ObjectiveTo develop a standardized classification model for traditional Chinese medicine （TCM） syndrome patterns of mixed hemorrhoids using multi-center real-world data， and unveil their distribution patterns and core risk factors， thereby providing evidence-based support for standardizing TCM syndrome differentiation and implementing precision interventions. MethodsA multi-center cross-sectional study was conducted， enrolling 13 283 mixed hemorrhoid patients from eight hospitals in Jiangsu Province between September 1st， 2023 and December 31st， 2024. DeepSeek-R1-Distill-Qwen-7B and LLaMA-3.3 large language models （LLM） were integrated with latent class analysis （LCA） to perform unsupervised learning and latent class modeling of TCM symptomatology. Potential risk factors were screened via univariate analysis， followed by logistic regression to identify independent risk factors for each syndrome pattern. ResultsThe model's performance indicators were stable and reliable across different clinical data types，i.e. in the outpatient records， past medical history （F1=99.7%）， current medical history （F1=94.9%）， and specialist examination （F1=90.7%）； in inpatient records， past medical history （F1=98.2%）， current medical history （F1=91.2%）， specialist examination （F1=90.3%）， and discharge status （F1=90.6%）. Latent class mode-ling identified four core TCM syndrome patterns including spleen deficiency and qi sinking syndrome （915 cases， 6.89%）， damp-heat pouring downward syndrome （10 820 cases， 81.46%）， qi stagnation and blood stasis syndrome （1252 cases， 9.43%）， and wind injuring intestinal collaterals syndrome （296 cases， 2.22%）， with respective latent class probabilities of 0.069， 0.815， 0.094， and 0.022. Logistic regression demonstrated that gender， age， disease duration， hypertension， diabetes， hyperlipidemia， constipation， smoking history， and alcohol consumption were independent risk factors for pattern differentiation （P＜0.05）. The efficacy validation evaluation revealed that the cure rates for patients with spleen deficiency and qi sinking syndrome and qi stagnation and blood stasis syndrome were higher than those for patients with damp-heat pouring downward syndrome （adjusted P＜0.05）， with no statistically significant differences among other syndrome patterns. ConclusionDamp-heat pouring downward syndrome is the predominant syndrome in mixed hemorrhoids. Gender， age， disease duration， hypertension， diabetes， hyperlipi-demia， constipation， smoking history， and alcohol consumption are independent risk factors for the differentiation of syndrome types.

Aim To investigate the role and regulatory mechanism of CREB regulated transcription coactivator 2(CRTC2)in cardiomyocyte hypertrophy.Methods A pathological cardiomyocyte hypertrophy model was established in C57BL/6 mice by intraperitoneal injection of isoproterenol(ISO),the expression of CRTC2 in cardiac tissue was detec-ted by Western blot.The CRTC2 knockout mice model was constructed,the cardiac function of mice was detected by small animal echocardiography,the collagen fiber content in mice cardiac tissue was detected by Masson staining,the car-diomyocyte hypertrophy related proteins:skeletal muscle α1-actin(ACTA1)and brain natriuretic peptide(BNP),as well as ferroptosis related proteins:acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)in mice cardiac tissue were detected by Western blot,the iron ion content in mice cardiac tissue was detected by iron ion kit,to evaluate the correlation between CRTC2 and cardiomyocyte hypertrophy and ferroptosis.H9c2 cells were induced by ISO to construct an in vitro model of cardiomyocyte hypertrophy,the protein expressions of CRTC2,ACTA1,BNP,ACSL4,SLC7A11 and GPX4 were detected after intervention with fer-roptosis inhibitor ferrostatin-1(Fer-1).H9c2 cells with CRTC2 overexpression induced by ISO were used to construct an in vitro model of cardiomyocyte hypertrophy,the related indicators of cardiomyocyte hypertrophy and ferroptosis were detec-ted to explore the mechanism of CRTC2 in cardiomyocyte hypertrophy.Results Compared with the control group,the expression of CRTC2 protein in the cardiac tissue of ISO induced cardiomyocyte hypertrophy mice was increased(P＜0.05).Compared with wild-type mice,CRTC2-/-mice showed worsened cardiac function,manifested as increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular posterior wall thickness(LVPWT),heart weight/tibia length(HW/TL)and heart weight/body weight(HW/BW),decreased short axis shortening(FS)and ejection fraction(EF),increased collagen fiber content in cardiac tissue,upregulated ex-pression of cardiomyocyte hypertrophy-related proteins ACTA1 and BNP,increased mRNA and protein expression of ferrop-tosis-related protein ACSL4,decreased mRNA and protein expression of SLC7A11 and GPX4,and elevated iron ion content in cardiac tissue(P＜0.05 or P＜0.01).In vitro experiments showed that compared with ISO group,the ISO+Fer-1 group had no significant change in CRTC2 protein expression(P＞0.05),the expression of ACTA1 and BNP protein decreased,the surface area of cardiomyocyte reduced,the expression of ACSL4 protein decreased,and the expression of SLC7A11 and GPX4 proteins increased(P＜0.05 or P＜0.01).Compared with the ISO group,the LV-CRTC2+ISO group showed a decrease in surface area of cardiomyocytes(P＜0.01),a decrease in ACTA1,BNP and ACSL4 protein ex-pression,an increase in SLC7A11 and GPX4 protein expression,and a decrease in ROS and iron ion content(P＜0.05 or P＜0.01).Conclusion CRTC2 alleviates cardiomyocyte hypertrophy and protect cardiac function by suppressing fer-roptosis in cardiomyocytes.

Aim To investigate the role and regulatory mechanism of CREB regulated transcription coactivator 2(CRTC2)in cardiomyocyte hypertrophy.Methods A pathological cardiomyocyte hypertrophy model was established in C57BL/6 mice by intraperitoneal injection of isoproterenol(ISO),the expression of CRTC2 in cardiac tissue was detec-ted by Western blot.The CRTC2 knockout mice model was constructed,the cardiac function of mice was detected by small animal echocardiography,the collagen fiber content in mice cardiac tissue was detected by Masson staining,the car-diomyocyte hypertrophy related proteins:skeletal muscle α1-actin(ACTA1)and brain natriuretic peptide(BNP),as well as ferroptosis related proteins:acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)in mice cardiac tissue were detected by Western blot,the iron ion content in mice cardiac tissue was detected by iron ion kit,to evaluate the correlation between CRTC2 and cardiomyocyte hypertrophy and ferroptosis.H9c2 cells were induced by ISO to construct an in vitro model of cardiomyocyte hypertrophy,the protein expressions of CRTC2,ACTA1,BNP,ACSL4,SLC7A11 and GPX4 were detected after intervention with fer-roptosis inhibitor ferrostatin-1(Fer-1).H9c2 cells with CRTC2 overexpression induced by ISO were used to construct an in vitro model of cardiomyocyte hypertrophy,the related indicators of cardiomyocyte hypertrophy and ferroptosis were detec-ted to explore the mechanism of CRTC2 in cardiomyocyte hypertrophy.Results Compared with the control group,the expression of CRTC2 protein in the cardiac tissue of ISO induced cardiomyocyte hypertrophy mice was increased(P＜0.05).Compared with wild-type mice,CRTC2-/-mice showed worsened cardiac function,manifested as increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular posterior wall thickness(LVPWT),heart weight/tibia length(HW/TL)and heart weight/body weight(HW/BW),decreased short axis shortening(FS)and ejection fraction(EF),increased collagen fiber content in cardiac tissue,upregulated ex-pression of cardiomyocyte hypertrophy-related proteins ACTA1 and BNP,increased mRNA and protein expression of ferrop-tosis-related protein ACSL4,decreased mRNA and protein expression of SLC7A11 and GPX4,and elevated iron ion content in cardiac tissue(P＜0.05 or P＜0.01).In vitro experiments showed that compared with ISO group,the ISO+Fer-1 group had no significant change in CRTC2 protein expression(P＞0.05),the expression of ACTA1 and BNP protein decreased,the surface area of cardiomyocyte reduced,the expression of ACSL4 protein decreased,and the expression of SLC7A11 and GPX4 proteins increased(P＜0.05 or P＜0.01).Compared with the ISO group,the LV-CRTC2+ISO group showed a decrease in surface area of cardiomyocytes(P＜0.01),a decrease in ACTA1,BNP and ACSL4 protein ex-pression,an increase in SLC7A11 and GPX4 protein expression,and a decrease in ROS and iron ion content(P＜0.05 or P＜0.01).Conclusion CRTC2 alleviates cardiomyocyte hypertrophy and protect cardiac function by suppressing fer-roptosis in cardiomyocytes.

OBJECTIVE To assess the efficacy， safety and cost-effectiveness of tenecteplase in the treatment of acute ischemic stroke， and to provide a basis for clinical rational drug use and related decision-making. METHODS The related literature in the PubMed， the Cochrane Library， CNKI， Wanfang data and health technology assessment （HTA） databases were searched from the establishment of the database to June 30th， 2024. Systematic reviews/meta-analyses， pharmacoeconomic studies and HTA reports on tenecteplase in the treatment of acute ischemic stroke were collected. After data extraction and quality assessment， descriptive analysis of the included studies was carried out. RESULTS A total of 31 articles were included， involving 28 systematic reviews/ meta-analysis and 3 pharmacoeconomic studies. In terms of effectiveness， compared with alteplase， tenecteplase （0.25 mg/kg） could significantly increase the early neurological improvement； the 90 d excellent neurological recovery rate， 90 d good neurological recovery rate， and recanalization were not inferior to alteplase. For safety， compared with alteplase， tenecteplase did not increase the incidence of hemorrhage， symptomatic intracranial hemorrhage， 3-month mortality， or intracranial hemorrhage. In terms of cost-effectiveness， foreign research results showed that tenecteplase had economic advantages over alteplase. CONCLUSIONS Compared with alteplase， tenecteplase is effective and safe in the treatment of acute ischemic stroke， and it is cost-effective.

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Objective To explore the general surgery patients with postoperative incision infection(SSI)of pathogenic microorganism distribution characteristics and serum lactate dehydrogenase(LDH),interleukin(IL)-6 to the predictive value of infection.Methods A total of 100 patients who underwent surgery in the General Surgery Department of the hospital from January 2021 to June 2023 were selected as the research ob-jects.According to the occurrence of postoperative infection,the patients were divided into infection group(28 cases)and non-infection group(72 cases).The basic data of the patients were collected,including age,gender,operation type,operation time,incision type,and incision healing.Bacterial culture and pathogen identification were performed on the incision secretion of patients under sterile conditions.At the same time,the serum LDH and IL-6 levels of the patients on the first and third day after operation were detected,and the differences of LDH and IL-6 levels between the infection group and the non-infection group were compared.Pearson cor-relation analysis was used to analyze the correlation between serum LDH level and IL-6.Multivariate Logistic regression analysis was used to analyze the influencing factors of SSI.The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic efficacy of serum LDH and IL-6 levels for SSI.Results A-mong the 100 patients,28 patients developed SSI,and the infection rate was 28％.There were significant differences in age,operation time,and incision type between the infection group and the non-infection group(P＜0.05).The results of bacterial culture showed that a total of 35 strains of bacteria were isolated from the patients in the infection group,of which Gram-positive bacteria accounted for 54.29％and Gram-negative bac-teria accounted for 45.71％,mainly Staphylococcus aureus(14 strains),Pseudomonas aeruginosa(7 strains),and Escherichia coli(5 strains).The serum levels of LDH and IL-6 in the infection group were higher than those in the non-infection group on postoperative days 1 and 3(P＜0.05).The serum level of LDH in the in-fection group was positively correlated with IL-6(r=0.512,P＜0.001).Multivariate Logistic regression a-nalysis showed that age,operation time,type of incision,and serum LDH and IL-6 levels on postoperative day 3 were independent risk factors for SSI(P＜0.05).ROC curve analysis showed that serum LDH and IL-6 lev-els had a high diagnostic efficacy for SSI,with an area under the curve of 0.89 and 0.88,the best cut-off values of 210 U/L and 15 pg/mL,the sensitivity of 82.14％and 85.71％,and the specificity of 78.57％and 80.36％,respectively.Conclusion Staphylococcus aureus and Pseudomonas aeruginosa are the main pathogenic micro-organisms of SSI in general surgical patients.Serum LDH and IL-6 levels can be used as predictors of SSI,which is of great significance for early diagnosis and treatment of infection.

Objective To compare and explore the differences between the eight batches of drugs in the centralized procurement list and the 2018 edition of the national essential medicine list,and to provide reference for updating and improving the national essential medicine list and the national centralized procurement list of drugs.Methods The category,generic name variety,specification,and other information of drugs included in the centralized drug procurement were collected and compared with the 2018 edition of the national essential medicine list,and the reasons for differences were analyzed.Results A proportion of 39%of centralized procurement drugs were listed in national essential medicines.Forty pharmacological classifications were not involved in the drugs of centralized procurement.Only anticoagulant and thrombolytic drugs with dual attributes accounted for a smaller variety proportion than the specification proportion.Conclusion There are some differences between the centralized procurement list and the 2018 edition of the national essential medicine list,which have some rationality,but also some problems to be solved.

OBJECTIVETo investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress, TNF-α and TGF-β1 in rats with diet-induced non-alcoholic fatty liver disease (NAFLD).

METHODSThirty male rats were randomly divided into 3 equal groups and fed for 16 weeks with normal diet (ND), high-fat diet (HFD), or high-fat diet with intraperitoneal injection of liraglutide (GLP-1, administered in the later 4 weeks). The rats were then sacrificed to obtain blood samples and liver tissues for analyzing the levels of blood aminotransferase (ALT), triglyceride (TG), and total-cholesterol (TC) using an automatic biochemical analyzer and the levels of superoxide dismutase (SOD), malondial-dehyde (MAD), free fatty acid (FFAs), TNF-α in the liver homogenates and TGF-β1 in serum by radioimmunoassay or ELISA.

RESULTSCompared with ND group, HFD group showed significantly increased body weight, liver index, serum levels of ALT, TG, TC, and TGF-β1, and TG, TC, MAD, FFAs, and TNF-α in the liver homogenates, with also significantly increased degree of hepatic steatosis and inflammation activity (P<0.05) and lowered level of SOD. All these changes were markedly ameliorated in GLP-1 group (P<0.05).

CONCLUSIONLiraglutide can reduce high-fat diet-induced hepatic steatosis, improve oxidative stress and lipid peroxidation, and decrease TGF-β1 and TNF-α levels in serum and liver homogenates, suggesting its potential as a therapeutic agent for NAFLD.

Alanine Transaminase ; blood ; Animals ; Cholesterol ; blood ; metabolism ; Fatty Acids, Nonesterified ; metabolism ; Hypoglycemic Agents ; pharmacology ; Liraglutide ; pharmacology ; Liver ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Non-alcoholic Fatty Liver Disease ; blood ; metabolism ; pathology ; Oxidative Stress ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Transforming Growth Factor beta1 ; blood ; Triglycerides ; blood ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Objective To investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress, TNF-αand TGF-β1 in rats with diet-induced non-alcoholic fatty liver disease (NAFLD). Methods Thirty male rats were randomly divided into 3 equal groups and fed for 16 weeks with normal diet (ND), high-fat diet (HFD), or high-fat diet with intraperitoneal injection of liraglutide (GLP-1, administered in the later 4 weeks). The rats were then sacrificed to obtain blood samples and liver tissues for analyzing the levels of blood aminotransferase (ALT), triglyceride (TG), and total-cholesterol (TC) using an automatic biochemical analyzer and the levels of superoxide dismutase (SOD), malondial-dehyde (MAD), free fatty acid (FFAs), TNF-αin the liver homogenates and TGF-β1 in serum by radioimmunoassay or ELISA. Results Compared with ND group, HFD group showed significantly increased body weight, liver index, serum levels of ALT, TG, TC, and TGF-β1, and TG, TC, MAD, FFAs, and TNF-a in the liver homogenates, with also significantly increased degree of hepatic steatosis and inflammation activity (P<0.05) and lowered level of SOD. All these changes were markedly ameliorated in GLP-1 group (P<0.05). Conclusion Liraglutide can reduce high-fat diet-induced hepatic steatosis, improve oxidative stress and lipid peroxidation, and decrease TGF-β1 and TNF-a levels in serum and liver homogenates, suggesting its potential as a therapeutic agent for NAFLD.

Objective To investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress, TNF-αand TGF-β1 in rats with diet-induced non-alcoholic fatty liver disease (NAFLD). Methods Thirty male rats were randomly divided into 3 equal groups and fed for 16 weeks with normal diet (ND), high-fat diet (HFD), or high-fat diet with intraperitoneal injection of liraglutide (GLP-1, administered in the later 4 weeks). The rats were then sacrificed to obtain blood samples and liver tissues for analyzing the levels of blood aminotransferase (ALT), triglyceride (TG), and total-cholesterol (TC) using an automatic biochemical analyzer and the levels of superoxide dismutase (SOD), malondial-dehyde (MAD), free fatty acid (FFAs), TNF-αin the liver homogenates and TGF-β1 in serum by radioimmunoassay or ELISA. Results Compared with ND group, HFD group showed significantly increased body weight, liver index, serum levels of ALT, TG, TC, and TGF-β1, and TG, TC, MAD, FFAs, and TNF-a in the liver homogenates, with also significantly increased degree of hepatic steatosis and inflammation activity (P<0.05) and lowered level of SOD. All these changes were markedly ameliorated in GLP-1 group (P<0.05). Conclusion Liraglutide can reduce high-fat diet-induced hepatic steatosis, improve oxidative stress and lipid peroxidation, and decrease TGF-β1 and TNF-a levels in serum and liver homogenates, suggesting its potential as a therapeutic agent for NAFLD.