Objective To analyze the disease burden and trends of bladder cancer in China and globally from 1992 to 2021.  Methods Using the GBD 2021 database, the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates of bladder cancer in China and globally from 1992–2021 were analyzed. Average annual percentage change (AAPC) was calculated using Joinpoint regression. Subgroup analyses by sex and age were conducted, and a Bayesian age-period-cohort (BAPC) model was used to predict trends in age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) for the next 15 years.  Results In 2021, China reported 106 000 new cases (ASIR: 5.14/100 000), 571 000 prevalent cases (age-standardized prevalence rate, ASPR: 26.61/100 000), 43 000 deaths (ASMR: 2.34/100 000), and a DALY rate of 45.31/100 000. From 1992–2021, China showed upward trends in ASIR and ASPR but declines in ASMR and DALYs, while global ASIR, ASMR, and DALYs decreased overall with slow ASPR growth. The peak cases in China and globally were both concentrated in the 65-79 age group, with a significantly higher burden on males than females. In China, smoking-related ASMR and ASDR exceeded global averages and rose, whereas high glucose-related indexes were lower and declined. Projections for 2021–2036 indicated that the global incidence and mortality rates would be rising, but ASIR/ASPR would be declining, while in China, the incidence rate would continue to rise, and the mortality rate will stabilize, with a significant increase in ASIR and a gradual decrease in ASPR.  Conclusion From 1992 to 2021, the incidence of bladder cancer in China has shown a continuous upward trend and is projected to persist in the future, with significant gender and age differences. Particular attention should be given to elderly males aged 85-89. The disease burden of bladder cancer attributable to smoking continues to rise, highlighting the urgent need to strengthen tobacco control policies.

With the rapid development of minimally invasive techniques in surgery, arti-ficial intelligence (AI), particularly deep learning, is playing an increasingly important role in mini-mally invasive surgery. By automated analysis of surgical videos, AI can efficiently perform key tasks such as instrument recognition, surgical phase identification, action analysis, anatomical structure recognition, intraoperative diagnosis, adverse event monitoring and smart desmoking. These appli-cations provide essential support for real-time monitoring, surgical navigation and skill assessment during surgery. The authors summarize the current research progress of AI in minimally invasive surgery, including its applications in the fields of hepatobiliary and pancreatic surgery, as well as gastrointestinal surgery. It also explores the potential of AI in enhancing surgical safety, efficiency and skill assessment. By synthesizing the latest research achievements of AI technology in the field of surgery, as well as analyzing its technical challenges and risks, it aims to provide guidance for future innovations and clinical applications, promoting the advancement and implementation of AI in minimally invasive surgery.

Objective To investigate the therapeutic effect of Gypenoside L(Gyp-L)on diabetic retinopathy(DR)rats and its effect on the p38 mitogen-activated protein kinase(MAPK)signaling pathway.Methods Rats were divided into 6 groups(n=12):blank group,model group,low,medium,high dose group and combination group.The blank group was normal control rats,and the other groups were DR rat models.Rats in the blank group and model group were intragastrically administered with sodium carboxymethyl cellulose.Rats in the low,medium and high dose group were ga-vaged with 50,100,and 200 mg·kg-1·d-1 of Gypenoside L solution,respectively.Rats in the combination group were gavaged with 200 mg·kg-1·d-1 of Gypenoside L solution,and 2 mg·kg-1·d-1 of p38 MAPK agonist Anisomycin was in-jected into the tail vein.The rats in each group were gavaged with a volume of 2 mL per day for a total treatment period of 4 weeks.After the treatment,fundus photography was performed on the rats in each group,and retinal tissues were stained with hematoxylin and eosin(HE).Fasting blood glucose was measured using a Roche blood glucose meter,and se-rum insulin levels were measured using an ELISA kit.Retinal superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin(IL)-1 β,and IL-6 levels were measured according to the instructions of the kit.Western blot was used to detect the protein levels of p38 MAPK,p-p38 MAPK,p65 nuclear factor-κB(NF-κB),p-p65 NF-κB,inducible nitric oxide synthase(iNOS),and cyclooxygenase(COX-2)in the retina.Results Compared with the model group,the blood glucose level was decreased,the serum insu-lin level was increased,the fundus neovascularization was reduced,the retinal damage was alleviated,the retinal SOD,CAT and GSH-Px levels were increased,the MDA level was decreased,the TNF-α,IL-1β and IL-6 levels were decreased,and the p-p38 MAPK,p-p65 NF-κB,iNOS and COX-2 protein levels were decreased in the low,medium and high dose group(all P＜0.05).Compared with the high dose group,the blood glucose level in the combination group was increased,the serum insulin level was decreased,the fundus neovascularization increased,the retinal damage was aggravated,the ret-inal SOD,CAT and GSH-Px levels were decreased,the MDA level was increased,the TNF-α,IL-1[3 and IL-6 levels were in-creased,and the p-p38 MAPK,p-p65NF-κB,iNOS and COX-2 protein levels were increased(all P＜0.05).Conclusion This study shows that Gypenoside L can reduce inflammation and oxidative stress by blocking the p38 MAPK signaling path-way,thereby playing a role in the treatment of DR.

Based on network pharmacology,molecular docking,and experimental validation,this study explored the mechanism by which Hypericum japonicum Thunb-Prunella vulgaris treat liver injury.Mice were randomly divided into four groups:a control group(CON),a model group(CCl4),a high-dose drug group(TXD-H),and a low-dose drug group(TXD-L).A mouse liver in-jury model was established using CCl4 induction.The pathological morphology of liver tissue was observed,and the serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were measured.Active ingredients of traditional Chinese medicine and targets related to these medicines and diseases were obtained from databases such as TCMSP,PubChem,Swiss Tar-get Prediction,GeneCards,and DisGeNET.The intersection of these targets was used to identify potential drug targets.A network diagram illustrating the relationships between"drug-active com-ponent-intersection target"was constructed using Cytoscape.Potential targets were analyzed using the STRING database for protein-protein interaction(PPI)analysis and the DAVID database for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking validation was performed using AutoDock Tools software.Subsequently,key target genes,including those related to the NLRP3 inflammasome and pyroptosis,were detected to validate the molecular docking results.Animal experimental results showed that compared to the CON group,serum AST and ALT activities in the CCl4 group mice were significantly increased(P＜0.01),while in the TXD-L group,serum AST and ALT activities were significantly decreased(P＜0.05)compared to the CCl4 group,and in the TXD-H group,AST and ALT activities were significantly decreased(P＜0.01).Through network pharmacology,135 potential targets were i-dentified,with key components found to be tetramethoxyluteolin,quercetin,kaempferol,luteolin and morin based on degree values,and key targets including TNF,SRC,AKT1,EGFR and ESR1.GO enrichment analysis yielded 304 entries,while KEGG enrichment analysis identified 91 biologi-cal pathways.Molecular docking results demonstrated strong binding between the main compo-nents of Hypericum japonicurn Thunb-Prunella vulgaris and key targets.qPCR results showed that compared to the CON group,the CCl4 group exhibited upregulated relative expression levels of SRC,EGFR,TNF-α,AKT1,and IL-18 mRNA,with significant increases in MyD88,NF-κB,IL-1β,NLRP3,Caspase-1,and ASC mRNA(P＜0.05),and significant upregulation of TLR4 and GS-DMD mRNA(P＜0.01).Compared to the CCl4 group,the TXD-H group displayed significant downregulation of EGFR,AKT1,TLR4,IL-1β,and GSDMD mRNA(P＜0.01),significant decrea-ses in TNF-α,MyD88,NF-κB,NLRP3,and ASC mRNA(P＜0.05),while SRC,IL-18,and Caspase-1 mRNA showed a downward trend.In conclusion,Hypericum japonicum Thunb-Prunel-la vulgaris exerts hepatoprotective effects through multiple components and pathways,among which inhibition of the NF-κB-NLRP3 pathway to reduce hepatocyte pyroptosis may be one of the important pathways for its protective effects.

Objective To explore the value of integrating CT image features and quantitative dual-energy computed tomography(DECT)parameters in predicting cervical lymph nodes metastasis from laryngeal and hypopharyngeal squamous cell carcinoma(LHSCC).Methods The clinical and imaging data of 99 patients with LHSCC confirmed by pathology were retrospectively analyzed.All patients were divided into metastatic group(41 cases)and non-metastatic group(58 cases).The CT image features,including location,size and depth,were analyzed,respectively.The quantitative DECT parameters in the arterial and venous phases including iodine concentration(IC)and normalized iodine concentration(NIC)were measured.The rank sum test or independent-samples t-test were used to compare the difference of CT image features and quantitative DECT parameters between the two groups.The multivariate logistic regression analysis was used to build the models based on CT image features(image feature model)and combination of CT image features and quantitative DECT parameters(combined model).The receiver operating characteristic(ROC)curve was performed to analyze and compare the difference of predictive efficiency between the two groups.Results There were significant differences in tumor location between the non-metastatic group and the metastatic group(χ2=21.736,P<0.001).Size(33.20 mm vs 24.95 mm,P<0.001),depth(21.10 mm vs 13.15 mm,P<0.001)and NIC in the arterial phase(0.18 vs 0.14,P<0.001)in the metastatic group were significantly higher than those in the non-metastatic group.The area under the curve(AUC),sensitivity,specificity,positive predictive value,negative predictive value,accuracy of the combined model were 0.851,75.6%,82.8%,58.5%,87.9%and 75.8%for predicting cervical lymph nodes metastasis.The AUC,sensitivity,specificity,positive predictive value,negative predictive value,accuracy of the image feature model were 0.792,95.1%,56.9%,53.7%,81.0%and 69.7%,respectively.The prediction performance of the combined model was better than that of the image feature model(Z=-2.028,P=0.043).Conclusion Integrating CT image features and quantitative DECT parameters has important value for predicting cervical lymph nodes metastasis from LHSCC.

Objective:To correlate serum bone morphogenetic protein-2 (BMP-2) and cartilage oligomeric matrix protein (COMP) levels with joint function and systemic inflammatory response in patients with knee osteoarthritis (KOA) complicated by cartilage injury.Methods:This study is a retrospective analysis. It selected 258 patients with knee osteoarthritis who were treated at Yantai Yuhuangding Hospital from January 2022 to December 2023. All patients underwent arthroscopic examination. Based on the presence of cartilage injury, 118 patients with cartilage injury were included in the Group A, while 140 patients without cartilage injury were included in the Group B. Joint function (WOMAC Osteoarthritis Index, Lysholm Knee Function Score), serum levels of BMP-2 and COMP, and systemic inflammatory responses [levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α)] were compared between the two groups. Receiver Operating Characteristic (ROC) curves were drawn to analyze the diagnostic efficacy of serum BMP-2 and COMP levels for KOA complicated by cartilage injury. Pearson correlation analysis was used to assess the correlation between the aforementioned serum markers and the patients' WOMAC Osteoarthritis Index, Lysholm Knee Function Score, as well as serum levels of IL-1, IL-6, and TNF-α.Results:Group A had significantly lower serum BMP-2 levels and Lysholm Knee Function Scores compared with Group B [(9.18 ± 1.65) ng/L vs. (11.43 ± 2.51) ng/L, t = 8.34, P < 0.001; (80.06 ± 8.34) vs. (86.94 ± 7.21), t = 7.11, P < 0.001]. Group A exhibited higher serum levels of COMP, IL-1, IL-6, and TNF-α, as well as a higher WOMAC Osteoarthritis Index, with all differences being statistically significant [(6.88 ± 2.34) μg/L vs. (5.04 ± 1.01) μg/L, t = -8.34, P < 0.001; (43.18 ± 7.81) ng/L vs. (35.96 ± 5.02) ng/L, t = -8.96, P < 0.001; (34.03 ± 6.68) ng/L vs. (28.75 ± 5.61) ng/L, t = -6.90, P < 0.001; (13.17 ± 1.89) ng/L vs. (11.24 ± 1.01) ng/L, t = -10.44, P < 0.001; (137.18 ± 18.95) vs. (121.14 ± 13.58), t = -7.90, P < 0.001]. ROC curve analysis indicated that the area under the curve values for serum BMP-2 and COMP levels in diagnosing KOA complicated by cartilage injury were 0.773 and 0.811, respectively. Pearson correlation analysis revealed a negative correlation between serum BMP-2 levels and the WOMAC Osteoarthritis Index, as well as serum levels of IL-1, IL-6, and TNF-α ( r = -0.52, -0.42, -0.40, -0.57, all P < 0.05). Additionally, serum BMP-2 levels showed a positive correlation with the Lysholm Knee Function Score ( r = 0.51, P < 0.05). Serum COMP levels and the WOMAC Osteoarthritis Index were positively correlated with serum IL-1, IL-6, and TNF-α levels ( r = 0.48, 0.45, 0.37, 0.54, all P < 0.05) and were negatively correlated with the Lysholm Knee Function Score ( r = -0.51, P < 0.05). Conclusions:Serum BMP-2 and COMP levels have certain diagnostic value in patients with KOA complicated by cartilage injury. Moreover, these indicators are correlated with joint function and systemic inflammatory responses. Therefore, they hold promise as potential indicators for assessing disease progression in patients with KOA.

Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Objective:To analyze the dynamic changes of serum exosome miR-552 and miR-653 levels in pa-tients with gastric cancer before and after chemotherapy and their relationship with clinical benefit.Methods:IA total of 128 patients with gastric cancer received chemotherapy from January 2022 to January 2024.According to the chemo-therapy effect,the two groups were divided into disease progression group and disease remission group.The levels of serum exosome miR-552 and miR-653 before and after chemotherapy were detected in the two groups,the risk fac-tors affecting the chemotherapy effect of gastric cancer patients were screened,the risk nomogram model was con-structed,and the efficacy was evaluated.Results:The proportion of TNM stage(Ⅲ+Ⅳ),lymph node metastasis,dis-tant metastasis,tumor size(>5 cm),invasion depth(T3/T4)and tumor growth pattern(invasive type)in disease progres-sion group was higher than that in disease remission group(P<0.05).The levels of serum exosomes miR-552 and miR-653 in disease progression group were higher than those in remission group before and after chemotherapy(P<0.05).Compared with before chemotherapy,miR-552 and miR-653 levels in both groups decreased(P<0.05).Logistic regres-sion analysis showed that TNM stage,lymph node metastasis,distant metastasis,tumor size,invasion depth,miR-552 and miR-653 were all risk factors affecting the chemotherapy efficacy of gastric cancer(P<0.05).ROC curve results showed that the AUC,95%CI,sensitivity and specificity of risk nomogram model to predict chemotherapy efficacy of gastric cancer were 0.867,0.672～0.991,92.80%and 80.40%,respectively(P<0.001).Calibration curve results showed that both predicted and actual predicted values were near the ideal curve,and the Hosmer-Lemeshow goodness of fit curve test χ2=1.869,P=0.782.Conclusion:The levels of serum exosomes miR-552 and miR-653 are closely related to the chemotherapy efficacy of gastric cancer,and dynamic monitoring of the above indexes is helpful for the evaluation of the disease and prognosis of gastric cancer.In this study,the risk nomogram model constructed based on the above indexes and other risk factors has high predictive value and clinical practicability for chemotherapy efficacy in patients with gastric cancer.

Objective:To investigate the relationship between the expression levels of serum microRNA(miR-138-5p)and long non-coding RNA(LncRNA)NEAT1 in patients with colorectal cancer(CRC)and clinical pathological features and prognosis.Methods:Totally 163 CRC patients admitted to our hospital from May 2019 to August 2021 were used as the CRC group,and were assigned into a survival group(n=104)and a death group(n=47)based on 3-year prognosis.Another 175 patients with benign colorectal lesions were as the control group.Real-time fluorescence quantitative PCR was used to measure serum miR-138-5p and LncRNA NEAT1.K-M curve was used to analyze the relationship between serum miR-138-5p and LncRNA NEAT1 expression and prognosis of CRC.Multivariate Cox re-gression was used to analyze the influencing factors of prognosis of CRC.ROC was used to analyze the predictive value of serum miR-138-5p and LncRNA NEAT1 for prognosis of CRC.Results:Compared with the control group,the serum miR-138-5p in the CRC group was lower(t=12.802,P<0.05),and the LncRNA NEAT1 was higher(t=13.752,P<0.05).The serum miR-138-5p was related to the differentiation degree,T stage,and N stage of CRC patients(χ2=4.780,6.557,8499,P<0.05);and the serum LncRNA NEAT1 was associated with T stage and N stage in CRC patients(χ2=8.352,9.642,P<0.05).There were obvious differences between the survival group and the death group in T stage and N stage(χ2=6.801,7.580,P<0.05),and the serum miR-138-5p in the survival group was lower than that in the death group(t=8.290,P<0.05),while the serum LncRNA NEAT1 was higher than that in the death group(t=10.008,P<0.05).K-M curve showed that patients with high miR-138-5p expression had a higher 3-year survival rate than those with low miR-138-5p expression(Log Rank χ2=6.661,P=0.010);and the 3-year survival rate of patients with high ex-pression of LncRNA NEAT1 was lower than that of patients with low expression of LncRNA NEAT1(Log Rank χ2=10.620,P=0.001).Multivariate Cox regression analysis showed that T stage(HR=3.516),N stage(HR=2.983),serum miR-138-5p(HR=0.927),and LncRNA NEAT1(HR=1.659)were all factors affecting the prognosis of CRC(P<0.05).ROC results showed that the AUC for predicting poor prognosis in CRC by combining serum miR-138-5p and LncRNA NEAT1 was 0.716,which was obviously higher than that predicted by miR-138-5p(Z=3.173,P=0.002)and LncRNA NEAT1(Z=3.253,P=0.001)alone.Conclusion:Serum miR-138-5p is lower and LncRNA NEAT1 is higher in CRC pa-tients.Moreover,the levels of both are closely related to the clinical pathological features and prognosis.

Through molecular docking and experimental validation,24 SPF male KM mice were ran-domly divided into four groups:the control group(CON),model group(LPS),high-dose Yang Shuhua group(YSH-H),which was gavaged with drug solution containing 1 g/mL crude Yang Shuhua,and the low-dose Yang Shuhua group(YSH-L),which was gavaged with drug solution containing 0.5 g/mL crude Yang Shuhua for a 17-day experimental period.Mouse body weight was recorded during the experiment,and fecal scoring was done 1 h after intraperitoneal injection of LPS.At the end of the experiment,histopathological changes in the jejunum tissue were examined,and the expression of tight junction protein-related genes was detected.Compared to the CON group,mice in the LPS group showed significant decreases in villus height,villus height/crypt depth(V/C)ratio(P＜0.01),and significant increase in crypt depth(P＜0.01).The mRNA ex-pression levels of ZO-1 and claudin-1 were significantly decreased(P＜0.01).Compared to the LPS group,mice in the YSH-H group showed significant decrease in crypt depth(P＜0.05),significant increase in villus height(P＜0.05),and significant increase in V/C ratio(P＜0.01).The YSH-L group showed a significant increase in V/C ratio(P＜0.05),a trend of decreased crypt depth,and an increasing trend of villus height.The mRNA expression of ZO-1 in the YSH-H group showed a significant increase(P＜0.05)and claudin-1 showed an increasing trend.Luteolin,quercetin,kaempferol,eriodictyol,and the top 5 potential key targets TP53,IL-1β,TNF,AKT1,and IL-10 exhibited molecular docking scores less than-20.95 kJ/mol,indicating strong activity.GO and KEGG enrichment analysis suggested that Yang Shuhua compounds might act on enteritis through the TNF signaling pathway,IL-17 signaling pathway,and PI3K-Akt signaling pathway.The qPCR results showed an upward trend in the mRNA expression levels of TLR4 and AKT1,significant in-crease in Caspase-1 and ASC(P＜0.05),and significantly increased expression of NF-κB and NL-RP3(P＜0.01).The mRNA expression level of AKT1,TLR4,NLRP3,ASC,Caspase-1,and NF-κB decreased compared to the LPS group,with significant differences in Caspase-1 and NF-κB(P＜0.05).This study suggests that Yang Shuhua exerts anti-enteritis effects through multiple compo-nents and pathways,with blockade of the TLR4-AKT-NF-κB pathway possibly being a key thera-peutic mechanism for treating enteritis.