January and July of 2014 were defined. Suspected AKI was firstly evaluated for the possibility of D-AKI by pharmacists using the Naranjo Scale and finally defined as D-AKI by nephrologists through reviewing AKI clinical features. Results: Altogether 280,255 hospitalized patients were screened and 1,960 cases were diagnosed as hospital-acquired AKI, among which 735 cases were defined as having D-AKI (37.50%, 735/1,960) with an in-hospital mortality rate of 13.88% and 54.34% of the survivors did not achieve full renal recovery. 1,642 drugs were related to AKI in these patients. Anti-infectives, diuretics, and proton pump inhibitors were the top 3 types of drugs relevant to D-AKI, accounting for 66.63% cumulatively. Besides age, AKI staging, severe disease, hypoalbuminemia, plasma substitute, and carbapenem related D-AKI were independent risk factors for in-hospital mortality of D-AKI patients. Conclusion: In China, D-AKI has caused a substantial medical burden. Efforts should be made to pursue nephrotoxic drug stewardship to minimize attributable risk and improve the prevention, diagnosis, and treatment of D-AKI.
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- 2020
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28. Graded and pan-neural disease phenotypes of Rett Syndrome linked with dosage of functional MeCP2
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Xiaoying Chen, Xu Han, Bruno Blanchi, Wuqiang Guan, Weihong Ge, Yong-Chun Yu, and Yi E. Sun
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MeCP2 ,Rett Syndrome ,human pluripotent stem cell ,neural differentiation ,Cytology ,QH573-671 ,Animal biochemistry ,QP501-801 - Abstract
Abstract Rett syndrome (RTT) is a progressive neurodevelopmental disorder, mainly caused by mutations in MeCP2 and currently with no cure. We report here that neurons from R106W MeCP2 RTT human iPSCs as well as human embryonic stem cells after MeCP2 knockdown exhibit consistent and long-lasting impairment in maturation as indicated by impaired action potentials and passive membrane properties as well as reduced soma size and spine density. Moreover, RTT-inherent defects in neuronal maturation could be pan-neuronal and occurred in neurons with both dorsal and ventral forebrain features. Knockdown of MeCP2 led to more severe neuronal deficits as compared to RTT iPSC-derived neurons, which appeared to retain partial function. Strikingly, consistent deficits in nuclear size, dendritic complexity and circuitry-dependent spontaneous postsynaptic currents could only be observed in MeCP2 knockdown neurons but not RTT iPSC-derived neurons. Both neuron-intrinsic and circuitry-dependent deficits of MeCP2-deficient neurons could be fully or partially rescued by re-expression of wild type or T158M MeCP2, strengthening the dosage dependency of MeCP2 on disease phenotypes and also the partial function of the mutant. Our findings thus reveal stable neuronal maturation deficits and unexpectedly, graded sensitivities of neuron-inherent and neural transmission phenotypes towards the extent of MeCP2 deficiency, which is informative for future therapeutic development.
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- 2020
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29. Chinese-Named Entity Recognition From Adverse Drug Event Records: Radical Embedding-Combined Dynamic Embedding–Based BERT in a Bidirectional Long Short-term Conditional Random Field (Bi-LSTM-CRF) Model
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Hong Wu, Jiatong Ji, Haimei Tian, Yao Chen, Weihong Ge, Haixia Zhang, Feng Yu, Jianjun Zou, Mitsuhiro Nakamura, and Jun Liao
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Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
BackgroundWith the increasing variety of drugs, the incidence of adverse drug events (ADEs) is increasing year by year. Massive numbers of ADEs are recorded in electronic medical records and adverse drug reaction (ADR) reports, which are important sources of potential ADR information. Meanwhile, it is essential to make latent ADR information automatically available for better postmarketing drug safety reevaluation and pharmacovigilance. ObjectiveThis study describes how to identify ADR-related information from Chinese ADE reports. MethodsOur study established an efficient automated tool, named BBC-Radical. BBC-Radical is a model that consists of 3 components: Bidirectional Encoder Representations from Transformers (BERT), bidirectional long short-term memory (bi-LSTM), and conditional random field (CRF). The model identifies ADR-related information from Chinese ADR reports. Token features and radical features of Chinese characters were used to represent the common meaning of a group of words. BERT and Bi-LSTM-CRF were novel models that combined these features to conduct named entity recognition (NER) tasks in the free-text section of 24,890 ADR reports from the Jiangsu Province Adverse Drug Reaction Monitoring Center from 2010 to 2016. Moreover, the man-machine comparison experiment on the ADE records from Drum Tower Hospital was designed to compare the NER performance between the BBC-Radical model and a manual method. ResultsThe NER model achieved relatively high performance, with a precision of 96.4%, recall of 96.0%, and F1 score of 96.2%. This indicates that the performance of the BBC-Radical model (precision 87.2%, recall 85.7%, and F1 score 86.4%) is much better than that of the manual method (precision 86.1%, recall 73.8%, and F1 score 79.5%) in the recognition task of each kind of entity. ConclusionsThe proposed model was competitive in extracting ADR-related information from ADE reports, and the results suggest that the application of our method to extract ADR-related information is of great significance in improving the quality of ADR reports and postmarketing drug safety evaluation.
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- 2021
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30. Correction to: Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury
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Chen Li, Zhourui Wu, Liqiang Zhou, Jingliang Shao, Xiao Hu, Wei Xu, Yilong Ren, Xingfei Zhu, Weihong Ge, Kunshan Zhang, Jiping Liu, Runzhi Huang, Jing Yu, Dandan Luo, Xuejiao Yang, Wenmin Zhu, Rongrong Zhu, Changhong Zheng, Yi Eve Sun, and Liming Cheng
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Medicine ,Biology (General) ,QH301-705.5 - Published
- 2022
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31. Distribution Evaluation of Tenofovir in the Breast Milk of Mothers With HBeAg-Positive Chronic HBV Infection After Treatment With Tenofovir Alafenamide and Tenofovir Disoproxil Fumarate by a Sensitive UPLC-MS/MS Method
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Na Yang, Guanlun Zhou, Xiaoliang Cheng, Jun He, Yan Chen, Chao Chen, Meijuan Li, Jiajia Ge, Min Wang, Tianqi Zhang, Weihong Ge, Huaijun Zhu, and Guorong Han
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tenofovir alafenamide ,tenofovir ,breast milk ,UPLC—MS /MS ,HBV ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir (TFV) that has been approved for the treatment of chronic hepatitis B virus (HBV) infection. It has greater plasma stability and more favorable renal safety than tenofovir disoproxil fumarate (TDF), the first approved oral prodrug of TFV. However, the distribution of TFV in the breast milk of mothers treated with TAF is still unclear. In this study, sixteen participants with chronic HBV infection were enrolled and received antiretroviral therapy with 25 mg of TAF or 300 mg of TDF daily from 24 to 28 weeks of gestation until the 4th week postpartum. For the first time, the distribution of TFV in the breast milk of mothers with chronic HBV infection treated with TAF and its difference from TDF were evaluated by using a sensitive UPLC–MS/MS method. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C18 column (1.7 µm 2.1 × 100 mm). Mass spectrometry analysis was performed in positive electrospray ionization mode and multiple reaction monitoring (MRM) conditions of transitions m/z 288.1→176.2 for TFV. This method was linear from 0.5 to 500 ng/ml. Surprisingly, on the third postpartum day, the median Cmax of TFV in the breast milk was much higher in the mothers treated with TAF (101.2 ng/ml) than TDF (21.6 ng/ml) at a similar Tmax of 4 h. Accordingly, the median AUC0-8 value was 755.6 ng h/mL in the mothers taking TAF, which was at a 5-fold higher level than TDF. The concentration of TFV in the breast milk of mothers in both groups decreased with increasing lactation time. These data indicated that there was a relatively higher exposure of TFV in the breast milk of mothers taking TAF, despite the lower dosage compared to TDF. This study provides support for further evaluating the safety of breastfeeding after the administration of TAF and TDF.
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- 2021
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32. Effects of Tranexamic Acid on Hemorrhage Control and Deep Venous Thrombosis Rate After Total Knee Arthroplasty: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
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Tao Ling, Zhihu Zhao, Wenwen Xu, Weihong Ge, and Lingli Huang
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total knee arthroplasty ,network meta-analysis ,total blood loss ,deep vein thrombosis ,tranexamic acid ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Total knee arthroplasty (TKA) surgery has a lot of complications, especially hemorrhage, which can be controlled via tranexamic acid (TXA). The guidelines endorse the integration of TXA interventions in the management of TKA-induced complications. However, uncertainty surrounds the effects of different TXA therapies. This frequentist model network meta-analysis (NMA) aims to compare hemorrhage control and deep venous thrombosis (DVT) rate of different TXA therapies in TKA.Methods: Articles were searched with the PubMed, Embase, Cochrane Library, and Web of Science from 1966 to October 2020. Randomized controlled trials (RCTs) comparing different TXA therapies, or with placebo in patients with TKA were included. Two investigators independently conducted article retrievals and data collection. The outcome was total blood loss and DVT rate. Effect size measures were mean differences (MDs), or odds ratios (ORs) with 95% confidence intervals (CIs). We conducted a random-effects NMA using a frequentist approach to estimate relative effects for all comparisons and rank treatments according to the mean rank and surface under the cumulative ranking curve values. All analyses were performed in Stata software or R software. The study protocol was registered with PROSPERO, number CRD42020202404.Results: We identified 1 754 citations and included 81 studies with data for 9 987 patients with TKA. Overall, all TXA therapies were superior to placebo for total blood loss in TKA. Of all TXA therapies, M therapy (IV/IV infusion + oral TXA > 3g) was most effective for total blood loss (MD=−688.48, −1084.04–−328.93), followed by F therapy (IV TXA ≥ 15 mg/kg or 1 g three times). TXA therapies in this study are not associated with the increase of DVT risk.Conclusions: TXA therapies in this study are effective and safe for the treatment of TKA-induced complications. M therapy (IV/IV infusion + oral TXA > 3 g) may be the most effective TXA therapy for hemorrhage control. TXA therapies in this study do not increase DVT risk. Considering hemorrhage control and DVT rate simultaneously, F therapy (IV TXA ≥ 15 mg/kg or 1 g three times) may be suggested to apply for TKA, and this study may provide a crucial clue to future TXA use.
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- 2021
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33. Availability, affordability and price components of insulin products in different-level hospital pharmacies: Evidence from two cross-sectional surveys in Nanjing, China.
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Lulu Wang, Liang Dai, Hui Liu, Huizhen Dai, Xin Li, and Weihong Ge
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Medicine ,Science - Abstract
The essential medicine--insulin cannot be easily accessed and afforded in many countries. To help address this issue, we evaluated the availability, affordability and price of insulin products in Nanjing, eastern China. Two cross-sectional studies were conducted in 2016 and 2018. A total of 56 hospital pharmacies were sampled, using a simplified and adapted World Health Organization/Health Action International (WHO/HAI) methodology. Prices were expressed as Median Price Ratios (MPRs) to Australian Pharmaceutical Benefit Scheme (PBS) prices. In addition, we investigated the price components of seven selected insulin products as a case study before and after the Online Centralized Procurement Policy for Hospital Drugs in May, 2018. Affordability was presented as the number of daily wages of the lowest paid unskilled government worker (LPGW) required to purchase 1000IU of insulin based on the average courses of treatment, approximately 30 days' treatment. The availability of insulin products was very high in secondary hospitals and tertiary hospitals both in 2016 and 2018, but in community hospitals was very low. In 2018, the availability of prandial insulin products showed fluctuation compared to 2016. The availability of pre-mixed human insulin products was over 95% overall, and also very high (80%) in community hospitals in 2018. The prices of insulin products were much lower than PBS prices of Australian in this study, with the MPRs less than 1 (0.32 to 0.71 in 2016 vs. 0.30 to 0.68 in 2018) for all insulin types. But insulin products in Nanjing in 2016 and 2018 were considered unaffordable, because the number of daily wages of the LPGW needed to purchase for the 30 days treatment of insulin products ranged from 2.26 to 8.49 in 2016 and 1.88 to 7.09 in 2018. The manufacturers' selling price contributed the main part (74.15% to 77.70% before and 74.86% to 91.51% after the implementation of the bidding policy) of the price components of target insulin brands. The availability of insulin products was high in secondary hospitals and tertiary hospitals, but lower in community hospitals. However, the affordability in community hospitals was better than other hospitals, but the insulin products were still unaffordable for patients on low incomes. Further improvements of the availability accessibility and affordability of medicines in advancing health insurance policies and lowering drug prices should be put forward.
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- 2021
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34. Rapid Quality Identification of Decoction Pieces of Crude and Processed Corydalis Rhizoma by Near-Infrared Spectroscopy Coupled with Chemometrics
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Weihao Zhu, Hao Hong, Zhihui Hong, Xianjie Kang, Weifeng Du, Weihong Ge, and Changyu Li
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Analytical chemistry ,QD71-142 - Abstract
In order to identify the quality of crude and processed Corydalis Rhizoma decoction pieces, the research established a simple, fast, reliable, and validated near-infrared qualitative and quantitative model combined with chemometrics. 51 batches of crude and 40 batches of processed Corydalis Rhizoma from the Zhejiang and Jiangsu provinces of China were collected and analyzed. Crude and processed Corydalis Rhizoma samples were crushed to obtain NIR spectra. The content of seven alkaloids in crude and processed Corydalis Rhizoma was determined by high-performance liquid chromatography (HPLC). Pretreatment methods were screened such as normalization methods, offset filtering methods, and smoothing. Combined with partial least squares-discriminant analysis (PLS-DA) and partial least squares (PLS), the qualitative and quantitative models of crude and processed Corydalis Rhizoma were established, and the correlation coefficient (R2), root mean square error of calibration (RMSEC), and root mean square error of prediction (RMSEP) were used as evaluation indexes. Tetrahydropalmatine was used as an example for screening pretreatment methods; the results showed that MSC combined with the second derivative and no smoothing and the model with the wavelength range of 10000–5000 cm−1 had the best predictive ability and applied to all seven alkaloid components. Among them, the correlation coefficients were all higher than 0.99, and RMSEC and RMSEP were all less than 1%. The qualitative and quantitative model of the seven alkaloids in Corydalis Rhizoma can effectively identify the crude and processed Corydalis Rhizoma and determine the content of the seven alkaloids. By studying the NIR qualitative and quantitative models of crude and processed Corydalis Rhizoma, we can achieve rapid discrimination and quantitative prediction of crude and processed Corydalis Rhizoma. These methods can greatly improve the efficiency of traditional Chinese medicine analysis and provide a strong scientific basis for the quality identification and control of traditional Chinese medicine.
- Published
- 2021
- Full Text
- View/download PDF
35. Serum proteomics analysis of candidate predictive biomarker panel for the diagnosis of trastuzumab-based therapy resistant breast cancer
- Author
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Ting Yang, Ziyi Fu, Yin Zhang, Min Wang, Changfei Mao, and Weihong Ge
- Subjects
HER2-positive breast cancer ,Trastuzumab-based therapy resistance ,Proteomics ,Serum protein biomarkers ,LC–MS/MS ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Human epidermal growth factor receptor 2 (HER2)-positive is a particularly aggressive type of the breast cancer. Trastuzumab-based therapy is a standard treatment for HER2-positive breast cancer, but some patients are resistant to the therapy. Serum proteins have been used to predict therapeutic benefit for various cancers, but whether serum proteins can serve as biomarkers for HER2-positive breast cancer remains unclear. Using an isobaric Tandem Mass Tag (TMT) label-based quantitative proteomic, we discovered 18 differentially expressed proteins in the serum of trastuzumab-based therapy resistant patients before therapy. Then, four proteins were selected and validated using an LC–MS/MS-based multiple reaction monitoring quantification method, and it was confirmed that three proteins (SRGN, LDHA and CST3) were correlated with trastuzumab-based therapy resistance. Finally, the trastuzumab-based therapy resistance diagnostic score was calculated and acquired by means of a logistic regression pattern based on the level of these three proteins. In summary, we develop a serum-based protein signature that potentially predicts the therapeutic effects of trastuzumab-based therapy for HER2-positive breast cancer patients.
- Published
- 2020
- Full Text
- View/download PDF
36. Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in CNS function with and without injury
- Author
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Dandan Luo, Weihong Ge, Xiao Hu, Chen Li, Chia-Ming Lee, Liqiang Zhou, Zhourui Wu, Juehua Yu, Sheng Lin, Jing Yu, Wei Xu, Lei Chen, Chong Zhang, Kun Jiang, Xingfei Zhu, Haotian Li, Xinpei Gao, Yanan Geng, Bo Jing, Zhen Wang, Changhong Zheng, Rongrong Zhu, Qiao Yan, Quan Lin, Keqiang Ye, Yi E. Sun, and Liming Cheng
- Subjects
spinal cord injury repair ,immune deficiency ,transcriptomic analysis ,neurotransmision ,Cytology ,QH573-671 ,Animal biochemistry ,QP501-801 - Abstract
Abstract The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.
- Published
- 2018
- Full Text
- View/download PDF
37. Quantitative determination, principal component analysis and discriminant analysis of eight marker compounds in crude and sweated Dipsaci Radix by HPLC-DAD
- Author
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Weifeng Du, Xiaoning Li, Ying Yang, Xianke Yue, Dongjing Jiang, Weihong Ge, and Baochang Cai
- Subjects
primary processing ,quality control ,pca ,da ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Context: Dipsaci Radix is derived from the dry root of Dipsacus asper Wall.ex Henry (Dipsacaceae). It has attracted increasing attention as one of the most popular and precious herbal medicines in clinical use. Objective: To develop a HPLC-DAD method for quantitative analysis and quality control of eight active components in crude and sweated Dipsaci Radix. Materials and methods: The eight components in Dipsaci Radix were analyzed by HPLC-DAD on an Agilent Eclipse XDB-C18 column within a gradient elution of acetonitrile and 0.05% formic acid aqueous solution. ESI-MS spectra were acquired on a triple quadrupole mass spectrometer. Validation was performed in order to demonstrate linearity, precision, repeatability, stability, and accuracy of the method. The results were processed with principal component analysis (PCA) and discriminant analysis (DA). Results: The eight components showed good linearity (R2 > 0.9991) in the ranges of 60.40–1208.00, 151.00–3020.00, 3.06–61.20, 30.76–615.20, 5.13–102.60, 10.17–203.40, 10.20–204.00, and 151.60–3032.00 mg/mL, respectively. The overall recoveries were in the range of 99.03–102.38%, with RSDs ranging from 1.89% to 4.05%. Through PCA, the degree of importance of the eight components in sequence was CA > AVI > IA > LA > LN > IC > IB > CaA. The crude and sweated Dipsaci Radix were distinguished obviously by DA. Discussion and conclusion: The method, using HPLC-DAD analysis in combination with PCA and DA, could provide a more comprehensive and quantitative chemical pattern recognition and quality evaluation to crude and sweated Dipsaci Radix.
- Published
- 2017
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38. β-Elemene Synergizes With Gefitinib to Inhibit Stem-Like Phenotypes and Progression of Lung Cancer via Down-Regulating EZH2
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Haibo Cheng, Xiaoyin Ge, Shiqin Zhuo, Yanan Gao, Bo Zhu, Junfeng Zhang, Wenbin Shang, Dakang Xu, Weihong Ge, and Liyun Shi
- Subjects
elemene ,gefitinib ,lung cancer ,stemness ,EZH2 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The inhibitors for EGF receptor tyrosine kinase (EGFR-TKIs) such as gefitinib have been used as a standard treatment for non-small cell lung cancer (NSCLC), but the increasingly occurrence of drug resistance, the associated adverse effects and the enrichment of cancer stem cells significantly impedes its clinical application. β-elemene is a natural sesquiterpene with potent anti-cancer ability, and also it is renowned for its plant-origin, safety and the additive effect with traditional therapies, which prompt us to explore its potential to co-operate with TKIs to achieve greater therapeutic efficacy. Impressively, our study demonstrates that, elemene, in combination of gefitinib, displayed a significantly higher activity in inhibiting lung cancer cellular proliferation, migration and invasion. More importantly, combinative treatment profoundly impaired the epithelial to mesenchymal transition (EMT), the stem-like properties and the self-renewal capacity of lung cancer cells, and hence impeded the in vivo tumor development. We also reveal that the synergistic anti-tumor effect of elemene and gefitinib was largely mediated their regulation of enhancer of zeste homolog 2 (EZH2), an oncogenic histone methyltransferase and gene transcriptional regulator. Thus, our data indicate that combinative treatment of elemene and gefitinib has greater anti-neoplastic activity and greater efficacies in targeting cancer stem-like properties, mainly through regulating the malignant gene modifier and hence the subsequent effector molecules required for cancer progression. The findings may have potential implications for treating aggressive and resistant lung cancers.
- Published
- 2018
- Full Text
- View/download PDF
39. NUDT15 R139C Variants Increase the Risk of Azathioprine-Induced Leukopenia in Chinese Autoimmune Patients
- Author
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Xiang Fei, Qing Shu, Huaijun Zhu, Bingzhu Hua, Shiying Wang, Ling Guo, Yun Fang, and Weihong Ge
- Subjects
azathioprine ,NUDT15 R139C ,leukopenia ,Chinese ,autoimmune patients ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The aim of this study was to investigate the influence of NUDT15 R139C, thiopurine S-methyltransferase (TPMT), and 6-TGN on azathioprine (AZA) induced leukopenia in Chinese autoimmune patients. Among 87 enrolled patients, 23 (26.4%) had leukopenia. The NUDT15 R139C variant was associated with leukopenia (p = 1.86 × 10−7; OR: 7.59; 95% CI: 3.16–18.21). However, TPMT genotype was not shown to be correlated with the incidence of leukopenia (p = 0.95). There was no significant difference of 6-TGN concentration between patients with or without leukopenia (p = 0.15) and no association was found in patients with NUDT15 R139C variants alleles (p = 0.62). Finally, we found that the range of 6-TGN concentrations in autoimmune diseases was much lower than the established 6-TGN monitoring range for inflammatory bowel diseases. Therefore, the variant of NUDT15 R139C is strongly associated with AZA-induced leukopenia in Chinese patients with various autoimmune diseases such as systemic lupus erythematosus, Sjögren's syndrome, etc.
- Published
- 2018
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40. Simultaneous quantification of seven B vitamins in human faeces by stable isotope label-based high-performance liquid chromatography-tandem mass spectrometry
- Author
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XIA, Yu, primary, Cheng, JI, additional, Meijuan, LI, additional, ZHANG, Wei, additional, CHENG, Xiaoliang, additional, QIU, Yanyan, additional, and Weihong, GE, additional
- Published
- 2023
- Full Text
- View/download PDF
41. Evidence‐based guideline for the prevention and management of perioperative infection
- Author
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Qiaoyu Wang, Mingnan Cao, Hua Tao, Zhimin Fei, Xiufeng Huang, Pixia Liang, Baiyun Liu, Jianping Liu, Xiaoyang Lu, Penglin Ma, Shuyi Si, Shuo Wang, Yuewei Zhang, Yingli Zheng, Lei Zang, Xiao Chen, Zhanjun Dong, Weihong Ge, Wei Guo, Xin Hu, Xin Huang, Ling Li, Jianshu Liang, Baoge Liu, Dong Liu, Linna Liu, Songqing Liu, Xianghong Liu, Liyan Miao, Haixia Ren, Guangzhi Shi, Luwen Shi, Shumei Sun, Xia Tao, Rongsheng Tong, Cheng Wang, Bin Wang, Jincheng Wang, Jingwen Wang, Xiaoling Wang, Xiaoyan Wang, Jian Xie, Shouxia Xie, Hua Yang, Jianxin Yang, Chao You, Hongyi Zhang, Yi Zhang, Chengson Zhao, Qingchun Zhao, Jiangguo Zhu, Bo Ji, Ruichen Guo, Chunhua Hang, Xiaowei Xi, Sheyu Li, Zhicheng Gong, Jianxin Zhou, Rui Wang, and Zhigang Zhao
- Subjects
Health Policy ,General Medicine - Published
- 2023
42. The Therapeutic Potential of Antioxidants in Chemotherapy-Induced Peripheral Neuropathy: Evidence from Preclinical and Clinical Studies
- Author
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Lin Zhou, Hui Yang, Jing Wang, Yunxing Liu, Yinqiu Xu, Hang Xu, Yong Feng, and Weihong Ge
- Subjects
Pharmacology ,Pharmacology (medical) ,Neurology (clinical) - Published
- 2023
43. Effectiveness and safety of path‐based analgesic regimens designed by clinical pharmacists based on the type of biliary and pancreatic surgery
- Author
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Han Xie, Xinmei Wang, Min Xue, Yudong Qiu, and Weihong Ge
- Subjects
Pharmacology ,Pharmacology (medical) - Abstract
As the incidence of postoperative pain in patients with biliary and pancreatic diseases has gradually increased, how to control postoperative pain has received increasing research attention. By reading pain management guidelines and multidisciplinary communication and cooperation, clinical pharmacists designed multi-mode analgesia regimens based on surgical types, in order to provide strong evidence for the effectiveness and safety of postoperative analgesia regimens and better serve patients.Data from biliary or pancreatic surgery performed at Nanjing Drum Tower Hospital from 2019 to 2021 were collected. Take October 2020 as the time point to compare the outcomes before and after the implementation of the path-based postoperative analgesic regimens. The primary outcomes were NRS pain scores, sleep quality, and incidence of adverse reactions. Length of stay was a secondary outcome.A total of 268 and 239 patients were enrolled in the study and control groups, respectively. Four path-based postoperative analgesic management regimens significantly reduced patients' static and dynamic NRS scores in the 24 h (p 0.05). The patients' sleep quality were better than controls (p 0.05). The incidence of adverse reactions and the length of stay in the study group were numerically lower than controls. Moderate analysis indicated that four analgesia regimens are more precise and better meet actual clinical needs.Effective and safe postoperative pain management is particularly important for clinical purposes. Path-based postoperative analgesia regimens based on different types of surgery overcome the disadvantages of overly broad and generalized traditional guidelines, which play an important role in providing personalized and precise clinical services. Further, study findings provide evidence that four path-based analgesic regimens can reduce postoperative pain and reduce the length of hospital stay, which may provide a better direction for clinical postoperative pain management.
- Published
- 2022
44. Steroid Hormone Profiling in Hyperandrogenism and Non-hyperandrogenism Women with Polycystic Ovary Syndrome
- Author
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Jiajia, Ge, Na, Yang, Xiaoli, Zhang, Meijuan, Li, Wei, Zhang, Jun, He, Huaijun, Zhu, Xiaoliang, Cheng, Shanmei, Shen, and Weihong, Ge
- Subjects
Tandem Mass Spectrometry ,Androstenedione ,Humans ,Obstetrics and Gynecology ,Female ,Testosterone ,Steroids ,Luteinizing Hormone ,Hyperandrogenism ,Polycystic Ovary Syndrome ,Chromatography, Liquid - Abstract
The purpose of this study is to explore the differences in the steroid metabolic network between hyperandrogenic and non-hyperandrogenic women with polycystic ovary syndrome (PCOS). A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for the quantification of 36 kinds of serum steroids in 80 PCOS women during their follicular phase. Compared with those in non-hyperandrogenemia PCOS women (NA-PCOS), the levels of 17-hydroprogesterone (P = 0.009), androstenedione (P 0.001), total testosterone (P 0.001), dihydrotestosterone (P = 0.025), estrone (P = 0.007), and estradiol (P 0.001) were increased in hyperandrogenemia PCOS (HA-PCOS) women. It was suggested that HA-PCOS may have increased activity of P450c17 (17-hydropregnenolone/pregnenolone, P = 0.008), 3βHSD2 (androstenedione/dehydroepiandrosterone, P = 0.004), and 17βHSD3 (testosterone/dehydroepiandrosterone, P = 0.01) and decreased activity of 5α reductase (dihydrotestosterone/testosterone, P = 0.008). Moreover, the ratio of luteinizing hormone (LH) to follicle stimulating hormone (FSH) was found to be related to these increased steroids and enzyme activities. In conclusion, the HA-PCOS and the NA-PCOS women showed different steroid profiles, and the different enzyme activities in steroidogenic pathway may be the main reason for the difference.
- Published
- 2022
45. Physiologically‐based pharmacokinetic pharmacodynamic parent‐metabolite model of edoxaban to predict drug–drug‐disease interactions: <scp>M4</scp> contribution
- Author
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Ruijuan Xu, Wenyuan Liu, Weihong Ge, Hua He, and Qing Jiang
- Subjects
Modeling and Simulation ,Pharmacology (medical) - Published
- 2023
46. Copper Increases the Sensitivity of Cholangiocarcinoma Cells to Tripterine by Inhibiting TMX2‐Mediated Unfolded Protein Reaction Activation
- Author
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Hongwen Liu, Lei Xu, Yiyang Zhang, Yiqiong Xie, Lishan Wang, Yue Zhou, Zhangding Wang, Yani Pan, Wenying Li, Lu Xu, Xinyun Xu, Ting Wang, Kui Meng, Jian He, Yudong Qiu, Guifang Xu, Weihong Ge, Yun Zhu, and Lei Wang
- Subjects
Biomaterials ,Biomedical Engineering ,Pharmaceutical Science - Published
- 2023
47. Population Pharmacokinetics of Voriconazole and Dose Optimization in Chinese Elderly Patients
- Author
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Jing Wang, Yue Shen, Zejun Wu, huaijun zhu, and Weihong Ge
- Abstract
Objectives: This study aimed to establish a population pharmacokinetic model for elderly individuals receiving intravenous voriconazole, and to assess and optimize the dosing regimens using a simulating approach. Methods: A population pharmacokinetic analysis was conducted using the NONMEN software based on 438 plasma concentrations from 150 elderly patients receiving multiple intravenous doses of voriconazole. The individualized optimal dosage regimen was proposed based on the obtained population pharmacokinetics parameters. The final model was assessed by the goodness of fit plots, non-parametric bootstrap method, and visual predictive check. Monte Carlo simulations were carried out to assess and optimize the dosing regimens with a therapeutic range of 2.0-5.0 mg/L as the target plasma trough concentration (Cmin). Results: A one-compartment model with first-order absorption and elimination fitted well to the concentration-time profile of voriconazole. The typical voriconazole clearance was 3.55 L/h, and the typical volume of distribution was 194 L. Covariate analysis indicated that the CL of voriconazole was substantially influenced by albumin (ALB), gamma glutamyl transpeptidase, and direct bilirubin, while the volume was associated with body weight. Conclusions: The first study on the population pharmacokinetics of voriconazole in Chinese elderly people was performed. Individualized dosing regimens were recommended for different ALB levels based on population PK model prediction. The proposed dosing regimens could provide a rationale for dosage individualization to improve clinical outcomes and minimize drug-related toxicities.
- Published
- 2023
48. Silymarin ameliorates peritoneal fibrosis by inhibiting the TGF-β/Smad signaling pathway
- Author
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Yingwen Bai, Lulu Wang, null TingYang, Lingyun Wang, and Weihong Ge
- Subjects
Pharmacology ,General Medicine - Published
- 2023
49. Drug-drug interaction extraction via hybrid neural networks on biomedical literature.
- Author
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Hong Wu, Yan Xing, Weihong Ge, Xiaoquan Liu, Jianjun Zou, Changjiang Zhou, and Jun Liao
- Published
- 2020
- Full Text
- View/download PDF
50. Research on the effect of Dipsaci Radix before and after salt-processed on kidney yang deficiency syndrome rats and the preliminary mechanism study through the BMP-Smad signaling pathway
- Author
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Weifeng Du, Yue Lv, Hangsha Wu, Yafei Li, Rui Tang, Mingfang Zhao, Feiyang Wei, Changyu Li, and Weihong Ge
- Subjects
Pharmacology ,Drug Discovery - Published
- 2023
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