To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Objective To systematically evaluate the efficacy and safety of video-assisted thoracoscopic surgery (VATS) with different numbers of ports in the treatment of spontaneous pneumothorax. Methods We conducted a comprehensive search of CNKI, PubMed, The Cochrane Library, Web of Science, EMbase, Wanfang Data, and the Chinese Medical Journal Full-text Database for clinical controlled trials on VATS with different port numbers for spontaneous pneumothorax, from their inception to March 2023. Two researchers independently screened the literature and assessed its quality.The Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of cohort and case-control studies, and the Cochrane risk-of-bias tool was used to evaluate randomized controlled trials (RCT). Meta-analysis was performed using RevMan 5.4.1 software. Results A total of 107 studies were included, comprising 35 RCT, 2 cohort studies, and 70 case-control studies. All cohort and case-control studies included in the analysis had NOS scores≥7. The meta-analysis revealed that compared to two-port VATS (2P-VATS) and three-port VATS (3P-VATS), single-port thoracoscopic surgery (SPTS) was associated with less intraoperative blood loss (SMD=–1.58, 95%CI: –1.93 to –1.22, P<0.001; and SMD=–1.59, 95%CI: –2.03 to –1.14, P<0.001, respectively), shorter postoperative hospital stay (SMD=–1.05, 95%CI: –1.29 to –0.82, P<0.001; and SMD=–1.08, 95%CI: –1.39 to –0.77, P<0.001), shorter duration of postoperative chest tube drainage (SMD=–0.75, 95%CI: –1.00 to –0.50, P<0.001; and SMD=–1.23, 95%CI: –1.72 to –0.75, P<0.001), fewer postoperative complications (OR=0.34, 95%CI: 0.26 to 0.45, P<0.001; and OR=0.47, 95%CI: 0.33 to 0.68, P<0.001), and lower pain scores at 24, 48, and 72 hours after surgery (P<0.05). The operative time for SPTS was shorter than that for 2P-VATS (SMD=–0.53, 95%CI: –0.90 to –0.16, P=0.005) but showed no significant difference compared to 3P-VATS (P=0.21). When comparing 2P-VATS with 3P-VATS, 2P-VATS demonstrated less intraoperative blood loss (SMD=–1.02, 95%CI: –1.81 to –0.22, P=0.01), shorter postoperative hospital stay (SMD=–0.59, 95%CI: –1.11 to –0.06, P=0.03), shorter duration of chest tube drainage (SMD=–0.46, 95%CI: –0.85 to –0.08, P=0.02), fewer postoperative complications (OR=0.36, 95%CI: 0.22 to 0.59, P<0.001), and lower pain scores at 24, 48, and 72 hours after surgery (P≤0.05). Conclusion Both SPTS and 2P-VATS are effective and safe surgical options for spontaneous pneumothorax, deserving further promotion and application in clinical practice. However, due to limitations in the quantity and quality of the included studies, more large-sample, high-quality research is needed to validate these findings.

Objective To systematically evaluate the efficacy of immune checkpoint inhibitors (ICIs) in treating esophageal cancer patients of different genders. Methods Computer searches were conducted on PubMed, Cochrane Library, and Embase databases to collect randomized controlled trial (RCT) on ICIs treatment for esophageal cancer patients from the establishment of the databases to January 25, 2024. Two researchers independently screened the literature and extracted data according to the inclusion and exclusion criteria. The outcome indicators were overall survival (OS) and progression-free survival (PFS), and RevMan 5.4 software was used for meta-analysis. The modified Jadad scoring scale was used to evaluate the quality of the included literature. Results A total of 10 RCT involving 5364 esophageal cancer patients were included in this study, with 2684 patients in the trial group and 2680 patients in the control group. The Jadad scores of the included literature were all ≥6 points, indicating high-quality RCT. Meta-analysis results showed that female esophageal cancer patients receiving ICIs treatment [HR=0.72, 95%CI (0.59, 0.87), P<0.001] had a more significant median OS prolongation than male patients [HR=0.73, 95%CI (0.68, 0.78), P<0.001]; while male patients [HR=0.57, 95%CI (0.52, 0.64), P<0.001] had a more significant PFS prolongation than female patients [HR=0.72, 95%CI (0.55, 0.94), P=0.01]. Female patients treated with ICIs alone [HR=0.66, 95%CI (0.50, 0.87), P=0.003] had a more significant median OS prolongation than male patients [HR=0.79, 95%CI (0.72, 0.87), P<0.001]; while male patients receiving ICIs combined with chemotherapy [HR=0.67, 95%CI (0.61, 0.74), P<0.001] had a more significant median OS prolongation than female patients [HR=0.77, 95%CI (0.59, 1.01), P=0.06]. Conclusion Female patients receiving ICIs have a slight advantage in OS compared to male patients, while male patients have an advantage in PFS. Male patients receiving ICIs combined with chemotherapy have better survival benefits than female patients, while female patients using ICIs monotherapy have better survival benefits than male patients.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Background: and Purpose Accurately predicting long-term functional outcomes of basilar artery occlusion (BAO) remains challenging. We compared the predictive performance of the baseline, 24-hour, and 72-hour National Institutes of Health Stroke Scale (NIHSS) scores for 90-day BAO functional outcomes using the Acute Basilar Artery Occlusion: Endovascular Thrombectomy versus Standard Medical Treatment (ATTENTION) trial data. We identified the optimal assessment time point, determined treatment-specific NIHSS cutoff values, and explored the role of early neurological function in treatment effects. Methods: This retrospective post hoc analysis included 324 patients with acute BAO with baseline NIHSS scores ≥10 and complete NIHSS assessments at each time point. The primary outcome was a favorable 90-day functional outcome (modified Rankin Scale score, 0–3). Receiver operating characteristic curve analysis was used to assess the predictive ability of NIHSS scores. The optimal 72-hour NIHSS predictive cutoff values were determined for the endovascular treatment (EVT) and best medical management (BMM) subgroups. Results: The 72-hour NIHSS score showed the highest predictive accuracy for the primary outcome (area under the receiver operating characteristic curve [AUC]: 0.954), outperforming the 24-hour (AUC: 0.903) and baseline (AUC: 0.688) scores; its optimal predictive cut-off value was ≤11 in the EVT group (sensitivity: 85.6%, specificity: 92.9%, positive predictive value [PPV]: 91.8%, negative predictive value [NPV]: 87.4%) and ≤9 in the BMM group (sensitivity: 84.6%, specificity: 95.1%, PPV: 84.6%, NPV: 95.1%). Conclusions The 72-hour NIHSS score outperformed the baseline and 24-hour scores in predicting 90-day functional outcomes and mediating the effects of EVT. Treatment-specific 72-hour NIHSS cut-off values may guide early risk stratification and prognostic assessments.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Hyperlipidemic acute pancreatitis(HLAP)is triggered by severe disturbances in lipid metabolism,progresses rapidly,and is associated with a high risk of complications.Its pathogenesis involves multiple mechanisms,including chylomicron accumulation and free fatty acid toxicity,activation of inflammatory pathways,and disruption of intracellular calcium homeostasis.Recent studies have shown that polymorphisms in lipid metabolism-related genes can influence HLAP susceptibility,disease severity,and lipid-lowering drug efficacy by regulating lipoprotein metabolism,fatty acid oxidation,and inflammatory responses.This article systematically reviews the associations between major lipid metabolism gene polymorphisms and HLAP/hypertriglyceridemia,gene-gene and gene-environment interactions,and the potential impact of these polymorphisms on the therapeutic responses to fibrates,statins,and PCSK9 inhibitors.It also discusses the current status and challenges of genotype-based individualized prevention and treatment strategies,aiming to provide a theoretical basis and future directions for precision screening and personalized management of HLAP.

Objective To explore the influence of hsa_circ_0004535 on type 2 diabetes(T2DM)combined with metabolic-associated fatty liver disease(MAFLD)model mice.Methods Forty-eight healthy SPF grade Balb/c mice were selected for modeling and divided into the following groups(n=6 per group):Control group:normal feed;T2DM group:diabetes model induced by high-glucose and high-fat diet;T2DM combined MAFLD group:non-alcoholic fatty liver high-glucose and high-fat diet-induced diabetes combined with fatty liver model;T2DM combined MAFLD+hsa_circ_NC group:after 4 weeks of modeling,10 nmol hsa_circ_NC injected into the tail vein;T2DM combined MAFLD+hsa_circ_0004535 group:after 4 weeks of modeling,10 nmol circ_0004535 injected into the tail vein;T2DM combined MAFLD+miRNA_NC group:after 4 weeks of modeling,10 nmol miRNA blank control injected into the tail vein;T2DM combined MAFLD+miR-1827 agomir group:after 4 weeks of modeling,10 nmol miR-1827 agomir injected into the tail vein;and T2DM combined MAFLD+miR-1827 antagomir group:after 4 weeks of modeling,10 nmol miR-1827 antagomir injected into the tail vein.Mouse body weight was measured after the interventions and recorded weekly.Glucose and insulin tolerance tests were performed,blood lipids and liver function were measured,the liver and insulin resistance indexes were calculated,and pathological tests(hematoxylin/eosin(HE),oil red O,and Masson staining,immunohistochemistry,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL))were performed to measure the degree of hepatic inflammation,fat deposition,and fibrosis.Results(1)Body weight,liver weight,liver index,insulin resistance index,and biochemical indexes were all significantly lower in the hsa_circ_0004535 injection group compared with the hsa_circ_NC injection group and the T2DM combined MAFLD group(both P＜0.05).(2)Steatosis vacuoles were reduced and smaller and inflammatory cell infiltration was reduced in the T2DM combined MAFLD+circ_0004535 group,as shown by HE and oil red staining.(3)TUNEL-positive cells were significantly reduced in the T2DM combined MAFLD+hsa_circ_0004535 group(P＜0.05).(4)Collagen fiber deposition was significantly reduced in the T2DM combined MAFLD+hsa_circ_0004535 group,as shown by Masson staining(P＜0.05).Conclusions The expression of hsa_circ_0004535 and miRNA-1827 play important roles in regulating lipid metabolism,insulin sensitivity,inflammatory pathways,hepatocyte apoptosis,and hepatic fibrosis-related pathways in an animal model of T2DM combined with MAFLD.

Aim To explore the mechanism of the co-lonic mucosa of rats with irritable bowel syndrome(IBS)by regulating the Tongxie Yaofang on mecha-nism of short chain fatty acids(SCFAs)and 5-hydroxytryptamine(5-HT)conversion metabolism.Methods The IBS model rats were established by colorectal stimulating baby rats combined with tempora-ry separation of baby rats and female rats.The IBS rats were divided into low-dose Tongxie Yaofang group,high-dose group,model control group,and normal control group.Transmission electron microscopy was used to observe the ultrastructure of the intestinal mu-cosa;ELISA was used to detect the levels of DAO,D-LA,ET,5-HT and 5-HTP in serum;gas chromatogra-phy was used to detect the levels of SCFAs(acetic,propionic and butyric acids)in feces;immunohisto-chemistry was used to detect the expression levels of TPH1,TRPA,5-HTP,5-HT,TGR5,TLR2,5-HT4R and SERT;Western blot was used to detect the expres-sion of intestinal mucosal tight junction proteins Clau-din-1,ZO-1 and Hcy,and the expressions of TPH1,TRPA,TGR5,TLR2 and SERT in colon tissues were further validated.Results Tongxie Yaofang signifi-cantly increased the protein expression of Claudin-1 and ZO-1 of IBS model rats(P＜0.01),decreased Hcy protein expression(P＜0.01),and reduced lev-els of DAO,D-LA,ET,5-HT and 5-HTP in serum(P＜0.05,P＜0.01).It reduced acetic acid,propionic acid and butyric acid content in feces(P＜0.05,P＜0.01),decreased colonic tissue TPH1,TRPA,5-HTP,5-HT,TGR5,TLR2,5-HT4R expression(P＜0.05,P＜0.01),and increased SERT expression(P＜0.05,P＜0.01).Conclusion Tongxie Yaofang improves the pathology of IBS by promoting the expres-sion of intestinal tight junction proteins,regulating the expression of related proteins in the SCFAs-5-HT trans-lational metabolic system,and repairing the intestinal mucosal barrier function.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.