1.Phlorizin Ameliorates Glucose and Lipid Metabolism Disorders in T2DM Rats by Modulating IRS-1/PI3K/Akt Signaling Pathway
Nuer AILI ; Qingyu CAO ; Huan LIU ; Junwei HE ; Weihong ZHONG ; Lan CAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):139-148
ObjectiveTo observe the pharmacodynamic efficacy of phlorizin in improving hepatic glycolipid metabolism disorders in type 2 diabetic mellitus (T2DM) rats and to explore its mechanism of action based on the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodsA high-fat diet and streptozotocin (STZ) were used to establish T2DM rat models. The rats were randomly assigned into six groups: the blank control group, model group, metformin group (300 mg·kg-1), and phlorizin high-dose (100 mg·kg-1) and low-dose groups (25 mg·kg-1). The rats were given intragastric administration for 6 weeks. The changes in body weight and fasting blood glucose (FBG) were observed, and the oral glucose tolerance test (OGTT) was carried out. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glycated serum protein (GSP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in serum were detected by an automatic biochemical analyzer. The levels of fasting insulin (FINS), interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by the biochemical assays. The pancreas index, liver index, and insulin resistance index were calculated. Hematoxylin-eosin (HE) staining was used to evaluate the pathological changes in liver and pancreatic tissues. The immunofluorescence method was used to detect the changes in insulin and glucagon in pancreatic tissue. Western blot was used to detect the expression of related proteins in the IRS-1/PI3K/Akt pathway of liver tissue and its downstream glycogen synthase kinase-3β (GSK-3β) and forkhead box transcription factor O1 (FoxO1) proteins. ResultsCompared with the blank control group, the body weight of rats in the model group continued to decrease, while the FBG level increased significantly. The area under the OGTT blood glucose curve (AUC), GSP, TC, TG, LDL-C, IL-1β, IL-6, TNF-α, MDA, pancreatic index and liver index increased significantly, while the levels of HDL-C, SOD, and FINS decreased significantly (P0.05, P0.01). Histological results showed that the pancreatic islets of rats in the model group exhibited atrophy and severe structural abnormalities. The insulin-positive β-cells decreased significantly (P0.01), while the glucagon-positive α-cells increased significantly (P0.01). Inflammatory cell infiltration and partial necrosis were observed in the liver tissues of the model group rats. The expressions of p-IRS-1/IRS-1, p-GSK-3β/GSK-3β, and p-FoxO1/FoxO1 proteins in the liver of the model group increased significantly (P0.01), while the expressions of p-PI3K/PI3K and p-Akt/Akt proteins decreased significantly (P0.01). Compared with the model group, the diabetic symptoms of rats in all administration groups were improved. The changes in body weight and FBG were close to those of the blank control group. The levels of OGTT-AUC, GSP, TC, TG, LDL-C, MDA, IL-1β, IL-6, TNF-α and the pancreatic index, liver index were obviously reduced (P0.05, P0.01), while the levels of HDL-C, SOD, and FINS obviously increased (P0.05, P0.01). The pathological changes of the pancreas and liver in rats in all treatment groups were effectively improved. The insulin-positive β-cells in the pancreas increased significantly (P0.01), while the glucagon-positive α-cells decreased significantly (P0.01). The protein expressions of p-IRS-1/IRS-1, p-GSK-3β/GSK-3β, and p-FoxO1/FoxO1 in the liver were significantly reduced (P0.01), while the protein expressions of p-PI3K/PI3K and p-Akt/Akt significantly increased (P0.01). ConclusionPhlorizin reversed the weight loss and abnormal increase of FBG in T2DM rats, improved blood lipid profiles, oxidative stress, and inflammatory levels, alleviated insulin resistance, and had certain protective effects on the liver and pancreas. The hypoglycemic mechanism may involve regulating the IRS-1/PI3K/Akt signaling pathway to inhibit the activities of GSK-3β and FoxO1, thereby promoting liver glycogen synthesis and suppressing hepatic gluconeogenesis, ultimately improving glycolipid metabolism disorders.
2.Phlorizin Ameliorates Glucose and Lipid Metabolism Disorders in T2DM Rats by Modulating IRS-1/PI3K/Akt Signaling Pathway
Nuer AILI ; Qingyu CAO ; Huan LIU ; Junwei HE ; Weihong ZHONG ; Lan CAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):139-148
ObjectiveTo observe the pharmacodynamic efficacy of phlorizin in improving hepatic glycolipid metabolism disorders in type 2 diabetic mellitus (T2DM) rats and to explore its mechanism of action based on the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodsA high-fat diet and streptozotocin (STZ) were used to establish T2DM rat models. The rats were randomly assigned into six groups: the blank control group, model group, metformin group (300 mg·kg-1), and phlorizin high-dose (100 mg·kg-1) and low-dose groups (25 mg·kg-1). The rats were given intragastric administration for 6 weeks. The changes in body weight and fasting blood glucose (FBG) were observed, and the oral glucose tolerance test (OGTT) was carried out. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glycated serum protein (GSP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in serum were detected by an automatic biochemical analyzer. The levels of fasting insulin (FINS), interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by the biochemical assays. The pancreas index, liver index, and insulin resistance index were calculated. Hematoxylin-eosin (HE) staining was used to evaluate the pathological changes in liver and pancreatic tissues. The immunofluorescence method was used to detect the changes in insulin and glucagon in pancreatic tissue. Western blot was used to detect the expression of related proteins in the IRS-1/PI3K/Akt pathway of liver tissue and its downstream glycogen synthase kinase-3β (GSK-3β) and forkhead box transcription factor O1 (FoxO1) proteins. ResultsCompared with the blank control group, the body weight of rats in the model group continued to decrease, while the FBG level increased significantly. The area under the OGTT blood glucose curve (AUC), GSP, TC, TG, LDL-C, IL-1β, IL-6, TNF-α, MDA, pancreatic index and liver index increased significantly, while the levels of HDL-C, SOD, and FINS decreased significantly (P0.05, P0.01). Histological results showed that the pancreatic islets of rats in the model group exhibited atrophy and severe structural abnormalities. The insulin-positive β-cells decreased significantly (P0.01), while the glucagon-positive α-cells increased significantly (P0.01). Inflammatory cell infiltration and partial necrosis were observed in the liver tissues of the model group rats. The expressions of p-IRS-1/IRS-1, p-GSK-3β/GSK-3β, and p-FoxO1/FoxO1 proteins in the liver of the model group increased significantly (P0.01), while the expressions of p-PI3K/PI3K and p-Akt/Akt proteins decreased significantly (P0.01). Compared with the model group, the diabetic symptoms of rats in all administration groups were improved. The changes in body weight and FBG were close to those of the blank control group. The levels of OGTT-AUC, GSP, TC, TG, LDL-C, MDA, IL-1β, IL-6, TNF-α and the pancreatic index, liver index were obviously reduced (P0.05, P0.01), while the levels of HDL-C, SOD, and FINS obviously increased (P0.05, P0.01). The pathological changes of the pancreas and liver in rats in all treatment groups were effectively improved. The insulin-positive β-cells in the pancreas increased significantly (P0.01), while the glucagon-positive α-cells decreased significantly (P0.01). The protein expressions of p-IRS-1/IRS-1, p-GSK-3β/GSK-3β, and p-FoxO1/FoxO1 in the liver were significantly reduced (P0.01), while the protein expressions of p-PI3K/PI3K and p-Akt/Akt significantly increased (P0.01). ConclusionPhlorizin reversed the weight loss and abnormal increase of FBG in T2DM rats, improved blood lipid profiles, oxidative stress, and inflammatory levels, alleviated insulin resistance, and had certain protective effects on the liver and pancreas. The hypoglycemic mechanism may involve regulating the IRS-1/PI3K/Akt signaling pathway to inhibit the activities of GSK-3β and FoxO1, thereby promoting liver glycogen synthesis and suppressing hepatic gluconeogenesis, ultimately improving glycolipid metabolism disorders.
3.Effect and mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance in rats with type 2 diabetes mellitus
Yuxin HONG ; Lei ZHANG ; Mingxue ZHOU ; Sinai LI ; Li LIN ; Meng ZHANG ; Zixuan GUO ; Weihong LIU
China Pharmacy 2025;36(1):24-29
OBJECTIVE To investigate the improvement effect and potential mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance (IR) in type 2 diabetes mellitus (T2DM) rats. METHODS T2DM rat model was established by intraperitoneal injection of 30 mg/kg streptozotocin combined with high-fat and high-sugar diet. The rats were randomly divided into normal control group, model group, Qingxue xiaozhi jiangtang formula low-dose and high-dose groups (6.525, 13.05 g/kg, calculated by raw material) and metformin group (positive control, 0.18 g/kg), with 8 rats in each group. Administration groups were given relevant medicine intragastrically; normal control group and model group were given constant volume of normal saline intragastrically, once a day, for consecutive 6 weeks. Body mass and fasting blood glucose (FBG) were determined, and oral glucose tolerance test was conducted. Serum fasting insulin (FINS) level was measured to calculate the insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI). Additionally, the level of serum lipids, liver function, oxidative stress indicators and inflammatory factors were assessed. The phosphorylation levels of kinase R-like endoplasmic reticulum kinase (PERK) and forkhead box O1 (FOXO1) protein in liver tissue of rats were determined. RESULTS Compared with model group, the body weight, ISI, the levels of high-density lipoprotein cholesterol and superoxide dismutase were increased significantly in Qingxue xiaozhi jiangtang formula high-dose group and metformin group (P<0.05); FBG, blood glucose level at 120 minutes of glucose loading, area under the curve of glucose, FINS, HOMA-IR, low-density lipoprotein cholesterol, total cholesterol, triglyceride, alanine transaminase, aspartate transaminase, alkaline phosphatase, malondialdehyde, interleukin-6, tumor necrosis factor-α, and C-reactive protein levels were significantly reduced (P< Δ0.05); the pathological damage of liver tissue had significantlyimproved, and the phosphorylation levels of PERK and FOXO1 proteins in liver tissue were significantly decreased (P<0.05). CONCLUSIONS Qingxue xiaozhi jiangtang formula can regulate glucose and lipid metabolism, inflammation factor and oxidative stress levels, and alleviate insulin resistance in T2DM rats. Its mechanism of action may be related to the inhibition of the PERK/FOXO1 signaling pathway.
4.Impact of early detection and management of emotional distress on length of stay in non-psychiatric inpatients: A retrospective hospital-based cohort study.
Wanjun GUO ; Huiyao WANG ; Wei DENG ; Zaiquan DONG ; Yang LIU ; Shanxia LUO ; Jianying YU ; Xia HUANG ; Yuezhu CHEN ; Jialu YE ; Jinping SONG ; Yan JIANG ; Dajiang LI ; Wen WANG ; Xin SUN ; Weihong KUANG ; Changjian QIU ; Nansheng CHENG ; Weimin LI ; Wei ZHANG ; Yansong LIU ; Zhen TANG ; Xiangdong DU ; Andrew J GREENSHAW ; Lan ZHANG ; Tao LI
Chinese Medical Journal 2025;138(22):2974-2983
BACKGROUND:
While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients.
METHODS:
This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively.
RESULTS:
The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge.
CONCLUSION
Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans
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Retrospective Studies
;
Male
;
Length of Stay/statistics & numerical data*
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Female
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Middle Aged
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Adult
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Psychological Distress
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Inpatients/psychology*
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Aged
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Anxiety/diagnosis*
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Depression/diagnosis*
5.Safety and effectiveness of lecanemab in Chinese patients with early Alzheimer's disease: Evidence from a multidimensional real-world study.
Wenyan KANG ; Chao GAO ; Xiaoyan LI ; Xiaoxue WANG ; Huizhu ZHONG ; Qiao WEI ; Yonghua TANG ; Peijian HUANG ; Ruinan SHEN ; Lingyun CHEN ; Jing ZHANG ; Rong FANG ; Wei WEI ; Fengjuan ZHANG ; Gaiyan ZHOU ; Weihong YUAN ; Xi CHEN ; Zhao YANG ; Ying WU ; Wenli XU ; Shuo ZHU ; Liwen ZHANG ; Naying HE ; Weihuan FANG ; Miao ZHANG ; Yu ZHANG ; Huijun JU ; Yaya BAI ; Jun LIU
Chinese Medical Journal 2025;138(22):2907-2916
INTRODUCTION:
Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD.
METHODS:
In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging.
RESULTS:
A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline.
CONCLUSIONS:
Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies.
REGISTRATION
ClinicalTrials.gov , NCT07034222.
Humans
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Alzheimer Disease/drug therapy*
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Male
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Female
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Aged
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Middle Aged
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Cognitive Dysfunction/drug therapy*
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Aged, 80 and over
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Amyloid beta-Peptides/metabolism*
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Biomarkers
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East Asian People
6.Early effectiveness of transosseous suture fixation in treatment of recurrent acute patellar dislocation with patellar osteochondral fractures.
Junliang LIU ; Longxiang ZHAI ; Zhenmu XU ; Aoqiu WU ; Ding ZHOU ; Yuchen HE ; Qian LIU ; Qi TANG ; Weihong ZHU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(7):831-836
OBJECTIVE:
To evaluate the early effectiveness of transosseous suture fixation in treating recurrent acute patellar dislocation with patellar osteochondral fractures (OCFs).
METHODS:
A retrospective analysis was conducted on 19 patients with recurrent acute patellar dislocation and patellar OCFs, who underwent transosseous suture fixation between January 2018 and December 2022 and were followed up 2 years. The cohort included 8 males and 11 females, aged 13-21 years (mean, 16.2 years). Patients experienced 2-5 times of patellar dislocation (mean, 3.2 times). The interval from the last dislocation to operation ranged from 3 to 15 days (mean, 9.6 days). Preoperative imaging revealed the intra-articular osteochondral fragments and medial patellofemoral ligament (MPFL) injury. Clinical outcomes were evaluated using the visual analogue scale (VAS) score for pain, the International Knee Documentation Committee (IKDC) score, the Hospital for Special Surgery (HSS) knee score, the Lysholm score, and the Tegner score. Postoperative complications were recorded. During follow-up, the knee X-ray films, CT, and MRI were taken to evaluate fragment healing, displacement, and the morphology and tension of the MPFL reconstruction graft.
RESULTS:
All incisions healed primarily, and no complication occurred such as infection, joint stiffness, patellofemoral arthritis, or redislocation. Patients were followed up 24-60 months (mean, 43.5 months). At 12 months postoperatively and the last follow-up, significant improvements ( P<0.05) were observed in VAS, Lysholm, IKDC, HSS, and Tegner scores compared to preoperative values. Further improvements were observed at last follow-up compared with the 12 months postoperatively, and the differences were significant ( P<0.05). Imaging studies demonstrated satisfactory osteochondral fragment positioning with stable fixation. At last follow-up, all fragments had healed, and MPFL reconstruction grafts exhibited optimal morphology and tension. No joint adhesion or fragment displacement occurred.
CONCLUSION
For recurrent acute patellar dislocation with patellar OCFs, transosseous suture fixation proves to be both safe and effective, achieving satisfactory early effectiveness.
Humans
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Male
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Female
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Patellar Dislocation/surgery*
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Adolescent
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Young Adult
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Retrospective Studies
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Patella/surgery*
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Suture Techniques
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Treatment Outcome
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Recurrence
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Fracture Fixation, Internal/methods*
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Fractures, Bone/surgery*
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Follow-Up Studies
7.A practice guideline for therapeutic drug monitoring of mycophenolic acid for solid organ transplants.
Shuang LIU ; Hongsheng CHEN ; Zaiwei SONG ; Qi GUO ; Xianglin ZHANG ; Bingyi SHI ; Suodi ZHAI ; Lingli ZHANG ; Liyan MIAO ; Liyan CUI ; Xiao CHEN ; Yalin DONG ; Weihong GE ; Xiaofei HOU ; Ling JIANG ; Long LIU ; Lihong LIU ; Maobai LIU ; Tao LIN ; Xiaoyang LU ; Lulin MA ; Changxi WANG ; Jianyong WU ; Wei WANG ; Zhuo WANG ; Ting XU ; Wujun XUE ; Bikui ZHANG ; Guanren ZHAO ; Jun ZHANG ; Limei ZHAO ; Qingchun ZHAO ; Xiaojian ZHANG ; Yi ZHANG ; Yu ZHANG ; Rongsheng ZHAO
Journal of Zhejiang University. Science. B 2025;26(9):897-914
Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C0), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug-drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage*
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Drug Monitoring/methods*
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Humans
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Organ Transplantation
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Immunosuppressive Agents/administration & dosage*
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Delphi Technique
8.Therapeutic efficacy and mechanism of artesunate for mouse model of polycystic ovary syndrome
Xueling WANG ; Peiling ZHONG ; Zhipeng ZHAO ; Fei CHEN ; Xin LIU ; Sijia LIU ; Lie YUAN ; Lu FANG ; Qianyi YAO ; Xiong YANG ; Chao LIU ; Jiakun CHENG ; Yongqing CAI ; Xiaoli LI ; Weihong LI
Journal of Army Medical University 2025;47(3):193-204
Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P<0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P<0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P<0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P<0.05),and reduced HOMA-IR,TC and TG levels(P<0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P<0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.
9.Inhibition effect of secondary metabolites of Pseudomonas aeruginosa on Candida albicans and machanisms explore in vitro
Peng WANG ; Yuhang LUO ; Ping QIU ; Qi LI ; Jiawei LIU ; Linjuan CHEN ; Xuan CHEN ; Weihong WEN ; Lingqing XU
International Journal of Laboratory Medicine 2025;46(17):2097-2104
Objective To study the inhibitory effect of secondary metabolites of Pseudomonas aeruginosa(PA)on Candida albicans(CA)and to explore some of the mechanisms.Methods PA and CA strains were i-solated from clinical specimens from the hospital.Then,PA strains with inhibitory effects on CA were screened through cross-line test and co-incubation test,and crude extracts of PA secondary metabolites were prepared,and were tested together with pyocyanin,phenazine-1-carboxylic acid,1-hydroxyphenazine,and 3-ox-ododecyl-l-homoserine lactone(3-oxo-HSL).The inhibitory effects of various PA secondary metabolites on CA were determined through minimum inhibitory concentration test,minimum bactericidal concentration test,time-sterilization curve measurement,and XTT method activity measurement test,and some mechanisms by which PA secondary metabolites inhibited CA were explored.Results The strongest inhibitory effect on CA was 1-hydroxyphenazine,and at a concentration of 6.250 μg/mL,the relative activity of CA decreased to 0.00%.Next were pyocyanin and PA crude extract,and the relative fungal activity of CA decreased to 0.00%at concentrations of 200 and 100 μg/mL.1-hydroxyphenazine,pyocyanin,3-oxo-HSL and PA crude extract all had inhibitory effects on the formation of CA hyphae.Reactive oxygen species(ROS)were generated in CA cells treated with 1-hydroxyphenazine,phenazine 1-carboxylic acid,pyocyanin,and PA crude extract,and the highest levels of ROS were induced by pyocyanin and 1-hydroxyphenazine.Conclusion Phenazine secondary metabolites 1-hydroxyphenazine and pyocyanin have significant inhibitory effects on the growth and activity of CA,and both induce the highest amount of ROS.The quorum-sensing signal molecule 3-oxo-HSL have no in-hibitory effect on CA growth,but have a significant inhibitory effect on the formation of fungal hyphae.
10.Application of ultrasound multimodal diagnostic mode combined with ultrasonic precision interventional technology in differentiating the benign from malignant solid breast masses
Shipeng WANG ; Weihong NIE ; Junde LIU ; Yunfeng CHEN ; Caixia GUO ; Xiang LI ; Yihe ZHANG
Journal of Interventional Radiology 2025;34(1):70-74
Objective To discuss the application of ultrasound multimodal diagnostic mode combined with ultrasonic precision interventional technology in differentiating the benign from malignant solid breast masses.Methods A total of 396 patients who underwent breast surgery at the Wuwei Cancer Hospital of China from May 2021 to July 2023 were enrolled in this study.Within 2 weeks before surgery,multimodal ultrasound examination(including two-dimensional ultrasound,color Doppler ultrasound,elastic ultrasound,breast three-dimensional ultrasound,and contrast-enhanced ultrasound)and ultrasound-guided needle biopsy were performed in all patients.The consistency between the results of multimodal ultrasound examination,ultrasound-guided needle biopsy,combination diagnosis and the postoperative pathological diagnoses was analyzed.Results Of the 396 patients with solid breast mass,malignant lesion was seen in 237(59.85%)and benign lesion was seen in 159(40.15%).The sensitivity of multimodal ultrasound in diagnosing benign and malignant solid breast masses was 77.64%(184/237),the specificity was 90.57%(144/159),the positive predictive value was 92.46%(184/199),the negative predictive value was 73.10%(144/197),the accuracy was 82.83%(328/396),and the consistency with the postoperative pathological diagnosis was 0.656.The sensitivity of ultrasound-guided needle puncture in diagnosing benign and malignant solid breast masses was 94.51%(224/237),the specificity was 100.00%(159/159),the positive predictive value was 100.00%(224/224),the negative predictive value was 92.44%(159/172),the accuracy was 96.72%(383/396),and the consistency with the postoperative pathological diagnosis was 0.933.The sensitivity of multimodal ultrasound combined with ultrasound-guided needle puncture in diagnosing benign and malignant solid breast masses was 100.00%(228/228),the specificity was 94.64%(159/168),the positive predictive value was 96.20%(228/237),the negative predictive value was 100.00%(159/159),the accuracy was 97.73%(387/396),and the consistency with the postoperative pathological diagnosis was 0.937.Conclusion The ultrasound multimodal diagnostic mode and ultrasonic precision interventional technology can be used in differentiating the benign from malignant solid breast masses with high diagnostic accuracy.

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