1.Effect of Shengui Jiangtang Formula on Glucose and Lipid Metabolism in Type 2 Diabetic db/db Mice via PI3K/Akt/FoxO1 Signaling Pathway and Underlying Mechanisms
Zairan WANG ; Yifei ZHU ; Jiahe TANG ; Lingling QIN ; Lili WU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):42-51
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.
2.Research Progress of Traditional Chinese Medicine in Improving Diabetic Retinopathy Based on Nrf2 Signaling Pathway
Xueqing LIU ; Xinyu ZHONG ; Tingting WANG ; Ning WANG ; Man LIU ; Li WU ; Lili WU ; Lingling QIN ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):69-78
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.
3.Pharmaceutical care for a case of severe dermal toxicity induced by durvalumab
Liulian JI ; Zhengbi QIN ; Pengcheng LIU ; Xiaowen DENG ; Lili LIU ; Lijuan YAO ; Tingting LIU ; Pingchen GU
China Pharmacy 2026;37(1):88-91
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.
4.Effect of functional pelvic floor muscle training on stress urinary incontinence in women
Ya'nan LI ; Miao YE ; Juan WU ; Cong CHEN ; Lingfang WAN ; Lili YU ; Linlin GAO ; Yi QIN ; Huafang JING
Chinese Journal of Rehabilitation Theory and Practice 2026;32(6):690-698
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.
5.Risk factors for therapeutic plasma exchange-related adverse events in patients undergoing allogeneic hematopoietic stem cell transplantation
Jingyuan QIN ; Jing LONG ; Lili YUAN ; Yuemei ZHANG ; Jiali QIAO ; Xuelian YANG ; Qingxue YIN ; Juan CHEN
Chinese Journal of Blood Transfusion 2026;39(9):1254-1261
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.
6.Mortality trend and prediction of chronic respiratory disease in Lianyungang City from 2011 to 2029
ZHONG Wei ; LI Weiwei ; XIANG Lu ; CHAI Lili ; DONG Jianmei ; MA Zhaojun ; QIN Xucheng ; ZHANG Weiwei
Journal of Preventive Medicine 2026;38(2):181-186
Objective:
To analyze the mortality trend of chronic respiratory diseases in Lianyungang City, Jiangsu Province from 2011 to 2024, and predict the mortality from 2025 to 2029, so as to provide the evidence for developing forward-looking prevention and control strategies and targeted intervention measures.
Methods:
Chronic respiratory disease death surveillance data in Lianyungang City from 2011 to 2024 were collected through the Jiangsu Chronic Disease Management Information Platform. The crude mortality was calculated and standardized using the data of the Sixth National Population Census in 2010. Average annual percent change (AAPC) was used to analyze the mortality trends of chronic respiratory diseases by gender, region, and age in Lianyungang City from 2011 to 2024. The GM (1,1) grey model was established using the crude mortality of chronic respiratory diseases from 2011 to 2024 to predict the crude mortality of chronic respiratory diseases from 2025 to 2029.
Results:
From 2011 to 2024, the crude mortality and standardized mortality of chronic respiratory diseases in Lianyungang City were 52.20/105 and 36.57/105, respectively. The crude mortality and standardized mortality were 53.14/105 and 43.79/105 in males, respectively, which were higher than 51.17/105 and 30.14/105 in females (both P<0.05). The crude mortality and standardized mortality were 55.62/105 and 39.85/105 in rural areas, respectively, which were higher than 38.11/105 and 24.15/105 in urban areas (both P<0.05). From 2011 to 2024, the standardized mortality of chronic respiratory diseases showed downward trends in the total population, males, females, urban areas, and rural areas (AAPC=-6.956%, -5.175%, -8.659%, -4.290%, and -7.369%, all P<0.05). The crude mortality of chronic respiratory diseases in the total population showed an upward trend with increasing age (P<0.05), reaching a peak of 1 371.20/105 in the ≥80 years group. The top two causes of chronic respiratory disease deaths were chronic obstructive pulmonary disease and bronchial asthma, with 31 792 cases and 3 254 cases, accounting for 82.40% and 8.43%, respectively. The GM (1,1) grey model prediction results showed that the crude mortality of chronic respiratory diseases in the total population from 2025 to 2029 would be 37.91/105, 36.32/105, 34.80/105, 33.34/105, and 31.95/105, respectively (average relative error=8.76%).
Conclusions
From 2011 to 2024, the mortality of chronic respiratory diseases in Lianyungang City showed a downward trend. The risk of death from chronic respiratory diseases was higher in males, rural areas, and the elderly. It is predicted that the mortality of chronic respiratory diseases will decrease year by year from 2025 to 2029.
7.Antidepressant effects and mechanisms of Wuhua herbal tea in a rat model of chronic unpredictable mild stress
Zhiwei Qi ; Lingling Qin ; Ming Gao ; Ruifeng Yang ; Congyi Liu ; Ning Wang ; Wenjing Li ; Yongxin Huang ; Lili Wu ; Tonghua Liu
Journal of Traditional Chinese Medical Sciences 2025;2025(3):364-374
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.
8.Combination of Astragalus-Salvia and Ophiopogon-Dendrobium herb pairs alleviates Sjögren's Syndrome via inhibiting the JAK1/STAT3 and PI3K/AKT pathways in NOD/Ltj mice.
Peng SUN ; Lili ZHU ; Yang YU ; Sijing HU ; Mengyi SHAN ; Xuan ZHAO ; Xinchang WANG ; Qiaoyan ZHANG ; Luping QIN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(6):733-741
Sjögren's syndrome (SS) is an autoimmune disease characterized primarily by oral and periocular dryness. Astragalus-Salvia (AS) and Ophiopogon-Dendrobium (OD) represent two frequently utilized herb pairs in SS treatment. While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms, its underlying mechanism remains unclear. This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic (NOD)/Ltj mice with SS. The study utilized NOD/Ltj mice as SS models, administering AS-OD treatment for 10 weeks at doses of 113.1, 226.2, and 339.3 mg·d-1·20 g-1. Results demonstrated that AS-OD improved SS symptoms, evidenced by enhanced salivary flow rate, decreased anti-SSA/Ro and anti-SSB/La antibody levels, increased swimming duration, and reduced lactate (LA) and blood urea nitrogen (BUN) levels in NOD/Ltj mice. AS-OD reduced lymphocyte infiltration, enhanced Aquaporin-5 (AQP5) expression in the submandibular gland, decreased inflammatory cytokine levels in the submandibular gland, and reduced the T helper type 17/regulatory T lymphocyte (Th17/Treg) cell ratio in the spleen. Transcriptomic and proteomic analyses indicated AS-OD's involvement in regulating phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and Janus kinase 3/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways, with inhibitory effects validated in both NOD/Ltj mice submandibular gland and A-253 cells. Furthermore, AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway. In A-253 cells, AS-OD reduced inflammatory cytokine levels, CXC chemokine ligand 9/10 (CXCL9/10), and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway. AS-OD mitigates SS by suppressing inflammation and immune responses through the PI3K/AKT and JAK1/STAT3 pathways.
Animals
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STAT3 Transcription Factor/genetics*
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Sjogren's Syndrome/immunology*
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Mice, Inbred NOD
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Proto-Oncogene Proteins c-akt/genetics*
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Phosphatidylinositol 3-Kinases/genetics*
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Mice
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Drugs, Chinese Herbal/administration & dosage*
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Signal Transduction/drug effects*
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Janus Kinase 1/genetics*
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Humans
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Female
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Astragalus Plant/chemistry*
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Male
9.Analysis of the incidence and mortality of esophageal cancer and its trend in Lianyungang city from 2008 to 2019
Lili CHAI ; Weiwei LI ; Jianmei DONG ; Xucheng QIN ; Weiwei ZHANG ; Lu XIANG ; Wei ZHONG ; Wei WANG ; Zhaojun MA
Practical Oncology Journal 2025;39(2):80-85
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.
10.Mechanistic study on the male flower of Eucommia ulmoides-Sanchi flower herb pair for improving glucose and lipid metabolism in type 2 diabetes mellitus model mice
Ning WANG ; Congyi LIU ; Ying DING ; Xinyu ZHONG ; Zimeng HUANG ; Na ZHENG ; Qiu'e ZHANG ; Ruifeng YANG ; Lili WU ; Lingling QIN ; Tonghua LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1390-1403
Objective Based on the traditional Chinese medicine theory of"simultaneous regulation of the liver and kidney,"this study integrated network pharmacology prediction,molecular docking,and animal experimental validation to analyze the multi-target regulatory network of Duzhong Xionghua(the male flower of Eucommia ulmoides)-Sanqi Hua(Sanchi flower)herb pair(hereinafter called"herb pair")in modulating glucolipid metabolic disorders in type 2 diabetes mellitus(T2DM),thereby elucidating its underlying molecular mechanism.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,China National Knowledge Infrastructure,VIP Database for Chinese Technical Periodicals,and Wanfang Data were used to obtain the active ingredients of the male flower of Eucommia ulmoides and Sanchi flower.PubChem Compound,SwissTargetPrediction,and SuperPred were used to screen and predict the targets of the drugs;The Human Gene Database,The Online Mendelian Inheritance in Man,and Therapeutic Target Database were used to screen the key gene targets of T2DM.A"component-target-pathway"network diagram was constructed using Cytoscape software,and Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were employed to identify the functions of the relevant target genes and pathways.Molecular docking was used to verify the binding activities of the core components and the key targets.For animal experiments,spontaneous T2DM model mice were used,in which the normal group consisted of six mice(wild type)from the same litter,and the 24 successfully modeled mice were randomly divided into model,metformin(0.26 g/kg),high-dose herb pair(2.6 g/kg),and low-dose herb pair groups(1.3 g/kg)according to the blood glucose levels and body weights,with six mice per group.The drugs were administered by gavage daily for six consecutive weeks.The body weight and fasting blood glucose(FBG)levels were measured weekly,and an oral glucose tolerance test was performed in the fifth week.At the end of drug administration,body weight,naso-anal length,liver and bilateral epididymal adipose mass were measured;pathological changes in the liver were observed using HE staining;serum levels of aspartate transaminase(AST),alanine amino-transferase(ALT),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected using colorimetric assay;and liver tissue phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase-3β(GSK-3β)signaling pathway protein expressions were determined using Western blotting.Results Network pharmacology screening identified 38 active components and 669 potential targets of the herb pair.Intersection analysis with 1,275 T2DM-related targets yielded 185 common targets.Protein-protein interaction network analysis and pathway enrichment revealed the PI3K/AKT signaling pathway as a key mechanism.Molecular docking confirmed the strong binding affinity of the core components to key targets such as AKT1,suggesting that the herb pair may activate the PI3K/AKT pathway and inhibit GSK-3β activity via beta-sitosterol etc.Animal experiments demonstrated that,compared with the model group,the metformin group exhibited reduced FBG,AST,and ALT levels(P<0.01),but failed to improve body weight,Lee's index,or epididymal fat coefficient.Both herb pair doses significantly lowered Lee's index,hepatic index,and the epididymal fat coefficient(P<0.01),with the low-dose herb pair group showing attenuated body weight gain in mice.In contrast,the high-dose herb pair group exhibited decreased FBG,improved glucose tolerance,reduced TC,TG,and LDL-C levels,and increased HDL-C level(all P<0.01).HE staining revealed that all metformin and the herb pair markedly restored hepatic structure and alleviated steatosis in model mice,with more pronounced effects in the high-dose group than in the low-dose group.Western blotting result indicated that in the low-dose herb pair group,phospho-PI3K(p-PI3K),AKT,and phospho-GSK-3β(p-GSK-3β)protein expressions significantly increased(P<0.05 or P<0.01),whereas GSK-3β decreased(P<0.05).The high-dose group exhibited enhanced PI3K,p-PI3K,AKT,phospho-AKT,and p-GSK-3β protein expressions(all P<0.01),accompanied by reduced GSK-3β expression(P<0.01).Conclusion The male flower of Eucommia ulmoides-Sanchi flower herb pair may ameliorate T2DM-related glucolipid metabolic disorders by modulating the PI3K/AKT/GSK-3β pathway.


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