ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang （BXT） inhibits epithelial-mesenchymal transition （EMT） in chronic atrophic gastritis （CAG） rats by regulating the interleukin-17（IL-17）/extracellular regulated protein kinases（ERK）/CCAAT enhancer binding protein β（C/EBPβ）signaling pathway， thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling， the rats were randomly divided into the model group， low-， medium-， and high-dose groups （0.549， 1.098， 2.196 g·kg^-1， respectively） of BXT， and the positive drug group （vitacoenzyme， 0.3 g·kg^-1）. A normal control group was also set up. After 8 weeks of intervention， the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of IL-17， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2）， and C/EBPβ in serum， as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin， N-cadherin， and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17， p-ERK， and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ， ERK， and its phosphorylated form （p）-ERK in gastric mucosa. Real-time polymerase chain reaction （Real-time PCR） was applied to measure the mRNA expression levels of ERK， COX-2， and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group， the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly increased （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBPβ in serum were significantly increased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased， while the content of E-cadherin was significantly decreased （P<0.01）. Compared with the model group， after intervention with different doses of BXT， the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly reduced （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBP β in serum were significantly decreased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased， while the content of E-cadherin was increased （P<0.05，P<0.01）. ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum， regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

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.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

OBJECTIVE To investigate the clinical characteristics of euglycemic diabetic ketoacidosis （euDKA） induced by empagliflozin， and provide references for safe medication. METHODS Case reports of euDKA induced by empagliflozin were retrieved and analyzed from PubMed， Web of Science， CNKI， and Wanfang Data. The Naranjo’s scale was adopted to assess the causal relationship between empagliflozin and euDKA. RESULTS A total of 29 patients were enrolled， including 16 males and 13 females，with a median age of 58 years. All patients were diagnosed with type 2 diabetes mellitus； 22 patients had at least one comorbidity. The median time to euDKA onset was 60 days after administration， and 7 cases occurred within 2 weeks of treatment. Perioperative periods，fasting，and low-carbohydrate or ketogenic diets were the main predisposing factors. Common presentations included nausea，vomiting， fatigue， tachypnea，and tachycardia. The causal relationship between empagliflozin and euDKA was assessed as “probable” in all cases. According to adverse reaction severity grading， 13 cases were grade 3 （severe） and 16 cases were grade 4 （life-threatening）. All patients discontinued empagliflozin and recovered after corresponding treatment. CONCLUSIONS euDKA is a serious adverse reaction to empagliflozin， which mostly occurs early in treatment. Perioperative periods， fasting， and ketogenic diets are prone to induce euDKA. Elderly patients and those with comorbidities are at higher risk. Risk assessment should be conducted before clinical administration； blood ketones and acid-base monitoring should be strengthened in the early medication period； withhold the drug before elective surgery， avoid prolonged fasting；upon diagnosis， discontinue empagliflozin and initiate intravenous insulin， provide fluid resuscitation promptly， and use other treatments to improve patient prognosis.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

Objective:To explore a simple emergency management method for elderly patients with sigmoid volvulus.Methods:The clinical data of 22 elderly patients (>70 years) with sigmoid volvulus from January 2020 to March 2024 in the Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. All patients were treated with a self-made simple closed-loop enema decompression kit. The abdominal circumference, white blood cell count and C-reactive protein (CRP) before treatment and 12 h after tube placement were measured. The patients were followed for 3 months, and the recurrence was recorded. The key indexes on recurrence, including age, American Society of Anesthesiologists (ASA) classification and procedure time, were compared. Pearson correlation analysis was used to examine the relationship between age, procedure time, pain level and gas/stool output within 30 min after tube placement.Results:All 22 patients successfully underwent transanal tube decompression. The procedure time ranged from 1 to 15 min. The gas and stool output within 30 min after tube placement was 600 to 2 100 ml, The rectal tube was retained for 2 to 6 d. Compared with before treatment, the abdominal circumference, white blood cell count and CRP 12 h after tube placement were significantly lower: (85.9 ± 9.6) cm vs. (94.5 ± 10.2) cm, (9.2 ± 2.1) ×10 9/L vs. (11.4 ± 2.5) ×10 9/L and (27.8 ± 22.6) mg/L vs. (46.2 ± 38.9) mg/L, and there were statistical differences ( P<0.01). Four patients underwent elective surgery, while 18 were discharged smoothly after tube removal. No death occurred within 1 month after treatment. Five patients experienced recurrence 3 months after treatment, all were successfully retreated using the same method and discharged. There were no statistical differences in recurrence rates between aged ≥80 years and aged < 80 years patients, ASA class ≥ Ⅳ and ASA class Ⅲ patients, or procedure times ≤5 min and procedure times >5 min patients ( P>0.05). The gas/stool output within 30 min after tube placement was positively correlated with pain level (moderate/severe vs. mild) before tube placement ( r = 215.50, P = 0.015), but showed no significant correlation with age or procedure time ( P>0.05). Conclusions:The self-made simple closed-loop enema decompression kit provides a straightforward, economical and minimally invasive emergency treatment method for elderly patients with sigmoid volvulus. For patients at very high surgical risk, this kit can achieve decompression and volvulus reposition, even in cases of recurrence.

Objective:To investigate the clinical value of right-sided overlap and single-flap valvuloplasty (ROSF) in Da Vinci robotic proximal gastrectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 12 patients who underwent ROSF in Da Vinci robotic proximal gastrectomy at The Affiliated Hospital of Xuzhou Medical University from September 2023 to May 2024 were collected. There were 7 males and 5 females, aged 62(range, 35?75)years. Observation indicators: (1) surgical conditions; (2) postoperative pathological results; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and mea-surement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers. Results:(1) Surgical conditions. All patients successfully completed the surgery, without conversion to laparotomy. The operation time of 12 patients was (236±24)minutes. The time of single-layer fabrication and anastomosis was (105±28)minutes. The volume of intra-operative blood loss was (36±19)mL. Time to postoperative first fluid food intake was (3.5±1.1)days. The amylase levels in the abdominal drainage fluid on postoperative days 1, 2, and 3 were (321±121)U/L, (225±97)U/L, and (85±22)U/L, respectively. Time to postoperative drainage tube removal was (5.3±1.5)days. Duration of postoperative hospital stay was (7.6±1.1)days. All 12 patients had no anasto-motic related complications such as anastomotic leakage, anastomotic bleeding, anastomotic stenosis, and had no functional complications such as gastric emptying disorders or gastroesophageal reflux after surgery. (2) Postoperative pathological results. The distance of the proximal tumor margin of the 12 patients was (1.8±1.1)cm. The distance of distal margin was (5.7±2.1)cm. Number of lymph node dissected was 31.0(range, 22.0?45.0). Number of positive lymph node dissected was 3.4±2.4. Number of lymph node dissected from the pancreatic superior margin was 14.7±4.3. Results of postoperative pathological examination in the 12 patients showed 8 cases of Ⅰ stage, 3 cases of Ⅱ stage, 1 case of Ⅲ stage of the TNM staging. (3) Follow-up. All 12 patients were followed up for 6 (range, 3?24)months. During the follow-up period, all 12 patients had no local tumor recurrence or distant metastasis. All 12 patients had no complications such as anastomotic leakage, anastomotic bleeding, or anastomotic stenosis, and did not experience symptoms of gastroesophageal reflux such as heartburn or vomiting.Conclusion:The ROSF in Da Vinic robotic proximal gastrectomy is safe and feasible.

Chronic pancreatitis is a chronic inflammatory disease characterized by progre-ssive fibrosis of pancreatic tissue. Its pathological features primarily include parenchymal fibrosis, intraductal stone formation or calcification deposits, as well as segmental stenosis and dilation of the pancreatic duct. Prolonged chronic inflammatory stimulation not only leads to progressive pancreatic dysfunction but may also trigger the formation of pancreatic pseudocysts and even malignant transformation. In the comprehensive treatment of chronic pancreatitis, the core clinical goals are the removal of pancreatic duct stones, restoration of unobstructed pancreatic duct drainage, and preservation of residual pancreatic function. Traditional treatment strategies have been based on the principle of progressive intervention and early surgical management. In recent years, with advancements in extracorporeal shock wave lithotripsy, the application of new techniques such as endoscopic retrograde cholangiopancreatography combined with laser lithotripsy under direct cholan-gioscopic visualization, and improvements in pancreas-preserving surgical approaches, the debate over the superiority of progressive intervention versus early surgical treatment has intensified. Against this backdrop, the treatment mode of Xi′an Jiaotong University Pancreatic Disease Center (hereinafter referred to as "Western Pancreas") has emerged, emphasizing a personalized, multimodal treatment strategy based on different types of pancreatic duct stones. The treatment mode of "Western Pancreas" integrates lithotripsy, endoscopic treatment, and surgical interventions to optimize patient outcomes. By conducting a comprehensive analysis of domestic and international pancreatic duct stone classi-fication systems and drawing from our team′s clinical experience in managing over a thousand cases of chronic pancreatitis, the authors have further refined and proposed a classification system for pancreatic duct stones under the treatment mode of "Western Pancreas". This refinement aims to enhance the overall diagnostic and therapeutic standards for chronic pancreatitis.

BACKGROUND:Nerve growth factor plays an important role in the physiological and pathological processes of bone tissue.Systematic analysis of the effects of nerve growth factor on bone tissue is of great significance in both tissue engineering and clinical treatment.OBJECTIVE:To investigate the regulation of bone formation process by nerve growth factor through pathways such as bone tissue cells and bone nerve-vessel coupling,as well as to study the role of nerve growth factor in the pathological process of bone-related diseases.METHODS:The authors searched for relevant articles in CNKI,WanFang,and PubMed with the keywords of"nerve growth factor,TrkA,NGF,bone,cartilage"in Chinese and English.A total of 2 925 articles were initially retrieved.After screening,116 articles were incorporated into this review.RESULTS AND CONCLUSION:Nerve growth factor can be expressed by bone,cartilage,nerve,vessel and other tissue cells.At the same time,nerve growth factor can play a regulatory role on these cells.Through a variety of secretion and regulation methods,nerve growth factor plays a role as a signal transduction factor within bone tissue and between bone,nerve and blood vessel tissues.By promoting the proliferation and differentiation of bone marrow mesenchymal stem cells,nerve growth factor promotes bone formation and bone repair.Nerve growth factor has multi-directional regulatory effects on bone tissue through its effects on osteoclasts.Meanwhile,nerve growth factor is highly correlated with the occurrence and development of many orthopedic diseases and may provide new clinical therapeutic ideas.The study of nerve growth factor is one of the important directions to understand the physiological and pathological processes of bone.