ObjectiveTo investigate the effects of Shengui Jiangtang Formula on insulin resistance and glucose-lipid metabolism in spontaneous type 2 diabetic db/db mice based on the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead box protein O1 （FoxO1） signaling pathway， and to provide theoretical foundation for its clinical application through fundamental experiments. MethodsA randomized controlled design was employed in this study. Thirty spontaneous type 2 diabetic db/db mice meeting the inclusion criteria （fasting blood glucose >7.0 mmol·L^-1 and random blood glucose on a different day≥11.1 mmol·L^-1） were selected as the subjects. After stratified block randomization by body weight and blood glucose levels， they were randomly assigned to a model group， a metformin group， and a Shengui Jiangtang formula group， with n=10 per group. Ten db/m mice were used as the normal group. During the 5-week intervention， general indicators （including general condition， fasting blood glucose （FBG）， body weight， and food intake） were recorded weekly. An oral glucose tolerance test （OGTT） was performed at week 5. After 5 weeks， serum was collected to measure glucose-lipid metabolism parameters. Liver tissues were analyzed as follows： Histopathology was observed through hematoxylin and eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Oil red O staining. The expression of proteins and genes related to the PI3K/Akt/FoxO1 signaling pathway was quantitatively analyzed using Western blotting （Western blot） and real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsGeneral observations： The mice in the normal group were generally healthy， exhibited agile responses and had smooth and glossy fur. Compared with the normal group， the mice in the model group displayed typical symptoms of polydipsia， polyphagia， and polyuria， along with listlessness and rough fur. Their food intake， initial body weight， liver weight， and liver index were all significantly higher than those in the normal group （P<0.01）. After 5 weeks of drug intervention， neither the Shengui Jiangtang Formula group nor the metformin group significantly affected the food intake of the model mice. Compared with the model group， no statistically significant difference was observed in liver weight or liver index in the Shengui Jiangtang formula group. Serum biochemical indicators： Compared with the normal group， the model group showed significantly elevated levels of FBG， fasting insulin， homeostatic model assessment of insulin resistance （HOMA-IR）， glycosylated serum protein， and blood lipids. After drug intervention， compared with the model group， the Shengui Jiangtang formula group significantly reduced FBG in the model mice （P<0.01）. The blood glucose levels at all time points during the OGTT in the Shengui Jiangtang Formula group were lower than those in the model group， with statistically significant differences in the 0 min blood glucose and the area under the curve for glucose compared to the model group （P<0.05）. Furthermore， the formula significantly reduced fasting insulin levels， HOMA-IR， and glycosylated serum protein levels （P<0.05）. It also showed a tendency to decrease blood lipids， liver enzymes （aspartate aminotransferase， alanine aminotransferase）， and blood urea nitrogen levels， and a tendency to increase creatinine levels， although these differences were not statistically significant. Liver histomorphology： HE staining indicated that Shengui Jiangtang formula improved the morphological structure of hepatocytes and attenuated steatosis in diabetic mice. Liver PAS staining showed that it increased hepatic glycogen content and promoted hepatic glycogen synthesis in diabetic mice. Oil red O staining demonstrated that it reduced lipid deposition within hepatocytes. Western blot： Compared with the normal group， the model group showed decreased protein expression of PI3K， Akt， p-Akt， and p-FoxO1， and increased FoxO1 protein expression. Compared with the model group， both the metformin and Shengui Jiangtang Formula groups showed increased protein expression of PI3K， Akt， p-Akt， and p-FoxO1， and decreased FoxO1 protein expression. Real-time PCR： Compared with the normal group， the mRNA expression of PI3K and Akt was downregulated （P<0.05）， and the mRNA expression of FoxO1 was downregulated （P<0.05） in the model group. ConclusionShengui Jiangtang Formula can improve insulin resistance and glucose-lipid metabolic disorders in db/db mice. It alleviates hepatic steatosis， promotes hepatic glycogen synthesis， and reduces lipid deposition in these mice. The mechanism by which Shengui Jiangtang Formula improves insulin resistance may be associated with the PI3K/Akt/FoxO1 signaling pathway.

Diabetic retinopathy （DR） is a microvascular complication of diabetes and one of its most common complications. Prolonged hyperglycemia induces oxidative stress， inflammatory responses， apoptosis， and pathological angiogenesis， ultimately disrupting the blood-retinal barrier（BRB） and leading to visual impairment or even blindness. Recent studies show that the nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway plays an important role in the development of DR's pathological changes. Meanwhile， Chinese herbal monomers have been shown to modulate the Nrf2 signaling pathway， thereby intervening in the development of DR. In terms of inhibiting oxidative stress， saponin compounds such as platycodin-D and ginsenoside Rb1 downregulate the expression of malondialdehyde （MDA）， thereby ameliorating retinal oxidative stress. Flavonoids such as total flavonoids from Pueraria lobata flower and puerarin upregulate the expression of superoxide dismutase （SOD） and glutathione peroxidase （GPx）， effectively clearing lipid peroxides. Regarding the suppression of inflammation， phenolic compounds like resveratrol and chlorogenic acid inhibit the nuclear factor kappa B （NF-κB） pathway， reducing the release of tumor necrosis factor-alpha （TNF-α） and mitigating inflammatory responses. In the context of inhibiting apoptosis， polysaccharides such as Polygonatum sibiricum polysaccharide and Angelica sinensis polysaccharide downregulate the expression of the pro-apoptotic protein Bcl-2-associated X protein （Bax） and suppress the activity of the executioner Caspase-3， thereby reducing the apoptosis rate. As for the inhibition of neovascularization， compounds including bilobalide and physcion significantly decrease the protein expression of vascular endothelial growth factor （VEGF）， leading to a reduction in retinal pathological angiogenesis. Furthermore， Chinese herbal compound prescriptions such as Tongluo Zhujing pills， Yiqi Huoxue Yangyin decoction， Qiming granules， and Danlou tablets can also intervene in the onset and progression of DR through the mechanisms described above. In summary， both Chinese herbal monomers and Chinese herbal compound prescriptions can modulate the Nrf2 signaling pathway to inhibit oxidative stress， alleviate inflammation， and participate in maintaining BRB integrity， suppressing retinal neovascularization， and preventing neurodegeneration， thereby delaying the progression of DR. Therefore， this paper reviews and summarizes recent studies at home and abroad on how traditional Chinese medicine （TCM） works to treat DR， and the relationship between the Nrf2 pathway and DR. It aims to provide research ideas for preventing and treating DR.

OBJECTIVE To provide references for the accurate identification and management of immune-related cutaneous adverse events （irCAEs） caused by durvalumab， and ensuring safe clinical drug use. METHODS Clinical pharmacists participated in the diagnosis and treatment process of a patient with gallbladder cancer who developed irCAEs caused by durvalumab. The clinical pharmacists systematically reviewed the patient’s past medical history and medication history， and assisted physicians in assessing the association between adverse drug reactions and administered drugs. Meanwhile， the clinical pharmacists conducted a graded assessment of the adverse reaction， proposed recommendations such as discontinuing durvalumab and adjusting the administration regimen of glucocorticoids， assisted physicians in restarting immunotherapy， and carried out medication education and other pharmaceutical care. RESULTS The occurrence of irCAEs in this patient was “highly likely” related to durvalumab and was classified as severe. The physicians adopted the clinical pharmacist’s opinion， and after symptomatic treatment， the patient’s skin symptoms improved， and discharged with medication. After the completion of glucocorticoid therapy for the patient， the physician restarted immunotherapy with tislelizumab， and no related adverse reactions occurred again in the patient. CONCLUSIONS Durvalumab can cause irCAEs such as severe skin maculopapular rash. In clinical practice， it is crucial to promptly identify and discontinue suspicious drugs， immediately implement effective symptomatic treatment measures， and actively resume immunotherapy to ensure the continuity and safety of the patient’s treatment.

ObjectiveTo observe the effect of functional pelvic floor muscle training on pelvic floor muscle function, incontinence symptoms and quality of life in female patients with stress urinary incontinence (SUI). MethodsFrom February, 2024 to July, 2025, 40 female patients with SUI were recruited from Beijing Bo'ai Hospital and advertisements. They were randomly divided into control group (n = 20) and experimental group (n = 20). The control group received conventional pelvic floor muscle contraction and relaxation training, and the experimental group received functional pelvic floor muscle contraction and relaxation training, for eight weeks. The data of pelvic floor muscle strength, pelvic floor muscle surface electromyography (sEMG), 1-hour urine pad test and Incontinence Quality of Life questionnaire (I-QOL) were collected before and after training. The compliance rate was counted after training. ResultsOne case dropped down in the control group and three cases dropped down in the experimental group. After treatment, the pelvic floor muscle strength increased in both groups (|Z| > 3.317, P < 0.01), the pre-resting average value, sustained contraction average value and durable contraction average value of sEMG improved in the control group (|t| > 2.731, P < 0.05), the mass of 1-hour urine pad significantly reduced (t > 9.215, P < 0.001) and the I-QOL score significantly increased (|t| > 13.229, P < 0.001) in both groups; compared with the control group, the pelvic floor muscle strength significantly increased (Z = -2.281, P = 0.023), the mass of 1-hour urine pad significantly reduced (t = 4.215, P < 0.001), the I-QOL score significantly increased (t = -4.501, P < 0.001), and the compliance rate significantly increased (Z = -2.798, P < 0.01) in the experimental group . ConclusionFunctional pelvic floor muscle training can significantly improve pelvic floor muscle strength, incontinence symptoms and quality of life in female patients with SUI.

Objective: To investigate the incidence and independent risk factors of adverse events (AEs) associated with therapeutic plasma exchange (TPE) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to provide evidence to support the safe use of TPE in clinical practice. Methods: This retrospective study included 167 allo-HSCT recipients who underwent a total of 385 TPE procedures between March 2022 and December 2023. Patients were divided into two groups according to the occurrence of TPE-related AEs. Baseline characteristics, plasma exchange parameters, and clinical features were collected. Univariate analysis and multivariable Firth logistic regression were performed to identify independent risk factors for AEs. Results: A total of 385 TPE procedures were performed in 167 allo-HSCT patients, and 33 patients (19.8%) experienced TPE-related AEs. Among the 33 patients who experienced AEs, allergic reactions were the most common (n=18, 54.5%), followed by blood pressure fluctuations (n=11, 33.3%) and hypocalcemia (n=4, 12.1%). Most AEs were classified as grade II (n=23, 69.7%), and no grade IV (fatal) events were observed. Univariate analysis demonstrated a significant difference in the incidence of AEs among different hematocrit (HCT) categories (<20%, 20%-30%, and>30%) (Fisher's exact test, P=0.022). Although the overall difference was statistically significant, none of the pairwise comparisons remained significant after Bonferroni correction (adjusted P>0.0167). Multivariable Firth logistic regression identified higher HCT levels, analyzed as a continuous variable (OR=1.07, 95% CI: 1.01-1.13, P=0.020), and TPE performed for cytokine release syndrome (CRS) (OR=9.21, 95% CI: 1.25-78.00, P=0.030) as potential independent risk factors for TPE-related AEs. Receiver operating characteristic (ROC) curve analysis showed that HCT had an AUC of 0.67 (95% CI: 0.57-0.77) for predicting AEs, with an optimal cutoff value of 24.5%, a sensitivity of 60.6%, and a specificity of 75.4%. Using this cutoff, the AEs rate was significantly higher in patients with HCT≥24.5% than in those with HCT<24.5% (37.7% vs 11.4%, P<0.001). Conclusion: A-mong allo-HSCT patients receiving TPE, allergic reactions were the predominant AEs. Higher HCT levels and TPE performed for CRS may be associated with an increased risk of AEs. HCT≥24.5% may help identify patients requiring intensified monitoring, although its discriminatory ability is moderate (AUC=0.67) and it should not be used as a standalone criterion for clinical decision-making. Findings regarding the CRS subgroup require validation in larger cohorts. Optimizing extracorporeal circuit priming and strengthening peri-procedural monitoring may help improve the safety of TPE.

Objective The aim of this study was to analyze the incidence and mortality of esophageal cancer and its trend in Lianyungang city from 2008 to 2019.Methods The data of esophageal cancer in all cancer registry areas in Lianyungang city were col-lected and sorted out,and the quality control reached the standards.The incidence,mortality,age-standardized rate of Chinese population(ASRC),age-standardized rate of World population(ASRW),cumulative rate at 0-74 years old,truncation rate of 35-64 years old,and composition ranking were calculated.The Joinpoint4.7.0.0software was used to analyze the average annual percentage change(AAPC)of the age-standardized incidence and mortality of esophageal cancer by the standard population(ASIRC and ASMRC).Results From 2008 to 2019,the incidence of esophageal cancer in Lianyungang city was 25.90/100,000,ASIRC was 17.95/100,000,ASIRW was 17.91/100,000,ranking the third in the incidence spectrum of malignant tumors.The mortality was 20.55/100,000,ASMRC was 13.86/100,000,and ASMRW was 13.71/100,000,ranking the third in the malignant tumor mortality spectrum.The incidence,mortali-ty,ASIRC and ASMRC of esophageal cancer were higher in men than those in women,and higher in rural areas than those in urban are-as.From 2008 to 2019,the change trend of incidence and mortality of esophageal cancer in Lianyungang city was the same,showing a downward trend.The AAPC of the ASIRC was-6.19%(95%CI:-7.08%-5.30%,P<0.001),and the AAPC of the ASMRC was-4.03%(95%CI:-5.81%-2.22%,P<0.001).Among them,the ASIRC and ASMRC of esophageal cancer in urban and rural areas showed a downward trend(P<0.05).Among them,the ASIRC and ASMRC of esophageal cancer in urban women decreased the most,with an average annual decline of-7.99%(95%CI:-10.86%-5.03%,P<0.001)and-9.19%(95%CI:-12.35%-5.93%,P<0.001).Conclusion The incidence and mortality of esophageal cancer in Lianyungang city have shown a downward trend,a rural areas and male populations are the key prevention and control populations for esophageal cancer.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of ileocecal valve lipoma.Methods:A retrospective cohort study was performed on data of ileocecal lipoma patients who underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2013 to June 2023. According to the lesion location, the patients were divided into ileocecal valve group and cecum group. The operation time, operation speed, en bloc resection rate, complications, and follow-up outcomes between the two groups were compared.Results:A total of 59 patients with ileocecal lipoma were enrolled, including 31 patients in the ileocecal valve group and 28 patients in the cecum group.There were no significant differences in gender, age, specimen size, or lesion size between the two groups ( P>0.05). Lipomas in both the ileocecal valve group and the cecum group were successfully resected by ESD. The en bloc resection rates were 100.0% (31/31) and 92.9% (26/28) respectively, and the difference was not statistically significant ( χ2=0.033, P=0.133). Median operative duration significantly differed between the two groups ( ileocecal valve group 26 min VS cecum group 20 min, Z=-0.136, P=0.027), as did resection speed (ileocecal valve group 0.14 cm2/min VS cecum group 0.24 cm2/min, Z=-0.223, P=0.022). Adverse events included one postoperative fever in the ileocecal valve group and one delayed bleeding in the cecum group. During the median follow-up of 38 months (7-106 months), there was no case of residual tumor or recurrence. Conclusion:Despite technical challenges in ESD of ileocecal valve lipoma, it is still a safe, feasible and effective treatment method.

ObjectiveTo evaluate the effects of Wuhua herbal tea on chronic unpredictable mild stress (CUMS)-induced depression and explore its mechanism of action in combating depression.MethodsWe tested the antidepressant effects of Wuhua herbal tea in a rat model of CUMS-induced depression using fluoxetine as a positive control. The rats were divided into four groups: control group, model group, fluoxetine group, and Wuhua herbal tea group. The rats underwent body weight measurements, sucrose preference test, and open-field test. Enzyme-linked immunosorbent assay kits were used to detect the serum levels of serotonin, dopamine, adrenocorticotropic hormone (ACTH), corticosterone, norepinephrine, and interleukin-6. Intergroup comparisons and detection of brain-derived neurotrophic factor (BDNF), cAMP-response element binding protein (CREB), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) mRNA expression in the hippocampus were performed using RT-PCR. Immunohistochemistry was used to identify the expression of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) proteins in hippocampal paraffin sections of CUMS rats.ResultsCompared with the control group, the model group rats had depressive tendencies, exhibiting low vitality and interest in various behavioral indicators which were signs of despair. The Wuhua herbal tea group statistically increased the levels of serotonin and dopamine in the serum of CUMS rats to varying degrees (P = .015 and P = .002); reduced serum levels of ACTH, corticosterone, norepinephrine, and interleukin-6 (all P .05); and decreased mRNA expression of BDNF, CREB, JAK2, and STAT3 in the hippocampus (all P .05); and decreased p-STAT3 protein levels (P = .006).ConclusionWuhua herbal tea shows antidepressant potential in CUMS rats by modulating the HPA axis and inhibiting JAK2-STAT3 overactivation, alleviating neuroinflammation. It also restores BDNF-CREB pathway function, reducing depressive symptoms.

Gentiopicroside(GPS)is the main active ingredient extracted from Gentiaceae.It has anti-inflammatory,antioxidant,analgesic,anti-fibrosis,inhibition of tumor cell proliferation and improvement of glucose and lipid metabolism.Gentiaceae shows a wide range of application prospects in the treatment of diabetes,liver diseases,bone and joint diseases and other diseases.This paper reviewed the pharmacokinetics of gentiopicrin,including its pharmacokinetic properties in different animal models,and its mechanism and targets in the treatment of diabetes mellitus and its complications,liver injury,bone and joint diseases.Studies have shown that gentiopictin exerts its therapeutic effects by regulating various signaling pathways,such as PI3K/AKT,FOXO1,PPAR-γ,NF-κB,etc.Although the current research has made some progress,there are still limitations,such as most studies focused on animal models and in vitro experiments,lack of high-quality clinical evidence-based trials support.Future studies should further explore the new targets and signal transduction pathways of gentiopicroside,improve its bioavailability,and strengthen the research of traditional Chinese medicine compounds,so as to give full play to the advantages of holistic treatment of traditional Chinese medicine.

AIM:Fine particulate matter(PM2.5)is closely associated with airway hyper-responsiveness(AHR).However,the underlying mechanism by which PM2.5 leads to AHR is still unclear.This study aimed to investi-gate the respiratory effects of ambient PM2.5 exposure.METHODS:Forty mice were randomly divided into five groups:control group(intranasal saline),lipopolysaccharide(LPS)group(100 mg/L),PM2.5 low-dose group(0.003 5 mg/d),PM2.5 medium-dose group(0.007 mg/d),and PM2.5 high-dose group(0.014 mg/d).They were treated with intranasal in-stillation for 30 d.Lung function and tracheal contractile responses were evaluated using whole-body plethysmography and sensitive wire myograph.Inflammatory mediators in serum and oxidative stress parameters were detected using enzyme-linked immunosorbent assay(ELISA).Lung tissues were subjected to HE and Masson staining.RT-qPCR and Western blot were used to determine the expression of contractile receptors and the phosphorylation of the mitogen-activated protein kinase(MAPK)signal pathway.RESULTS:Intranasal instillation of PM2.5 significantly increased airway resistance in mice and enhanced tracheal contractility in response to carbachol.PM2.5 elevated levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in serum.PM2.5 instillation also led to a decrease in glutathione peroxidase(GSH-Px)levels and an increase in malondialdehyde(MDA)levels.Lung tissue exhibited notable pathological changes,including inflammatory cell infiltration,hyperplasia of alveolar epithelial cells,and collagen deposition.Mechanistically,exposure to PM2.5 increased the expression of muscarinic M3 receptor mRNA and protein,as well as the phosphorylation of p-ERK1/2 and p-p38 proteins following PM2.5 instillation.CONCLUSION:Intranasal instillation of PM2.5 induced inflammation and oxidative stress,along with the activation of the extracellular signal-regulated kinase 1/2(ERK1/2)and p38 MAPK pathways,resulting in the upregulation of M3 receptor-induced AHR.