OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia （VaD） model rats. METHODS VaD rat model was established by bilateral common carotid artery ligation. The experimental animals were randomly divided into sham operation group （SHAM）， model group （MOD），Yifei xuanfei jiangzhuo formula low-dose group （YFXF-L）， Yifei xuanfei jiangzhuo formula high-dose group （YFXF-H）， and Donepezil hydrochloride group （positive control）， with 9 animals in each group. After 30 days of intervention， the spatial learning memory ability was assessed by Morris water maze experiment； HE staining was used to observe histopathological changes in CA1 area of hippocampus； ELISA was used to detect the levels of serum inflammatory factors [interleukin-1β （IL-1β） and IL-4]； Western blot was used to detect the expressions of heat shock protein 90 （HSP90）/mixed lineage kinase domain-like protein （MLKL）/dynamin-related protein 1 （Drp1） pathway-related proteins， mitochondrial fusion proteins （MFN1， MFN2）， and adenosine triphosphate synthase 5A （ATP5A） in hippocampal tissues. The immunohistochemistry was used to detect the level of phosphorylated MLKL （p-MLKL）； real-time fluorescence quantitative PCR was adopted to detect mRNA expressions ofHSP90， MFN1， MFN2 and ATP5A. RESULTS Compared with SHAM group， the escape latency of rats in the MOD group was significantly prolonged， the number of crossing the platform was significantly reduced， and the hippocampal tissues showed typical neuronal damage characteristics， the positive expression level of p-MLKL and the serum level of IL-1β significantly increased， while the serum level of IL-4 significantly decreased， the protein and mRNA expression of HSP90， as well as the protein expressions of p-MLKL/MLKL and p-Drp1（Ser616）/Drp1 were all significantly increased in hippocampal tissue， the protein and mRNA expressions of MFN1， MFN2 and ATP5A， and protein expression of p-Drp1（Ser637）/Drp1 were all significantly decreased （P＜0.05）. After the intervention of Yifei xuanfei jiangzhuo formula， above indicators in each treatment group were all significantly reversed （P＜0.05）. CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway， inhibiting mitochondrial fission， thereby maintaining mitochondrial dynamic balance and improving mitochondrial function.

Chronic coronary syndrome(CCS)is one of the most prevalent cardiovascular disease(CVD)in clinical practice.With the accelerating aging of the population and the increasing prevalence of cardiovascular risk factors,CVD has become the leading cause of death among Chinese residents.To optimize diagnosis and treatment strategies through integrated traditional Chinese and Western medicine approaches,and to further improve the clinical management of CCS,the expert group reviewed recent domestic and international guidelines on CCS diagnosis and treatment.Incorporating advances in traditional Chinese medicine(TCM)and leveraging the unique characteristics of Yunnan's local herbal medicine(Yunyao),this consensus document was developed.It aims to guide clinical practice and enhance the overall management of CCS patients in the province.

Ginsenoside Rg_2(GRg2) is a triterpenoid compound found in Panax notoginseng. This study explored its effects and mechanisms on diabetic retinopathy and angiogenesis. The study employed endothelial cell models induced by glucose or vascular endothelial growth factor(VEGF), the chorioallantoic membrane(CAM) model, the oxygen-induced retinopathy(OIR) mouse model, and the db/db mouse model to evaluate the therapeutic effects of GRg2 on diabetic retinopathy and angiogenesis. Transwell assays and endothelial tube formation experiments were conducted to assess cell migration and tube formation, while vascular area measurements were applied to detect angiogenesis. The impact of GRg2 on the retinal structure and function of db/db mice was evaluated through retinal thickness and electroretinogram(ERG) analyses. The study investigated the mechanisms of GRg2 by analyzing the activation of Yes-associated protein(YAP) and Toll-like receptors(TLRs) pathways. The results indicated that GRg2 significantly reduced cell migration numbers and tube formation lengths in vitro. In the CAM model, GRg2 exhibited a dose-dependent decrease in the vascular area ratio. In the OIR model, GRg2 notably decreased the avascular and neovascular areas, ameliorating retinal structural disarray. In the db/db mouse model, GRg2 increased the total retinal thickness and enhanced the amplitudes of the a-wave, b-wave, and oscillatory potentials(OPs) in the ERG, improving retinal structural disarray. Transcriptomic analysis revealed that the TLR signaling pathway was significantly down-regulated following YAP knockdown, with PCR results consistent with the transcriptome sequencing findings. Concurrently, GRg2 downregulated the expression of Toll-like receptor 4(TLR4), TNF receptor-associated factor 6(TRAF6), and nuclear factor-kappaB(NF-κB) proteins in high-glucose-induced endothelial cells. Collectively, GRg2 inhibits cell migration and tube formation and significantly reduces angiogenesis in CAM and OIR models, improving retinal structure and function in db/db mice, with its pharmacological mechanism likely involving the down-regulation of YAP expression.
Animals ; Ginsenosides/pharmacology* ; Diabetic Retinopathy/physiopathology* ; Mice ; YAP-Signaling Proteins ; Humans ; Male ; Signal Transduction/drug effects* ; Cell Movement/drug effects* ; Adaptor Proteins, Signal Transducing/genetics* ; Mice, Inbred C57BL ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Panax notoginseng/chemistry* ; Endothelial Cells/metabolism* ; Transcription Factors/genetics* ; Angiogenesis

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

OBJECTIVE: Objective To investigate the relationship between cervical disc herniation and C₀-C₂ Cobb angle. METHODS: The clinical data of 301 patients with cervical disc herniation from 2020 to 2024 were retrospectively analyzed. The median value of C₀-C₂ Cobb angle measurements from 301 patients was used as the boundary, cervical disc herniation patients were divided into two groups, C₀-C₂ Cobb angle <28.50 group and 151 patients with C₀-C₂ Cobb angle≥28.50 group. Among them, 150 patients in C₀-C₂ Cobb angle <28.50 group included 53 males and 97 females, aged 23 to 76 (57.32±12.55) years, with a disease duration of 7 to 19 (13.81±5.32) months;the othor 151 patients with C₀-C₂ Cobb angle≥28.50 group including 61 males and 90 females, aged 25 to 74 (56.86±12.51) years, with a disease duration of 8 to 18 (14.13±5.56) months. The cervical lordosis angle (C₀-C₂ Cobb angle and C₂-C₇ Cobb angle), T₁ inclination slope (T₁S) and cervical sagittal axial distance (C₂-C₇ SVA) were measured on the lateral cervical radiographs. The correlation between C₀-C₂ Cobb angle and cervical disc herniation range, protrusion position, average protrusion size and other parameters was analyzed. RESULTS: When the C₀-C₂ Cobb angle<28.50°, the average protrusion size was (2.21±0.56) mm, the C₂-C₇ Cobb angle was (19.92±12.06)° and the C₂-C₇ SVA was (1.10±1.20) mm. When the C₀-C₂ Cobb angle≥28.50°, the average protrusion size was (2.38±0.60) mm, the C₂-C₇ Cobb angle was (12.01±13.09 )°, the C₂-C₇ SVA was (1.53±1.36) mm, and the difference was statistically significant (P<0.05). Between the two groups of patients with C₀-C₂ Cobb angle < 28.50° and C₀-C₂ Cobb angle≥28.50°, there were significant differences in the size of C_3,4, C_4,5, C_5,6, C_6,7, C₇, T₁ disc herniation in single segment (P<0.05 ). C₀-C₂ Cobb angle was correlated with age(r=-0.135, P<0.05 ), C₂-C₇ Cobb angle (r=-0.382, P<0.01 ), C₂-C₇ SVA (r=0.293, P<0.01), average protrusion size (r=0.139, P<0.05), and the size of C_3,4 (r=0.215, P<0.01 ), C_4,5 (r=0.176, P<0.01 ), C_5,6 (r=0.144, P<0.05 ), C_6,7 (r=0.158, P<0.05 ), C₇T₁ (r=0.535, P<0.05) disc herniation. CONCLUSION There is a positive correlation between C₀-C₂ Cobb angle and the size of cervical disc herniation. C₀-C₂ Cobb angle can reflect the degree of cervical disc herniation. Previous studies have shown that the biomechanical changes between C₀-C₂ Cobb angle, C₂-C₇ Cobb angle, C₂-C₇ SVA and cervical extensor muscle group may be risk factors for accelerating cervical disc herniation and this may be one of the mechanisms that C₀-C₂ Cobb angle is positively correlated with the size of cervical disc herniation.
Humans ; Male ; Female ; Middle Aged ; Intervertebral Disc Displacement/physiopathology* ; Adult ; Cervical Vertebrae/diagnostic imaging* ; Aged ; Retrospective Studies ; Young Adult

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

Objective:To compare the short-term efficacy of Kamikawa anastomosis and double-tract reconstruction (DTR) after proximal gastrectomy.Methods:This was a propensity score matched, retrospective, cohort study. Inclusion criteria comprised age 20–70 years, diagnosis of gastric cancer by pathological examination of preoperative endoscopic biopsies, tumor diameter ≤4 cm, and location in the upper 1/3 of the stomach (including the gastroesophageal junction), and TNM stage IA, IB, or IIA. The study cohort comprised 73 patients who had undergone laparoscopic proximal gastric cancer radical surgery in the Department of Gastroenterology, Tangdu Hospital, Air Force Medical University between June 2020 and February 2023, 19 of whom were in the Kamikawa group and 54 in the DTR group. After using R language to match the baseline characteristics of patients in a ratio of 1:2, there were 17 patients in the Kamikawa group and 34 in the DTR group. Surgery-related conditions, postoperative quality of life, and postoperative complications were compared between the two groups.Results:After propensity score matching, there were no statistically significant differences in baseline data between the two groups ( P>0.05). Compared with the DTR group, the Kamikawa group had longer operative times (321.5±15.7 minutes vs. 296.8±26.1 minutes, t=32.056, P<0.001), longer anastomosis times (93.0±6.8 minutes vs. 45.3±7.7 minutes, t=56.303, P<0.001), and less bleeding (76 [54~103] mL vs.112 [82~148) mL, Z=71.536, P<0.001); these differences are statistically significant. There were no statistically significant differences between the two groups in tumor size, time to first postoperative passage of gas, postoperative hospital stay, number of lymph nodes removed, duration of lymph node dissection, or total hospitalization cost (all P>0.05). The median follow-up time was 6.1 ± 1.8 months. As to postoperative quality of life, the Kamikawa group had a lower rate of upper gastrointestinal contrast reflux than did the DTR group (0 vs. 29.4% [10/34], χ 2=6.220, P=0.013); this difference is statistically significant. However, differences between the two groups in quality of life score on follow-up of 3 months and 6 months on the Gastroesophageal Reflux Disease (GERD) scale were not statistically significant (all P>0.05). The incidence of postoperative complications was 2/17 in the Kamikawa group, which is significantly lower than the 41.2% (14/34) in the DTR group (χ 2=4.554, P=0.033). Conclusion:Kamikawa anastomosis and DTR are equally safe and effective procedures for reconstructing the digestive tract after proximal gastric surgery. Although Kamikawa anastomosis takes slightly longer and places higher demands on the surgical team, it is more effective at preventing postoperative reflux.

Objective:To explore the application value and surgical experience of neuroendoscopic resection for pediatric patients with cerebellar tumors.Methods:This was a case series study.The clinical data and outcomes of 30 pediatric patients with cerebellar tumors treated through neuroendoscopic surgery in the Department of Neurosurgery, the Guizhou Hospital of Shanghai Children′s Medical Center and Guizhou Provincial People′s Hospital from January 2021 to January 2024 were retrospectively analyzed.Results:Twenty-six patients underwent total resection, 3 patients underwent subtotal resection, and 1 patient underwent biopsy.Postoperative pathological findings showed 9 cases of medulloblastoma, 3 cases of ependymoma, 17 cases of astrocytoma (5 cases of World Health Organization Grade Ⅰ, 3 cases of Grade Ⅱ, and 9 cases of Grade Ⅲ), and 1 case of cerebellar benign lesion.During the perioperative period, malignant arrhythmia occurred and induced death in 1 case, cerebellar mutism occurred in 12 cases, and ataxia occurred in 22 cases.During the 1-36 months of follow-up, 2 cases developed communicating hydrocephalus at the 2 nd and the 6 th month, respectively, and improved after ventriculoperitoneal shunt; cerebellar mutism was relieved to varying degrees after an average postoperative follow-up period of (115±23) days(46-194 days), and ataxia was alleviated after an average postoperative follow-up period of (127±42) days(27-173 days).Tumors relapsed in 5 cases during the last follow-up. Conclusions:Neuroendoscopy provides an alternative to the microscope for experienced operators to achieve the surgical exposure requirements during the resection of pediatric cerebellar vermis tumors.

Objective:To evaluate the efficacy of exercise therapy combined with drug therapy for the treatment of patients with primary osteoporosis based on randomized controlled trial by meta-ananlysis.Methods:Randomized controlled trials of exercise therapy combined with drugs in the treatment of primary osteoporosis published between Jan 1,2000 to Apr 30,2024 in PubMed,EMbase,Cochrane Library,CNKI,VIP were researched.The search strategy combining Medical Subject Headings and free words.After literature screening,quality evaluation and data extraction,meta-analysis was used for quantitative analysis and evaluation.Q test and I2 test were used for heterogeneity test.Subgroup analysis was performed according to the type of drug intervention.Sensitivity analysis was used to evaluate the stability of results,and funnel plot was used to evaluate potential publication bias.Results:A total of 28 literatures were included in this study,including exercise therapy combined with drug therapy group(1 140 cases)and drug therapy alone group(1 136 cases).The results showed that compared with drug therapy alone,exercise therapy combined with drug therapy had statistically significant differences in bone mineral density(BMD)of lumbar vertebra(SMD=1.42,95%CI:1.11-1.73),femur(SMD=1.14,95%CI:0.73-1.56)and hip(SMD=0.59,95%CI:0.09-1.09)(P＜0.05).Exercise therapy combined with drug therapy was also superior in alleviating pain in patients(SMD=-1.94,95%CI:-2.50--1.38,P＜0.05).The results of total subgroup analysis showed statistically significant differences among different drug interventions(P＜0.05).Conclusions:Exercise therapy combined with drug therapy has a good intervention effect on primary osteoporosis.However,due to the small sample size of the included studies,the results still need to be further verified by large sample population studies.