1.Expert consensus on the clinical application of domestic ultra-high-definition medical endoscopes in cardiovascular surgery (2026 edition)
Junfei ZHAO ; Biaochuan HE ; Yun TENG ; Xiaohua LI ; Zerui CHEN ; Chungeng LIU ; Yijiu REN ; Chang CHEN ; Nianguo DONG ; Jimei CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(06):857-865
This consensus focuses on the clinical application of domestic ultra-high-definition (UHD) medical endoscopes in cardiovascular surgery, addressing their clinical value, key technical aspects, and strategies for broader implementation. It traces the evolution of domestic endoscopic platforms from high-resolution imaging toward integrated advanced functionalities such as fluorescence imaging, three-dimensional visualization, and intelligent assistance. The document outlines standardized procedural steps and perioperative management pathways for minimally invasive endoscopic cardiovascular surgery and summarizes specific application scenarios and technical considerations in congenital heart disease, valvular disorders, coronary artery disease, arrhythmias, and cardiac tumors. Furthermore, recommendations are provided regarding professional training, multicenter collaboration, the establishment of clinical evaluation systems, and coordinated policy-industry support to promote standardized adoption and high-quality dissemination of domestic medical devices. Based on available evidence and expert agreement, 16 consensus statements are presented, aiming to offer authoritative and actionable guidance for clinical practice.
2.Meta-analysis of the safety and efficacy of transurethral blue laser vaporization of the prostate,transurethral resection of the prostate or plasmakinetic resection of the prostate in the treatment of benign prostatic hyperplasia
Zhongchao HUO ; Haifeng CHENG ; Yongzhi HE ; Lei WANG ; Rui DING ; Jianqi YANG ; Wenting ZHAO ; Zi CAI ; Caiying KONG ; Yiping GAO
Journal of Modern Urology 2026;31(2):140-146
Objective To compare the efficacy and safety of transurethral blue laser vaporization of the prostate, transurethral resection of the prostate (TURP) or plasmakinetic resection of the prostate in the treatment of benign prostatic hyperplasia (BPH). Methods The domestic and foreign clinical studies on transurethral blue laser vaporization of the prostate (observation group), TURP or plasmakinetic resection of the prostate (control group) in the treatment of BPH during Jan. 2015 and Mar. 2025 were retrieved. The data were extracted with Cochrane systematic review method. The operation time, decrease in hemoglobin, bladder irrigation time, catheter indwelling time, total complication rate, retrograde ejaculation rate and urinary incontinence rate of the two groups were compared with RevMan 5.3.0 statistical software. Results A total of 5 Chinese studies involving 491 patients (248 in the observation group and 243 in the control group) were included in the Meta-analysis. Compared with the control group, the observation group had shorter operation time [MD=-20.80, 95%CI:-26.88—-14.72, P<0.00001], less decrease in hemoglobin [MD=-10.61, 95%CI: -20.21—-1.01, P=0.03], shorter bladder irrigation time [MD=-17.85, 95%CI: -32.62—-3.09, P=0.002], shorter catheter indwelling time [MD=-1.71, 95%CI: -2.81—- 0.62, P=0.002], lower total complication rate [OR=0.11, 95%CI: 0.06—0.21, P<0.00001], lower retrograde ejaculation rate [OR=0.05, 95%CI: 0.02—0.16, P<0.00001] and lower urinary incontinence rate [OR=0.24, 95%CI: 0.07—0.79, P=0.02]. There were no significant differences in other complications between the two groups (P>0.05). The international erectile function score (IIEF-5) of the observation group was significantly higher than that of the control group [MD=1.87, 95%CI:1.16—2.57, P<0.00001]. There were no significant differences in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax) and post-voiding residual (PVR) between the two groups (P>0.05). Conclusion All three surgical procedures can effectively improve the lower urinary tract symptoms of BPH patients. Compared with TURP or plasmakinetic resection of the prostate, transurethral blue laser vaporization of the prostate has obvious advantages in terms of perioperative recovery, reduction of total complications, urinary incontinence and retrograde ejaculation rates, and preservation of sexual function.
3.Live attenuated measles, mumps and rubella vaccine induces immunogenic cell death to activate anti-tumor immunity in triple-negative breast cancer
JIANG Lina1a ; WANG Hao2 ; WEI Hong1b ; ZHAO Qian1a ; HE Jun1a ; CHI Qianwen1b ; WEI Yilin1c ; HE Yanran1d ; FU Pengcheng1d
Chinese Journal of Cancer Biotherapy 2026;33(6):641-650
[摘 要] 目的:探讨麻疹-流行性腮腺炎-风疹联合减毒活疫苗(MMR)通过诱导免疫原性细胞死亡(ICD)对三阴性乳腺癌(TNBC)的免疫调节机制。方法:体外实验采用CCK-8法检测MMR对TNBC细胞4T1和MDA-MB-231存活率的影响,免疫荧光法检测MDA-MB-231细胞中钙网蛋白(CALR)表达,磷钼酸比色法检测MDA-MB-231细胞内ATP的含量,ELISA检测细胞上清液中高迁移率族蛋白B1(HMGB1)的表达水平,通过GEPIA网站分析CALR和HMGB1对乳腺癌患者生存期的影响。体内实验中经皮下注射4T1-Luc细胞于雌性BALB/c小鼠乳腺脂肪垫构建TNBC小鼠模型。设Control组、盐酸阿霉素(Dox)组、MMR组,按照分组每两天静脉给药1次,连续给药3次。动物活体成像系统观察肿瘤体积变化;记录小鼠体质量及各器官指数初步评估疫苗安全性;H-E染色观察肿瘤病理变化;免疫组化和Western blotting检测肿瘤中CALR和HMGB1蛋白的表达。流式细胞术分析小鼠脾T淋巴细胞亚群及肿瘤树突状细胞和巨噬细胞比例;免疫组化检测肿瘤CD8+ T淋巴细胞浸润;ELISA检测血清中促炎细胞因子IL-6和TNF-α含量。结果:MMR对4T1细胞的活性抑制作用较弱;MMR对MDA-MB-231细胞抑制率达90.39%(P < 0.001)。与Control组相比,MMR组MDA-MB-231细胞中ICD相关蛋白(CALR、ATP、HMGB1)表达上调(P < 0.001)。GEPIA网站分析表明,CALR和HMGB1高表达的患者总生存期有所延长。MMR延缓了荷瘤小鼠肿瘤体积增长(P < 0.001),延长小鼠的生存期,且28 d内MMR组荷瘤小鼠体重与Control组无显著性差异(P > 0.05);H-E染色显示,与Control组相比,MMR组小鼠肿瘤组织坏死区域扩大且有免疫细胞浸润;MMR上调肿瘤ICD相关蛋白CALR、HMGB1的表达水平;MMR组脾CD4+、CD8+ T淋巴细胞及肿瘤树突状细胞和M1型巨噬细胞的比例增加(P < 0.05),CD8+ T淋巴细胞在肿瘤组织中的浸润增加(P < 0.001),且促炎细胞因子IL-6和TNF-α水平升高(P < 0.01)。结论:MMR减毒活疫苗对TNBC的抗肿瘤作用可能与诱导肿瘤发生ICD进而激活抗肿瘤免疫相关。
4.The hypolipidemic function and hepatic protective effects of Xuetong capsules
Lin HE ; Yanqiong CHENG ; Juanjuan ZHAO ; Huilan LU ; Jun YANG ; Fangjian CHEN
Journal of Pharmaceutical Practice and Service 2026;44(6):289-295
Objective To investigate the effects of Xuetong capsule on blood lipids and liver lesion in hyperlipidemic model animals. Methods Sixty ICR mice were randomly divided into six groups. The normal control group was fed with normal diet, the other groups were fed with high-fat diet to induce hyperlipidemia. After four weeks feeding, the three groups were given low, middle, and high doses of Xuetong capsules (0.5, 1.0, and 2.0 g/kg) by gavage, and the positive drug control group was given atorvastatin calcium (1.5 mg/kg) by gavage. The model group was given solvent (0.5% carboxymethyl cellulose sodium). After treatment for 8 weeks, the body weight, organ index, blood lipids, blood glucose and liver function index were measured. The liver oil red staining was used to determine the lipid droplet content, and quantitative PCR was used to detect the expression of inflammatory factors TNF-α, IL-6, and IL-1β. Results The body weight, the weight of liver and spleen were significantly increased by high-fat diet. High-fat diet increased the organ indexes of the liver and spleen, the degree of liver oil red staining, and also significantly increased the levels of glucose, triglyceride (TG), cholesterol (CHOL), and low-density lipoprotein cholesterol (LDL-C) in serum. Compared with the model group, the level of TG has no significant change in low, middle and high doses groups. The level of CHOL in serum was reduced by Xuetong capsule with a dose dependent manner. There were significant difference between the model group and middle, high doses groups. The results of LDL-C were similar, the level of LDL-C was significantly reduced by middle and high doses groups [middle dose (0.55±0.21) mmol/L, high dose (0.52±0.22) mmol/L vs (0.81±0.29) mmol/L in model group, P<0.05]. Compared with the normal control, there was no significant difference in HDL-C levels between the high-fat model and each drug-treated group. Liver function showed that Xuetong capsules significantly reduced the degree of liver oil red staining and decreased the level of alanine aminotransferase (ALT) induced by high-fat diet. The body weight, the weight and organ indexes of liver and spleen were significantly reduced by positive drug control group. The levels of CHOL, LDL-C, and TG, and the degree of liver oil red staining were also significantly reduced in positive drug control group. Further studies have shown that high dose of Xuetong capsules significantly reduced the expression of TNF-α and IL-6 induced by high-fat diet (P<0.05), while the reduction of IL-1β was not so significant (P>0.05). Conclusion Xuetong capsules significantly reduced the body weight of animals with high fat, liver size, fat deposition, inflammatory damage and also significantly reduced blood lipid CHOL and LDL-C levels and transaminase elevation. The above effects may be related to Xuetong capsules reducing the expression of inflammatory factors such as TNF-α and IL-6 in the liver.
5.The hypolipidemic function and hepatic protective effects of Xuetong capsules
Lin HE ; Yanqiong CHENG ; Juanjuan ZHAO ; Huilan LU ; Jun YANG ; Fangjian CHEN
Journal of Pharmaceutical Practice and Service 2026;44(6):289-295
Objective To investigate the effects of Xuetong capsule on blood lipids and liver lesion in hyperlipidemic model animals. Methods Sixty ICR mice were randomly divided into six groups. The normal control group was fed with normal diet, the other groups were fed with high-fat diet to induce hyperlipidemia. After four weeks feeding, the three groups were given low, middle, and high doses of Xuetong capsules (0.5, 1.0, and 2.0 g/kg) by gavage, and the positive drug control group was given atorvastatin calcium (1.5 mg/kg) by gavage. The model group was given solvent (0.5% carboxymethyl cellulose sodium). After treatment for 8 weeks, the body weight, organ index, blood lipids, blood glucose and liver function index were measured. The liver oil red staining was used to determine the lipid droplet content, and quantitative PCR was used to detect the expression of inflammatory factors TNF-α, IL-6, and IL-1β. Results The body weight, the weight of liver and spleen were significantly increased by high-fat diet. High-fat diet increased the organ indexes of the liver and spleen, the degree of liver oil red staining, and also significantly increased the levels of glucose, triglyceride (TG), cholesterol (CHOL), and low-density lipoprotein cholesterol (LDL-C) in serum. Compared with the model group, the level of TG has no significant change in low, middle and high doses groups. The level of CHOL in serum was reduced by Xuetong capsule with a dose dependent manner. There were significant difference between the model group and middle, high doses groups. The results of LDL-C were similar, the level of LDL-C was significantly reduced by middle and high doses groups [middle dose (0.55±0.21) mmol/L, high dose (0.52±0.22) mmol/L vs (0.81±0.29) mmol/L in model group, P<0.05]. Compared with the normal control, there was no significant difference in HDL-C levels between the high-fat model and each drug-treated group. Liver function showed that Xuetong capsules significantly reduced the degree of liver oil red staining and decreased the level of alanine aminotransferase (ALT) induced by high-fat diet. The body weight, the weight and organ indexes of liver and spleen were significantly reduced by positive drug control group. The levels of CHOL, LDL-C, and TG, and the degree of liver oil red staining were also significantly reduced in positive drug control group. Further studies have shown that high dose of Xuetong capsules significantly reduced the expression of TNF-α and IL-6 induced by high-fat diet (P<0.05), while the reduction of IL-1β was not so significant (P>0.05). Conclusion Xuetong capsules significantly reduced the body weight of animals with high fat, liver size, fat deposition, inflammatory damage and also significantly reduced blood lipid CHOL and LDL-C levels and transaminase elevation. The above effects may be related to Xuetong capsules reducing the expression of inflammatory factors such as TNF-α and IL-6 in the liver.
6.Construction of a clinical efficacy evaluation system for traditional Chinese medicine treatment of chronic hepatitis B and related reflections
Liyun HE ; Xiaoliang ZHAO ; Lin LUO
Journal of Clinical Hepatology 2026;42(5):998-1003
Traditional Chinese medicine (TCM) is widely used in the clinical management of chronic hepatitis B in China and has exhibited certain advantages in alleviating symptoms, regulating overall physiological status, and assisting in the intervention against disease progression. However, there is still a lack of a comprehensive clinical efficacy evaluation system for TCM treatment of chronic hepatitis B, with inconsistencies in the selection of evaluation indicators and limited objectivity and standardization in the assessment of syndromes and symptoms, which have limited the systematic accumulation of evidence regarding TCM efficacy and the incorporation of TCM into clinical guidelines and expert consensus statements. This article systematically reviews the current status of research on the clinical efficacy evaluation of TCM for chronic hepatitis B and analyzes the achievements made in the field of TCM therapy and integrated traditional Chinese and Western medicine therapy for chronic liver diseases in China’s national major infectious disease research programs during the periods of the Eleventh to Thirteenth Five-Year Plans. It also points out related issues that remain to be addressed and proposes a conceptual framework and specific components for constructing a TCM clinical efficacy evaluation system from the perspectives of evaluation objectives, indicator composition, and application scenarios, in order to provide a reference for the development of related standards, clinical research, and the standardization of integrated traditional Chinese and Western medicine diagnosis and treatment.
7.Value of metabolic markers combined with anthropometric indicators in predicting and risk stratification of metabolic dysfunction-associated fatty liver disease and establishment of a nomogram model
Sirui ZHAO ; Zheyu LI ; Wenqiang HE ; Junfeng LI ; Liting ZHANG
Journal of Clinical Hepatology 2026;42(5):1056-1066
ObjectiveTo develop a novel clinical predictive model for metabolic dysfunction-associated fatty liver disease (MAFLD) based on metabolic markers and anthropometric indicators, and to provide a more effective tool for the early screening and intervention of MAFLD. MethodsA retrospective analysis was performed for 2 824 individuals who underwent abdominal color Doppler ultrasound at Health Examination Center of The First Hospital of Lanzhou University from January 1, 2024 to January 1, 2025, and at a ratio of 7∶3, they were randomly divided into training set with 1 976 patients and validation set with 848 patients. Clinical data, serological markers, and abdominal ultrasound results were collected from all patients, and triglyceride-glucose (TyG) index, triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio, and anthropometric indicators were calculated. The independent samples t-test was used for comparison of normally distributed or approximately normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The multivariate logistic regression analysis was used to identify independent predictive factors for MAFLD and intermediate- to high-risk MAFLD. Five risk prediction models were established for MAFLD based on the independent influencing factors, and a nomogram was plotted. The receiver operating characteristic (ROC) curve was plotted to assess model performance, and the area under the ROC curve (AUC) was calculated. The calibration curve was used to evaluate the predictive accuracy of the models, and decision curve analysis was used to assess the clinical practicability of the models. These models were then compared with traditional models. ResultsAmong the 1 976 individuals in the training set, 937 (47.42%) were diagnosed with MAFLD, and 423 (21.41%) were diagnosed with intermediate- to high-risk MAFLD; among the 848 individuals in the validation set, 406 (47.88%) were diagnosed with MAFLD. The multivariate logistic regression analysis showed that male sex (odds ratio [OR]=0.23, 95% confidence interval [CI]: 0.13 — 0.39, P<0.05), waist circumference (OR=1.11, 95%CI: 1.06 — 1.17, P<0.05), alanine aminotransferase (ALT) >40 U/L (OR=2.24, 95%CI: 1.44 — 3.51, P<0.05), high-density lipoprotein cholesterol (HDL-C) (OR=0.07, 95%CI: 0.04 — 0.15, P<0.05), TyG index (OR=8.27, 95%CI: 5.09 — 13.44, P<0.05), TG/HDL-C ratio (OR=0.84, 95%CI: 0.71 — 0.99, P<0.05), A Body Shape Index (ABSI) (OR=0.45, 95%CI: 0.39 — 0.52, P<0.05), and body roundness index (BRI) (OR=2.31, 95%CI: 1.50 — 3.55, P<0.05) were independent influencing factors for MAFLD, and male sex (OR=0.17, 95%CI: 0.10 — 0.31, P<0.05), age (OR=1.09, 95%CI: 1.07 — 1.11, P<0.05), hemoglobin (OR=0.98, 95%CI: 0.97 — 0.98, P<0.05), platelet count (OR=0.81, 95%CI: 0.70 — 0.93, P<0.05), fasting blood glucose (OR=0.80, 95%CI: 0.71 — 0.89, P<0.05), triglycerides (OR=0.14, 95%CI: 0.07 — 0.29, P<0.05), TG/HDL-C ratio (OR=0.78, 95%CI: 0.67 — 0.91, P<0.05), TyG index (OR=5.26, 95%CI: 3.32 — 8.33), waist circumference (OR=2.50, 95%CI: 1.72 — 3.61, P<0.05), ABSI (OR=0.58, 95%CI: 0.51 — 0.66, P<0.05), and BRI (OR=0.01, 95%CI: 0.00 — 0.21, P<0.05) were independent influencing factors for intermediate- to high-risk MAFLD. Among the five models established, model 5 (incorporating sex, ALT elevation, HDL-C, TyG index, TG/HDL-C ratio, waist circumference, and ABSI) had the best performance, with an AUC of 0.917 (95%CI: 0.905 — 0.929) in the training set and 0.911 (95%CI: 0.892 — 0.930) in the validation set. The calibration curve showed that model 5 had good predictive accuracy, and the decision curve analysis confirmed its clinical practicability. ConclusionThe predictive model for MAFLD constructed based on metabolic markers and anthropometric indicators has good discriminatory ability and can be used to assess the risk of MAFLD. In addition, this study shows that waist circumference, TyG index, TG/HDL-C ratio, ABSI, and BRI are independently associated with intermediate- to high-risk MAFLD, but further studies are needed to confirm their value in predicting liver fibrosis progression.
8.Clinicopathological features and prognostic analysis of vanishing bile duct syndrome
Yangai HE ; Tiandan XIANG ; Chengjie MAO ; Zhonghua LU ; Weifeng ZHAO
Journal of Clinical Hepatology 2026;42(5):1118-1124
ObjectiveTo investigate the differences in clinicopathological features and prognosis between patients with drug-induced vanishing bile duct syndrome (VBDS) and those with VBDS induced by autoimmune liver disease, and to summarize the key points for clinical differentiation. MethodsA total of 67 patients who were diagnosed with VBDS by liver biopsy in The First Affiliated Hospital of Soochow University and Wuxi Fifth People’s Hospital from January 2018 to June 2024 were enrolled as subjects, among whom 18 had drug-induced VBDS (D-VBDS group) and 49 had VBDS induced by autoimmune liver disease (A-VBDS group). Related data were collected, including general information, clinical symptoms and signs, laboratory markers, liver pathomorphological features, and prognosis. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsAmong the 67 VBDS patients, female patients accounted for a higher proportion (80.60%), and the patients aged 40 — 59 years accounted for 55.22%; there were 18 patients (26.87%) with D-VBDS and 49 patients (73.13%) with A-VBDS. Yellow urine (83.58%) was the most common clinical symptom in VBDS patients, followed by fatigue (64.18%), poor appetite (64.18%), jaundice of the sclera (62.69%), abdominal distension (23.88%), pruritus (23.88%), nausea and vomiting (20.90%), and fever (13.43%). Compared with the D-VBDS group, the A-VBDS group had a significantly higher degree of plasma cell infiltration and a significantly lower degree of canalicular bile plugs (χ2=14.186, 6.568, both P<0.05). Compared with the A-VBDS group, the D-VBDS group had significantly higher peak levels of alanine aminotransferase, total bilirubin, direct bilirubin, and indirect bilirubin (Z=-2.546, -2.957, -2.628, -2.772, all P<0.05). Compared with the D-VBDS group, the patients in the A-VBDS group were more likely to develop liver cirrhosis (χ2=4.682, P=0.030). ConclusionThe levels of alanine aminotransferase and bilirubin and liver pathomorphological features are objective indicators for differentiating D-VBDS from A-VBDS, and they are of great importance for clarifying diagnosis and determining the degree of liver injury. Patients with A-VBDS are more likely to develop liver cirrhosis.
9.Characteristics of brain glymphatic system changes in patients with amnestic mild cognitive impairment based on perivascular spaces and DTI-ALPS index assessment
Xiaoqin CHENG ; Guoqiang FEI ; Shen ZHAO ; Rui HUA ; Feng SHI ; Xiaoli PAN ; Ziyi HE ; Sirui LIU
Chinese Journal of Clinical Medicine 2026;33(3):479-485
Objective To explore the characteristics and correlation between perivascular spaces (PVS) and diffusion tensor image analysis along perivascular spaces (DTI-ALPS) index in patients with amnestic mild cognitive impairment (aMCI). Methods A retrospective study was conducted on a total of 118 participants, including cognitive normal (CN) healthy controls and aMCI patients, recruited from the Department of Neurology, Zhongshan Hospital, Fudan University from September 2020 to September 2022. All participants underwent structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). An automatic segmentation algorithm was used to quantify PVS metrics in the brain, and DTI-ALPS index was calculated based on DTI. Differences in DTI-ALPS index and PVS metrics between the CN and aMCI groups were compared. Multivariate logistic regression was used to identify independent factors influencing aMCI. Correlation analysis was performed to assess relationships among DTI-ALPS index, PVS metrics, and cognitive scores. Results A total of 80 CN healthy controls and 38 aMCI patients were included. The DTI-ALPS index was significantly lower in the aMCI group compared with the CN group (1.28±0.18 vs 1.37±0.21, P=0.018), while differences in PVS metrics between groups were not statistically significant. Multivariate logistic regression analysis indicated that DTI-ALPS index was an independent factor affecting aMCI (OR=0.097, 95%CI 0.011–0.833, P=0.033). Correlation analysis revealed a positive relationship between DTI-ALPS index and MMSE score (r=0.210, P=0.023) as well as PVS length in the centrum semiovale (r=0.216, P=0.019). Conclusions The DTI-ALPS index may serve as an imaging biomarker for identifying early cognitive impairment, and patients with aMCI exhibit abnormal DTI-ALPS indices, suggesting that brain glymphatic system dysfunction may occur prior to morphological changes.
10.Molecular Mechanism of Liuwei Dihuangwan Regulating GPNMB Expression and Enhancing Autophagy in Prevention and Treatment of Alzheimer's Disease
Yuxi LIU ; Zhongkang ZHU ; Songnan WANG ; Jiali LIU ; Ye YIN ; Jiarui MIAO ; Shunuo HE ; Danyu ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):1-10
ObjectiveThis study aims to investigate the effect of Liuwei Dihuangwan on the autophagy function in the hippocampus of senescence-accelerated mouse prone 8 (SAMP8) by regulating the expression of glycoprotein non-metastatic melanoma protein B (GPNMB). Furthermore, it is designed to explore the mechanism of the method of tonifying the kidneys and replenishing essence in the treatment of Alzheimer's disease (AD). MethodsIn experiment 1, 24 5-month-old SAMP8 mice were randomly and equally divided into the model group, and the low-, middle- and high-dose(0.59,1.18,2.36 g·kg-1) Liuwei Dihuangwan groups. At the same time, six 5-month-old senescence accelerated mouse resistant 1 (SAMR1) mice were used as the control group. The learning and memory ability was evaluated through novel object recognition experiment. Serum cortisol (Cort), adrenocorticotropic hormone (ACTH) and urine 17-hydroxycorticosteroid (17-OHCS) levels were detected by enzyme-linked immunosorbent assay (ELISA). The ultrastructure of hippocampal neurons was observed by transmission electron microscope (TEM), and the expression levels of hippocampal GPNMB, a disintegrin and metalloproteinase 10 (ADAM10) and autophagy-related proteins were detected by Western blot. In experiment 2, 18 SAMP8 mice were randomly and equally divided into the model group, vector control group (Vector), and GPNMB overexpression group (GPNMBOE). Lentiviral vectors were stereotactically injected into the brain (2 μL per side in the GPNMBOE group). Western blot was used to detect the expression of the above target proteins in the hippocampus; In Experiment 3, 24 SAMP8 mice were randomly and equally divided into the model group, Liuwei Dihuangwan group, Liuwei Dihuangwan+negative control (NC) group, and Liuwei Dihuangwan+GPNMB silencing group (shGPNMB). Before drug treatment, the Liuwei Dihuangwan+NC group and the Liuwei Dihuangwan+shGPNMB group were injected with negative control and GPNMB silencing lentivirus, respectively. Western blot was used to detect the expression of the above target proteins in the hippocampus. ResultsThe novel object discrimination index of mice in the model group was significantly lower than that of mice in the control group (P<0.01). The novel object discrimination index of mice in the medium- and high-dose Liuwei Dihuangwan groups was significantly higher than that of mice in the model group (P<0.01). Aggregated autolysosomes were observed in the normal hippocampus tissue by TEM. In the model group, mitochondria were dominant, and no typical characteristic autophagosomes were observed. In the low- and medium-dose Liuwei Dihuangwan groups, a small number of autolysosomes and autophagosomes with double-membrane structures were observed. In the high-dose Liuwei Dihuangwan group, the number of autophagosomes and autolysosomes was greater than that in the low- and medium-dose groups. The results of ELISA and Western blot showed that compared with the control group, the levels of serum Cort, ACTH, and urine 17-OHCS in the model group were substantially increased, while the expression of hippocampal ADAM10, Beclin1, and microtubule associated-protein light chain 3-Ⅱ/Ⅰ (LC3 Ⅱ/Ⅰ) was significantly decreased. The expression of GPNMB and ubiquitin binding protein p62 was significantly increased (P<0.05, P<0.01). Compared with the model group, the serum Cort and ACTH levels in the low-, medium-, and high-dose Liuwei Dihuangwan groups were significantly reduced, while only the urine 17-OHCS level in the high-dose group was significantly reduced. The hippocampal GPNMB, ADAM10, Beclin1, and LC3 Ⅱ/Ⅰ expression levels in the medium-, and high-dose groups of Liuwei Dihuangwan were significantly increased compared to the model group, whereas the expression of p62 was significantly reduced (P<0.01). The above indicators showed a progressive trend among the three groups. Compared with the model group, the GPNMBOE group showed a significant increase in GPNMB, ADAM10, Beclin1, LC3 Ⅱ/Ⅰ expression, and a significant decrease in p62 expression (P<0.01). Compared with the model group, the expression of GPNMB, ADAM10, Beclin1, and LC3 Ⅱ/Ⅰ in the hippocampus of the Liuwei Dihuangwan group significantly increased, while the expression of p62 significantly decreased (P<0.01). Compared with the Liuwei Dihuangwan group, the Liuwei Dihuangwan+shGPNMB group showed a significant decrease in GPNMB, ADAM10, Beclin1, LC3 Ⅱ/Ⅰ, and a significant increase in p62 expression (P<0.01). ConclusionLiuwei Dihuangwan can enhance hippocampal autophagy function and improve AD by upregulating GPNMB expression.

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