ObjectiveTo investigate the inhibitory effects and mechanisms of Xiayuxue Tang （XYXT） on hepatocellular carcinoma cells through the regulation of succinate metabolism and succinylation modification. MethodsXYXT-medicated serum was prepared. The effects of different concentrations of succinate on the proliferation of HepG2 and MHCC97H cells were observed using the cell counting kit-8 （CCK-8） assay， and the experimental concentrations for subsequent tests were determined. Further CCK-8 assays were performed to evaluate the effects of XYXT-medicated serum of different concentrations （5%， 10%， and 15%） on cell proliferation. Flow cytometry， scratch test， and Transwell assay were employed to analyze the effect of 10% XYXT-medicated serum on the cell cycle， migration， invasion， and apoptosis. The changes in succinate metabolism and succinylation modification were examined based on succinate content assays， succinate dehydrogenase （SDH） activity detection， and western blot. The expressions of Yes-associated protein 1 （YAP1） and sirtuin 5 （SIRT5） were detected via Real-time PCR and western blot. Molecular docking was applied to validate the binding between XYXT’s main components and target proteins. ResultsCompared with the control group， 1-2 mmol·L^-¹ succinate significantly promoted HepG2 and MHCC97H cell proliferation （P<0.01）. XYXT-medicated serum （5%， 10%， and 15%） markedly inhibited the proliferation of both cell lines compared with the blank group （P<0.05， P<0.01）. Treatment with 10% XYXT-medicated serum arrested the cell cycle at the stage prior to DNA synthesis （G₀/G₁） （P<0.01）， suppressed migration （P<0.01） and invasion （P<0.05， P<0.01）， and promoted apoptosis of HepG2 and MHCC97H cells （P<0.01）. Co-treatment with XYXT and succinate reversed the inhibitory effects of XYXT on proliferation， migration， and invasion of HepG2 and MHCC97H cells （P<0.05， P<0.01）. The proportion of cells at G₀/G₁ phase decreased （P<0.01）， and the apoptosis rate decreased （P<0.01）. In terms of succinate metabolism， compared with the blank serum group， the 10% XYXT-medicated serum reduced succinate levels of HepG2 and MHCC97H cells （P<0.05， P<0.01）， enhanced SDH activity （P<0.01）， and downregulated succinylation modification. In terms of YAP1/SIRT5 pathway， compared with the blank serum group， the 10% XYXT-medicated serum significantly downregulated the mRNA and protein expressions of YAP1 in HepG2 and MHCC97H cells （P<0.05， P<0.01） while significantly upregulated the mRNA and protein expressions of SIRT5 （P<0.05， P<0.01）. Molecular docking confirmed that there was a good binding ability between YAP1 and SIRT5， as well as between XYXT's main active components and YAP1 and SIRT5. ConclusionXYXT suppresses hepatocellular carcinoma cells by modulating the YAP1/SIRT5 signaling axis to intervene in succinate metabolism and succinylation modification.

Compared to traditional suturing, lung stapling using automatic staplers offers advantages such as smaller trauma, faster wound healing, ease of operation, and lower complication rates, making it widely used in clinical practice. However, there are significant differences in bronchial tissue thickness at different anatomical locations, and the market is flooded with various types of staplers. Currently, there is a lack of recommended stapling schemes for bronchial staplers at different anatomical locations. This article reviews the development and application of automatic staplers and summarizes some types of staplers that are currently used in clinical practice, with the aim of promoting the formation of individualized stapler selection protocols for minimally invasive thoracic surgery based on the Chinese population.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

ObjectiveTo analyze the evolutionary characteristics and genetic variations of the HA (hemagglutinin) and NA (neuraminidase) genes of influenza A(H1N1) viruses in Shanghai during 2024, to investigate their transmission patterns, and to evaluate their potential impact on vaccine effectiveness. MethodsFrom January to October 2024, throat swab specimens were collected from influenza like illness (ILI) patients at 4 hospitals in Shanghai. Real-time fluorescence ploymerase chain reaction (RT-PCR) was used for virus detection and isolation of H1N1 influenza viruses. Forty influenza A(H1N1) virus strains were sequenced using Illumina NovaSeq 6000 platform, followed by phylogenetic analyses, genetic distance analysis, and amino acid variation analyses of HA and NA genes. ResultsPhylogenetic tree of the HA and NA genes revealed that the 40 influenza A(H1N1) virus strains circulating in Shanghai in 2024 exhibited no significant geographic clustering, with a broad origin of strains and complex transmission chains. Genetic distance analyses demonstrated that the average intra-group genetic distances of HA and NA genes among the Shanghai strains were 0.005 1±0.000 6 and 0.004 6±0.000 6, respectively, which were comparable to or higher than those observed in global surveillance strains. Both HA and NA genes displayed frequent mutations. Compared to the 2023‒2024 and 2024‒2025 Northern Hemisphere A(H1N1) vaccine strains (WHO-recommended), the HA proteins of 40 Shanghai strains exhibited amino acid substitutions at positions 120, 137, 142, 169, 216, 223, 260, 277, 356 and 451, with critical mutations at positions 137 and 142 located within the Ca2 antigenic determinant. Furthermore, mutations in the NA protein were observed at positions 13, 50, 200, 257, 264, 339 and 382. ConclusionThe genetic background of the 2024 Shanghai influenza A(H1N1) virus strains is complex and diverse, and antigenic variation may affect vaccine effectiveness. Therefore, it is recommended to enhance genomic surveillance of influenza viruses, evaluate vaccine suitability, and implement more targeted prevention and control strategies against imported influenza viruses.

Objective:To investigate the role of Golgi protein 73(GP73)in the diagnosis of primary biliary cholangitis(PBC)and its association with disease progression and therapeutic efficacy monitoring.Methods:Serum samples were collected from 70 PBC pa-tients,36 patients with liver diseases other than autoimmune liver disease(non-AILD group),and 40 healthy controls(HC group),and ELISA was used to measure the serum level of GP73.For the inpatients with PBC,serum samples were collected before and after treat-ment to measure GP73.Results:There was a significant difference in the distribution of serum GP73 concentration between the PBC group,the non-AILD group,and the HC group(P<0.001),and the receiver operating characteristic(ROC)curve showed that GP73 had an area under the ROC curve of 0.839 in the diagnosis of PBC.Serum GP73 level was positively correlated with aspartate amino-transferase(AST)(r=0.337,P=0.009),alkaline phosphatase(ALP)(r=0.380,P=0.003),total bilirubin(r=0.330,P=0.010),and direct bilirubin(r=0.371,P=0.004),while it was negatively correlated with prothrombin activity(r=-0.329,P=0.036)and cholinesterase(r=-0.518,P<0.001).The PBC patients with liver cirrhosis had a significantly higher serum GP73 level than those without liver cirrhosis(P=0.002).There was no significant difference in GP73 content between the patients with positive anti-mitochondrial antibodies-M2,anti-BCOADC-E2PDC-E2 OGDC-E2 antibodies,and anti-SPl00 antibodies and those with negative antibodies.The PBC patients had significant reductions in the serum levels of AST,ALP,gamma-glutamyl transpeptidase,and GP73 after liver-protecting treatment and improvement in cholestasis(P<0.05).Conclusion:GP73 plays an important role in the diagnosis,disease progression,and efficacy monitoring of PBC and is expected to become a potential disease marker for PBC.

Objective:To investigate the effect of Qinggan Bupi Jiangtang Decoction combined with acupuncture on glucose and lipid metabolism and cytokines in patients with overweight/obese T2DM.Methods:Randomized controlled trial. A total of 104 patient with overweight/obese T2DM who were admitted to the Shanghai Municipal Hospital of Traditional Chinese Medicine of Shanghai University of Traditional Chinese Medicine from September 2022 to March 2023 were selected as the research subjects. They were randomly divided into the control group (52 cases) and the combination group (52 cases). The control group was given conventional symptomatic treatment and treated with acupuncture. On this basis, the combination group was treated with Qinggan Bupi Jiangtang Decoction. The two groups were compared in terms of efficacy, TCM syndrome scores, glucose metabolism indicators, islet function indicators, lipid metabolism indicators, cytokines, and blood glucose control. Results:The total effective rate was 90.38% (47/52) in the combined group and 73.08% (38/52) in the control group, and the difference between the two groups was statistically significant ( χ2=5.22, P=0.022). After treatment, the TCM syndrome score (13.21±1.48 vs. 18.54±2.01, t=15.40) of the combination group was lower than that of the control group ( P<0.001). After treatment, the combination group FPG [(6.05 ± 1.01) mmol/L vs. (7.26 ± 1.13) mmol/L, t=5.73], 2 hPG [(8.23 ± 1.12) mmol/L vs. (10.41 ± 1.26) mmol/L, t=9.54], HbAlc [(5.84 ± 0.84) % vs. (6.31 ± 0.93) %, t=2.84] and HOMA-IR (2.57 ± 0.26 vs. 2.86 ± 0.30, t=3.75) were lower than those in the control group ( P<0.05), and HOMA-β (61.34 ± 6.75 vs. 56.69 ± 5.72, t=5.87) was higher than that of the control group ( P<0.05). After treatment, the combination group TC, TG and LDL-C were lower than those in the control group ( t values were 10.25, 5.35, 3.51, respectively, P<0.01), HDL-C was higher than that of the control group ( t=11.59, P<0.01). After treatment, the combination group CTRP12 [(296.05 ± 30.11) ng/L vs. (280.23 ± 28.44) ng/L, t=2.76], FGF-21 [(184.12 ± 19.05) μg/L vs. (170.04 ± 17.03) μg/L, t=2.77], Nesfatin1 [(0.92 ± 0.10) μg/L vs. (0.77±0.08) μg/L, t=5.99] and lipidin levels [(4.89±0.51) mg/L vs. (4.12±0.48) mg/L, t=8.58] were higher than those in the control group ( P<0.01). The combined group composite endpoint achievement rate was 53.85% (28/52), the 12-week HbA1c achievement rate was 80.77% (42/52), and the rate of no weight increase was 84.62% (44/52). The control group's composite endpoint achievement rate was 34.62% (18/52), the 12-week HbA1c achievement rate was 61.54% (32/52), and the rate of no weight increase was 67.31% (35/52). The differences between the two groups were statistically significant ( χ2 values were 3.90, 4.69, 4.27, respectively, and the P values were 0.048, 0.030, 0.039, respectively). The adverse reactions of the two groups were mainly mild nausea, skin rash and pruritus, the incidence of which was 15.38% (8/52) in the combination group and 9.62% (5/52) in the control group, and there was no significant difference between the two groups ( χ2=0.79, P=0.374). Conclusion:The therapeutic effect of Qinggan Bupi Jiangtang Decoction combined with acupuncture on overweight/obese T2DM patients is relatively clear, and it can regulate the glucose and lipid metabolism and cytokines of patients.

In January 2023,the American Heart Association(AHA)released A Scientific Statement:Cancer Therapy Related Hypertension,provided an overview of the mechanisms and clinical management of anticancer therapy related hypertension.Contemporary anticancer drugs are mostly at the expense of cardiovascular toxicities,one of the most common side effects is hypertension,especially vascular endothelial growth factor inhibitors,as well as tyrosine kinase inhibitors and proteasome inhibitors.Cancer therapy related hypertension is often dose limiting,and is usually reversible after interruption or discontinuation of treatment.The exact molecular mechanisms underlying hypertension are unclear,recent discoveries indicate an important role for decreased nitric oxide,increased endothelin-1,endothelial dysfunction,increased sympathetic outflow,and microvascular rarefaction.Based on the International Cardio Oncology Society(IC-OS),this article provides an interpretation of the diagnosis and management of hypertension related to cancer treatment.Insufficient evidence exists supporting an antihypertensive medication strategy specific to patients with anticancer therapy induced hypertension,therefore,antihypertensive management should follow current guidelines for the general population..Multidisciplinary cooperation is needed to optimize management to ensure the optimal therapeutic effect from cancer treatment while minimizing competing cardiovascular toxicities.

Under the new national initiative to rigorously rectify corruption in the medical field,the Discipline Inspection and Supervision Office of the Children's Hospital,Zhejiang University School of Medicine has adopted a multidisciplinary team(MDT)supervision model.Drawing on multidisciplinary administrative practices,the hospital has developed a strategy centered around the establishment of integrity-focused departments and the conduct of work style inspections.This approach is designed to promote the fulfillment of the Party committee's primary responsibility in building a clean and disciplined Party,as well as the supervisory responsibilities of the discipline inspection commission.The model employs a full-process closed-loop management system,which involves identifying issues,urging for corrective actions,and refining systems to ensure accountability and trans-parency.Significant achievements have been made in strengthening the responsibility system,preventing corruption,bolstering work style construction,and delivering targeted anti-corruption education.

AIM:To investigate the effects of skeletal muscle mass on cardiac structure and function in rats subjected to abdominal aortic constriction(AAC),and to explore its potential mechanisms.METHODS:(1)Thirty male SD rats were randomly divided into 3 groups:control(CON)group(n=10),muscular atrophy(MA)group(n=10),and muscular hypertrophy(MH)group(n=10).The rats in MA group underwent bilateral tibial nerve removal to induce MA,while those in MH group engaged in weight-bearing running to promote MH.Four weeks later,skeletal muscle sam-ples were collected,and indicators of MA and MH were assessed.(2)Another rats after modeling above were divided into 4 groups:CON group(n=10),cardiac pathological remodeling group(AAC group;n=10),MA+AAC group(n=10),and MH+AAC group(n=10).All rats,except those in CON group which underwent a sham operation,received AAC sur-gery.Four weeks after surgery,cardiac structure and function were assessed by echocardiography,while morphological changes of the soleus and gastrocnemius muscles and myocardium were evaluated by pathological staining.Serum myo-statin(MSTN)level was measured using ELISA.The mRNA expression levels of atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)in the myocardium,and MSTN in the skeletal muscle and myocardium were detected by real-time PCR.RESULTS:After 4 weeks of either denervation or weight-bearing running,significant atrophy and hyper-trophy of the gastrocnemius and soleus muscles were observed in MA and MH groups,respectively,compared with CON group.However,no significant differences were noted in heart weight/body weight ratio,left ventricular end-diastolic wall thickness,ejection fraction,or other related indexes among these groups(P>0.05).In comparison to AAC group,the rats in MA+AAC group showed a significant increase in heart weight/body weight ratio and left ventricular end-diastolic an-terior wall thickness,a decrease in end-diastolic internal diameter,an increase in ejection fraction(P<0.05 or P<0.01),and exacerbated myocardial fibrosis.Conversely,in MH+AAC group,there was a significant decrease in heart weight/body weight ratio and left ventricular end-diastolic wall thickness,an increase in end-diastolic internal diameter,and a lower ejection fraction(P<0.05 or P<0.01),with reduced myocardial fibrosis.Compared with AAC group,myocardial ANP and BNP mRNA expression significantly increased in MA+AAC group and decreased in MH+AAC group(P<0.01).Additionally,soleus and gastrocnemius muscle MSTN mRNA expression,myocardial MSTN mRNA expression,and se-rum MSTN level significantly increased in MA+AAC group(P<0.01)and significantly decreased in MH+AAC group(P<0.05).CONCLUSION:Atrophic skeletal muscle exacerbated the pathological remodeling induced by AAC surgery,whereas hypertrophic skeletal muscle mitigated this remodeling.Skeletal muscle mass plays a critical role in cardiac patho-logical remodeling,with MSTN potentially regulating this process.