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 systematically evaluate the molecular characteristics and prognostic value of ammonia death-related genes in hepatocellular carcinoma(HCC).Methods:Consensus unsupervised clustering was used to identify ammonia death-related molecular subtypes in HCC samples.Weighted gene co-expression network analysis(WGCNA)was applied to identify gene modules associated with ammonia death.Support vector machine(SVM)and LASSO algorithms were used to screen four hub genes,and a risk score system was constructed based on a LASSO-Cox regression model.The association between the risk model and patient survival,tumor microenvironment,and re-sponse to immunotherapy was further analyzed.Results:Consensus clustering identified two distinct ammonia death-related molecular subtypes(P<0.05).The constructed risk score model showed good predictive performance for overall survival in HCC patients and was closely associated with immune infiltration characteristics of the tumor microenviron-ment and immunotherapy responsiveness(P<0.05).Conclusion:The ammonia death-related risk score model may serve as a novel prognostic biomarker for HCC and provide potential guidance for immunotherapy strategies.

Objective:To explore the potential prognostic value of the HAMP(hepcidin)gene in gastric adenocarci-noma and its correlation with immune infiltration in gastric cancer.Methods:This study systematically analyzed the ex-pression characteristics of the HAMP gene using bioinformatics approaches based on mRNA data from 448 gastric ad-enocarcinoma tissues and non-tumor tissues in the TCGA database.Firstly,the cBioPortal platform was employed to analyze the genetic variation features of the HAMP gene,and the LinkedOmics database was used to evaluate the corre-lation between its methylation status and expression levels.Kaplan-Meier survival analysis with log-rank test was per-formed to assess the relationship between HAMP expression levels and patient prognosis.Furthermore,by integrating TIMER2.0 and TISIDB databases,we systematically evaluated the correlation between HAMP expression and immune-related genes as well as immune cell infiltration.Gene Set Enrichment Analysis(GSEA)was conducted to investigate HAMP-associated signaling pathway characteristics.Finally,STRING and Gepia databases were utilized to construct a protein-protein interaction network of HAMP and identify core interacting genes,comprehensively evaluating the role of HAMP in immune infiltration in gastric adenocarcinoma.Results:The expression level of HAMP was significantly higher in gastric adenocarcinoma tissues compared to normal tissues(P<0.01),and its elevated expression was strongly associ-ated with poor patient prognosis,manifested by significantly shorter overall survival(OS),progression-free survival(PFS),and post-progression survival(PPS)(all P<0.05).Genomic analysis revealed that HAMP mutations in gastric cancer were predominantly amplification-type,and its methylation level showed a positive correlation with mRNA expression(r=0.14,P<0.001).Immunological analysis demonstrated that high HAMP expression was significantly correlated with multiple key immune checkpoint molecules(PD-1:rho=0.274;PD-L1:rho=0.211;CTLA-4:rho=0.199,all P<0.001)and immune cell infiltration(dendritic cells:r=0.548;macrophages:r=0.414;neutrophils:r=0.374,all P<0.001).Pathway enrichment analy-sis indicated that the high HAMP expression group was significantly enriched in immune-related pathways including anti-gen presentation and NK cell-mediated cytotoxicity.Furthermore,protein-protein interaction network analysis identified core interacting genes such as TREM2 and TYROBP,suggesting that HAMP may participate in tumor immune regulation through specific molecular networks.Conclusion:HAMP is highly expressed in gastric cancer,and its high expression significantly reduces the survival time of gastric adenocarcinoma patients,demonstrating prognostic value.HAMP ex-pression is positively correlated with most immune-related genes in STAD and significantly associated with the abun-dance of multiple immune cell infiltration levels,serving as an independent prognostic factor related to immune infiltration.

Objective:To investigate the feasibility of daily laparoscopic appendectomy for acute appendicitis in college students and establish a predictive model of the nomogram.Methods:A prospective analysis was performed on 82 college students with acute appendicitis who were admitted to hospital continuously from December 2023 to De-cember 2024.All patients received laparoscopic appendectomy and accelerated rehabilitation surgical measures combin-ing traditional Chinese and Western medicine,and were divided into two groups according to whether the daytime op-eration mode was achieved.Multivariate Logistic regression analysis was used to screen the independent influencing factors for achieving the day surgery model,and the prediction model was constructed,evaluated and verified.Results:Of the 82 patients,46(56%)achieved the daytime operation mode,the mean length of hospitalization was(41.37±6.33)h,and no serious complications were observed 30 days after surgery.The independent influencing factors for achieving this model were CRP≤13.9 mg/L,abdominal pain time≤22 h,appendix diameter≤10 mm,no drainage tube placed,and postoperative VAS score≤2.5(all P<0.05).The area under the curve of the prediction model was 0.905(95%CI:0.845～0.966),and the calibration chart indicated that the predicted probability of the model was in good agreement with the ac-tual probability,and the decision curve showed good clinical benefit.Conclusion:It is safe and feasible for college stu-dents to receive day surgery mode of laparoscopic appendectomy.The created nomogram model has good predictive ability,which can identify eligible patients as early as possible,and take timely intervention measures to improve the achievement rate.

Objective:To investigate the impacts of preoperative regional arterial infusion chemotherapy(PRAC)combined with laparoscopic surgery on the efficacy,safety,immune function,and serum levels of matrix metallopro-teinase-7(MMP-7)and human cartilage glycoprotein(YKL-40)in patients with colorectal cancer.Methods:This study retrospectively selected 164 patients with colorectal cancer(January 2014 to December 2016)as the research subjects.Patients who underwent conventional treatment and laparoscopic surgery were included into control group(81 cases);patients undergoing PRAC+laparoscopic surgery were included into observation group(83 cases).The clinical efficacy,stress response indicators,immune function related indicators,changes in serum MMP-7 and YKL-40 levels,and occurrence of adverse reactions in two groups were observed before treatment(T0)and after 4 cycles of chemotherapy(T1).Results:At T1,the total effective rate of observation group(85.54%)was greatly higher than that of control group(67.90%)(P<0.05).The levels of cortisol(Cor),neutrophile granulocyte(NE),white blood cell count(WBC),and interleukin(IL)-6 were prominently increased in both groups(P<0.05),but the levels of these indicators in observation group were greatly lower than those in control group(P<0.05).The levels of IgM and IgA in both groups were greatly reduced(P<0.05),but the levels of IgM and IgA in observation group were prominently higher than those in control group(P<0.05).The levels of MMP-7 and YKL-40 decreased in both groups(P<0.05),and the level in observation group was prominently lower than that in control group(P<0.05).There was no significant difference in the overall incidence of adverse reactions and 5-year survival rate between control group and observation group(P>0.05).Conclusion:The combination of PRAC and laparoscopic surgery has prominent healing effects and certain safety in patients with colorectal cancer.It can effectively improve immune function,reduce serum MMP-7 and YKL-40 levels.

Objective:The current study was designed to elucidate the expression pattern,prognosis value,im-mune characteristics and potential molecular mechanisms of HDGF in HCC.Methods:Clinical and gene expression data of the TCGA-LIHC cohort were collected.The Kaplan-Meier method,time-dependent receiver operating charac-teristic(ROC)curves and Cox regression analysis were used to analyze the prognostic value of HDGF.The expression level difference of HDGF was analyzed using the R package DESeq2.Gene ontology,KEGG and GSEA analyses were used to determine the biological function of HDGF in HCC development.The SsGSEA method were used to analyze the immune infiltrates of HCC.Human methylation 450 data and level 3 HTSeq-FPKM data from TCGA-LIHC were used to analyze the effects of DNA methylation level on HDGF expression.Results:Our results indicated that HDGF was over-expressed in HCC and correlated with historical grade and AFP levels(P<0.001).HDGF expression level is an indepen-dent risk factor for overall survival in patients with HCC(P=0.008).The functional and immune analysis indicated that HDGF is closely related to tumor-immune microenvironment and immune infiltration,especially Cytotoxic cells,pDC and Th2 cells(P<0.001).In addition,high HDGF expression in HCC was associated with demethylation of its promoter region(P<0.05).Conclusion:Our results demonstrated that HDGF independently predicts unfavorable prognosis and regu-lates the immune microenvironment of HCC,suggesting HDGF as a potential immunotherapeutic target for HCC.