Objective:To investigate the causal effects of plasma lipidomics on pancreatitis using Mendelian ran-domization(MR)and evaluate the roles of intra-pancreatic fat deposition(IPFD)and gallstone disease in this relation-ship.Methods:A bidirectional MR analysis was conducted,with 179 plasma lipids as exposures and acute pancreati-tis(AP)and chronic pancreatitis(CP)as outcomes.Data were sourced from genome-wide association studies(GWAS),the UK Biobank,and the FinnGen project.Two-step Mendelian randomization(TSMR)and multivariable Mendelian ran-domization(MVMR)analyses were applied to assess the mediating roles of IPFD and gallstone disease in the associa-tion between plasma lipids and pancreatitis.Results:MR analysis identified two sterols negatively associated with AP(P＜0.05)and seven sterols negatively associated with CP(P＜0.05).One phospholipid showed a positive association with CP(P＜0.05).IPFD was positively associated with both AP and CP.Gallstone disease was confirmed as a risk fac-tor for AP.However,TSMR analysis indicated that neither IPFD nor gallstone disease mediated the relationship be-tween plasma lipids and pancreatitis.Conclusion:The causal relationship exists among plasma lipomics and AP/CP,also between IPFD,cholelithiasis and pancreatitis.These findings highlight novel risk factors and potential biomarkers to support early diagnosis and intervention for pancreatitis.

Objective:To investigate biomarkers that are significantly associated with the immune checkpoint(ICs)genes of colorectal cancer(CRC)and have a key impact on the prognosis of patients,and to search for related sensitive drugs by using bioinformatics methods.Methods:Genes with up-regulated expression in TCGA database and associated with poor prognosis of patients were screened,and molecules with high correlation with immune checkpoint were extracted to verify their impact on the prognosis of patients with colorectal cancer.Finally,their im-pact on immune cell infiltration and correlation were detected,and sensitive drugs that act on target genes were ana-lyzed and searched.Results:Colorectal cancer patients with up-regulated expression of tissue inhibitor of metallo-proteinase 1(TIMP1)had poor prognosis.Different TIMP1 expression levels showed significant differences in the infil-tration levels of various immune cells.Further drug sensitivity analysis predicted that bleomycin and middotolin could be highly sensitive to samples with high TIMP1 expression.Conclusion:TIMP1 is expected to be a new predictive biomarker to identify the benefits of cancer immunotherapy,and bleomycin and middotolin may be potential individualized treatment options for patients with high expression of TIMP1.

Objective:To investigate the relationship between the longitudinal trajectory of perioperative changes in TSH and recovery after microwave ablation of benign thyroid nodules.Methods:251 BTN patients admitted to our hospital from October 2021 to October 2024 were selected as the study subjects,and the group-based trajectory mod-eling(GBTM)model grouping principle was applied to determine the development trajectory of TSH levels.Multiple lin-ear regression was used to analyze the relationship between thyroid function and serum inflammatory factors before and after surgery in patients with different TSH level development trajectories;Cox regression was used to analyze the relationship between TSH level change trajectories and therapeutic efficacy and trend test was performed;binary log-binomial regression model was applied to calculate the relative risk(RR)of postoperative complication rates in different groups of patients.Results:In patients with BTN,four different trajectories of TSH level development were identified:low-stable(90 cases),low-growth(47 cases),medium-growth(63 cases),and high-growth(51 cases).There was a sta-tistically significant difference in surgical efficacy between the developmental trajectories of different TSH levels(P＜0.05),and the low-stable type had the highest apparent and overall efficacy rates,followed by the low-growth type.The postoperative and preoperative thyroid function indexes and serum inflammatory factors of patients with different TSH level development trajectories showed statistical differences(P＜0.05),the postoperative index levels of FT3 and FT4 were lower than preoperative,and the postoperative index levels of IL-8,hs-CRP,and TNF-α were higher than the preoperative ones,and the postoperative indexes of thyroid function(FT3,FT4)and serum inflammatory factors of the four groups of patients(IL-8,hs-CRP,TNF-α)showed statistically significant differences(P＜0.05).The results of multiple linear regression showed that TSH levels were negatively correlated(P＜0.05)with thyroid function indices(FT3,FT4)and positively correlated(P＜0.05)with serum inflammatory factors(IL-8,hs-CRP,TNF-α).The results of COX re-gression analysis showed that the difference in trend test was statistically significant(P＜0.001)among low-growth,medium-growth,and high-growth types,using low-stable type as a reference.The difference in the total postopera-tive complication rate among the four groups was statistically significant(P＜0.05),and the risk of total postoperative complications was elevated in patients with low-growth,medium-growth,and high-growth types compared with low-stable types(RR>1,P＜0.05).Conclusion:TSH levels were closely associated with recovery after microwave ablation of benign thyroid nodules,TSH levels were negatively correlated with FT3 and FT4,and positively correlated with IL-8,hs-CRP,and TNF-α.The low-stabilized type had the highest apparent and total efficiency,followed by the low-growth type.

Objective:To analyze the clinical and ultrasonographic characteristics of papillary thyroid carcinoma(PTC)and explore their correlation with cervical lymph node metastasis(CLNM),thereby constructing a nomogram pre-diction model for assessing the risk of CLNM in PTC.Methods:A total of 553 patients(corresponding to 553 nod-ules)with papillary thyroid carcinoma(PTC),confirmed by postoperative pathology,who underwent ultrasonography and had complete clinical data at the Second Hospital of Shandong University between December 2019 and December 2022,were included.228 patients(228 nodules)hadcervical lymph node metastasis,and 325 patients(325 nodules)were without cervical lymph node metastasis.All patients were categorized into metastasis and non-metastasis groups based on the presence or absence of cervical lymph node metastasis.These groups were then randomly di-vided into training and validation sets in a 7:3 ratio.Differences in clinical and ultrasonographic characteristics between the two groups were compared,and a nomogram was constructed.Results:Univariate analysis revealed statistically significant differences between the metastasis group and the non-metastasis group in terms of age,presence of Hashimoto's thyroiditis,multifocality,taller-than-wide shape,calcification,capsular contact,and blood flow(P<0.05).Logistic regression analysis in the training set indicated that age,presence of Hashimoto's thyroiditis,multifocality,taller-than-wide shape,calcification,and blood flow were associated with lymph node metastasis in papillary thyroid carcinoma(PTC)(P<0.05).These indicators were incorporated into a nomogram model,which demonstrated high predictive performance,good calibration,and significant clinical utility in both the training and validation sets.Conclu-sion:The nomogram prediction model,constructed based on clinical and ultrasonographic features,effectively predicts the risk of cervical lymph node metastasis(CLNM)in patients with papillary thyroid carcinoma(PTC).Patients who were older,had concomitant Hashimoto's thyroiditis,or exhibited a nodule aspect ratio≥1 were less likely to have concurrent CLNM.Conversely,patients presenting with multiple nodules,nodules with microcalcifications,or nodules demonstrating central or rich/peripheral vascularity were more likely to have concurrent CLNM.

Objective:To investigate the effect of KRAS,NRAS and BRAF gene mutations on the efficacy of pre-operative short-course radiotherapy combined with chemotherapy and postoperative liver metastasis in patients with stage Ⅱ～Ⅲ mid-low rectal cancer.Methods:The clinical data of 149 patients with stage Ⅱ～Ⅲ low rectal cancer admitted to Dongnan Hospital of Xiamen University from January 2017 to June 2020 were retrospectively analyzed.All patients received neoadjuvant therapy with preoperative short-course radiotherapy combined with chemotherapy and radical surgery,and were followed up until June 30,2023.The mutations of KRAS,NRAS and BRAF genes were de-tected by pathological tissue before surgery.The effect of neoadjuvant therapy was evaluated according to tumor re-gression grade(TRG).The risk factors of postoperative liver metastasis were analyzed by Logistic multivariate analysis.Results:There were 44 cases of KRAS,10 cases of NRAS and 12 cases of BRAF gene mutation in 149 patients with stage Ⅱ～Ⅲ low rectal cancer,and the mutation rates were 29.53%,6.71%and 8.05%.The incidence of positive vas-cular invasion in patients with KRAS gene mutation was higher than negative(P＜0.05).In NRAS mutation patients,the incidence of positive lymph node metastasis was higher than negative(P＜0.05),and the incidence of maximum tumor diameter≥5 cm was higher than that of maximum tumor diameter＜5 cm(P＜0.05).The clinical stage of BRAF muta-tion was higher in stage Ⅲ than in stage Ⅱ(P＜0.05),and the incidence of positive lymph node metastasis was higher than negative(P＜0.05).During the follow-up period,liver metastasis occurred in 42 patients,and the liver metastasis rate was 28.18%.The KRAS,NRAS and BRAF gene mutations in the effective group were 25.81%,2.15%and 3.23%,lower than those in the ineffective group(35.71%,14.29%and 17.07%,P＜0.05).Multiple factors found clinical stage Ⅲ(OR=10.620,95%CI:2.645～22.575),lymph node metastasis was positive(OR=8.774,95%CI:1.878～19.645),neoadju-vant therapy failed(OR=3.373,95%CI:1.014～11.218),KRAS gene mutation(OR=6.245,95%CI:1.876～20.789),BRAF gene mutation(OR=9.497,95%CI:1.754～19.335)were independent risk factors for postoperative liver metastasis of stage Ⅱ～Ⅲ mid-low rectal cancer.Conclusion:Mutations in the KRAS and BRAF genes of middle are associated with poorer efficacy of neoadjuvant therapy in patients with stage Ⅱ～Ⅲ mid-low rectal cancer and are also indepen-dent risk factors for postoperative liver metastasis.

Objective:To analyze the influencing factors of postoperative intestinal adhesion in patients undergoing laparoscopic cholecystectomy(LC),and to construct a nomogram prediction model based on this.Methods:A total of 265 patients who underwent LC in our hospital from November 2021 to March 2025 were retrospectively selected and randomly divided into a training set(185 cases)and a validation set(80 cases)according to the ratio of 7∶3.According to the presence or absence of postoperative intestinal adhesion,185 patients in the training set were divided into occur-rence group(28 cases)and non-occurrence group(157 cases).In the validation set,13 cases occurred and 67 cases did not occur.The clinical data of patients were collected to analyze the influencing factors of postoperative intestinal adhe-sion,and a nomogram model was constructed based on this.The receiver operating characteristic(ROC)curve was used to analyze the predictive efficacy of the prediction model on the risk of postoperative intestinal adhesion.Decision curve analysis(DCA)was used to analyze the clinical benefit of the prediction model.Result:The proportion of patients aged≥65 years,complicated with diabetes,indwelling drainage tube,residual abdominal infection,and WBC level in the occurrence group were higher than those in the non-occurrence group(P<0.05).Logistic regression analysis showed that age(OR=3.025,95%CI:1.453-6.296),diabetes(OR=3.836,95%CI:1.557-9.450),indwelling drainage tube(OR=5.312,95%CI:1.898-14.864)and residual abdominal infection(OR=6.174,95%CI:2.914-13.079)were independent influencing factors for postoperative intestinal adhesion(P<0.05).The corresponding risk rate of the nomogram model based on Logistic results ranged from 0.10 to 0.80,and the C-index was 0.842(95%CI:0.765-0.919).The calibration curve of predicting postoperative intestinal adhesion was close to the ideal curve(P>0.05).The ROC of the training set showed that the sensitivity and specificity of the model in predicting postoperative intestinal adhesion were 85.70%and 88.50%,respectively,and the area under the curve(AUC)was 0.882(P<0.05).In the validation set,the sensitivity,speci-ficity and AUC of ROC curve were 81.30%,84.10%and 0.860(P<0.05),respectively.DCA curve showed that the pre-diction model could obtain the maximum clinical benefit at the threshold probability of 0-0.23.Conclusion:The pre-diction model based on age,diabetes,indwelling drainage tube and residual abdominal infection has a good predictive value for the risk of intestinal adhesion after LC.

Objective:To explore the impacts of remimazolam(REM)on the proliferation,migration,and invasion of hepatocellular carcinoma cells by regulating sphingosine kinase 1/sphingosine 1-phosphate/sphingosine 1-phosphate receptor 3(SPHK1/S1P/S1PR3)signaling pathway.Methods:Human hepatocellular carcinoma cell line HepG2 was treated with REM at concentrations of 0,20,40,80,160,and 320 μmol/L respectively.Cell survival rate was measured,and drug concentrations were screened.Based on the results of cell survival rate,the logarithmic phase cells were di-vided into five groups:Control group,low,medium,and high concentrations of remifentanil groups(REM-L,REM-M,REM-H groups;20,40 and 80 μmol/L),and high concentrations of remifentanil+SPHK1 activator group(REM-H+K6PC-5 group).MTT assay was used to detect the survival rate of HepG2 cells.Plate cloning experiment was performed to de-tect cell proliferation ability.Scratch experiment was performed to detect cell migration ability.Transwell chamber method was performed to detect cell invasion ability.Flow cytometry was used to detect cell apoptosis.Western blot was used to detect the SPHK1,S1P,S1PR3,Bax,and Bcl-2 proteins in cells.Results:For the Control group,the REM-L,REM-M,and REM-H groups showed that the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins gradually decreased with increasing REM concentration,while the apoptosis rate and Bax,E-cadherin proteins showed an opposite trend(P<0.05).For the REM-H group,the REM-H+K6PC-5 group showed a clear increase in the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins,and a clear decrease in the apoptosis rate and Bax,E-cadherin proteins(P<0.05).Conclusion:REM may inhibit the proliferation,migration,and invasion of hepatocellular carcinoma cells and promote cell apoptosis by suppressing SPHK1/S1P/S1PR3 signaling pathway.

Objective:To explore the influence of different time intervals after stent implantation on the efficacy and prognosis of elective surgery in patients with malignant obstructive colorectal cancer(MOCRC).Methods:A total of 182 MOCRC patients were enrolled,including 92 who underwent emergency surgery(ES group)and 90 who received elective surgery after stent placement(SEMS group).The SEMS group was further divided into three subgroups based on the interval between stent placement and surgery:<11 d(n=27),11-17 d(n=39),and>17 d(n=24).Kaplan-Meier analysis was used to compare overall survival(OS)and disease-free survival(DFS),and Cox proportional hazards re-gression was employed to identify prognostic factors.Prognostic models based on surgical timing were constructed,and receiver operating characteristic(ROC)curves were drawn with area under the curve(AUC)calculated to assess model discrimination.A total of 182 patients with MOCRC were included.Among them,92 underwent emergency sur-gery(ES group),and 90 underwent elective surgery after stent implantation(SEMS group).The SEMS group was di-vided into the<11 d group(n=27),the 11-17 d group(n=39),and the>17 d group(n=24)according to the operation interval.Overall survival(OS)and disease-free survival(DFS)were compared using the Kaplan-Meier method,and prognostic factors were analyzed by Cox regression.Result:Compared with the ES group,the SEMS group had a higher rate of laparoscopic surgery and significantly less intraoperative blood loss(P<0.05),with no significant differ-ences in postoperative complication rate,stoma formation rate(P>0.05).Among SEMS patients,the 11～17 d group had the shortest hospital stay and the lowest complication rate(7.69%).Multivariate Cox analysis showed that surgery performed 11-17 d group significantly reduced the risk of death compared to emergency surgery(HR=0.650,P=0.034),while surgery 11 d group significantly increased the risk(HR=2.051,P=0.042).Independent predictors of OS in-cluded age(HR=1.060,P<0.001),preoperative CEA level(HR=1.323,P=0.002),tumor size(HR=1.421,P=0.028),tumor differentiation(HR=1.123,P=0.005),and venous invasion(HR=2.792,P<0.001).For DFS,age,tumor size,venous inva-sion,and perineural invasion were identified as independent risk factors(P<0.05),while surgical timing showed no sig-nificant association(P>0.05).Kaplan-Meier analysis revealed no significant difference in OS among different groups in stage Ⅰ-Ⅱ patients,whereas in stage Ⅲ patients,the 11-17 d group had better OS,and the>17 d group had signifi-cantly worse DFS than other groups(P=0.017).ROC curve analysis showed that the AUCs for OS prediction were 0.636(<11 d),0.601(11-17 d),and 0.750(>17 d);and for DFS prediction were 0.655,0.567,and 0.874,respectively,indicating that surgical timing has moderate discriminative value for survival outcomes.Conclusion:Elective surgery performed 11 to 17 d after stent placement can reduce mortality and improve postoperative recovery,although it has no significant impact on recurrence risk.Venous and peripheral nerve invasion are major factors affecting disease-free survival(DFS);therefore,clinical management should focus on identifying high-risk patients and optimizing individual-ized treatment strategies.

Objective:This study aimed was to analyze the disease progression of postoperative recurrence/me-tastasis of pancreatic ductal adenocarcinoma(PDAC)and provide clinical evidence for evaluating the difference in prog-nosis between site and pattern of recurrence/metastasis.Methods:The clinical data of 167 patients with PDAC who underwent pancreatectomy in Panjin Liao-Oil Gem Flower Hospital from January 2011 to June 2019 were retrospec-tively analyzed.Kaplan-Meier curves and Cox-regression analyses were applied to assess survival outcomes.Results:In this study,96 patients(57.5%)recurred within 12 months after surgery,and the median recurrence time was 10.9 months.Compared to patients without recurrence,patients with recurrence/metastasis had higher baseline CA19-9>100 IU/mL and were treated more often with neoadjuvant chemotherapy(P<0.05).In the no recurrence group,patients had histopathological analyses yielded lower less poorly differentiated tumors,less positive margin,less pT3+4 stages and pN1+2 stages(P<0.05).In a multivariate Cox regression analysis,receipt of neoadjuvant chemotherapy,poor tumor differ-entiation and positive margin were independent predictors for recurrence/metastasis within 12 months after surgery(P<0.05).Neoadjuvant treated patients had less pT1+2 stages(P=0.015),a lower lymph node ratio,less perineural invasion,less positive margin,and were less likely to be treated with adjuvant chemotherapy compared to upfront surgery treated patients(P<0.05).Recurrence/metastasis rates were higher in the neoadjuvant treated cohort versus the upfront surgery cohort(P=0.014).There was no statistical difference in the recurrence/metastasis rate distribution between neoadjuvant therapy and upfront surgery,and neoadjuvant therapy exhibited no significant impact on recurrence/metastasis patterns in PDAC(P>0.05).The overall survival period of patients without recurrence/metastasis within 12 months was signifi-cantly longer than that of patients with recurrence/metastasis after PDAC resection(P<0.001).Conclusion:The varying site recurrence/metastasis rates and time to recurrence/metastasis,underline the inherent heterogeneity of PDAC and the specific interactions in the tumor microenvironments at the recurrence/metastasis sites.Further research is essential to establish optimal personalized treatment strategies for patients with recurrent PDAC.

Objective:To investigate the expression of Neurexophilin 4(NXPH4)in hepatocellular carcinoma(HCC)and its clinical significance and function.Methods:Retrieved LIHC project data(mRNA expression profiles and clinical records)from TCGA,analyzed differential NXPH4 expression in HCC versus adjacent non-tumor tissues,and investi-gated correlations between NXPH4 expression and clinicopathological characteristics/prognostic outcomes in HCC.Using GOEA and GSEA to investigate potential biological functions of NXPH4 in hepatocellular carcinoma.Results:NXPH4 exhibited significant upregulation in 23 cancer types(P<0.05),with significant associations to advanced HCC progression markers including TNM stage(P<0.05),histologic grade(P<0.05),and vascular invasion(P<0.05).Clinically,elevated NXPH4 expression correlated with reduced OS(HR=1.64,95%CI:1.15-2.33,P=0.006)and DSS(HR=1.88,95%CI:1.19-2.96,P=0.007).The immune infiltration results showed that NXPH4 expression was significantly correlated with Th2 cells and Th17 cells(all P values<0.05).Furthermore,NXPH4 expression was positively correlated with the levels of several immune checkpoint markers:TIGIT(r=0.265),PD-1(r=0.297),CTLA-4(r=0.302),and LAG-3(r=0.179,all P<0.001).Gene enrichment analysis revealed NXPH4 was significantly enriched in:pattern specification process(P<0.001);receptor ligand activity(P<0.001);collagen formation(P=0.009);activation of matrix metalloproteinases(P<0.001);neuro-active ligand receptor interactions(P<0.001);and ALK2 signaling(P=0.039).Conclusion:NXPH4 is associated with clinical pathological staging and poor prognosis in HCC patients;NXPH4 is associated with oncogenic pathways and im-mune infiltration,and has high value in predicting patient prognosis and immunotherapy.