Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Background::Thyroid cancer (TC) is the most common malignancy of the endocrine system. This study aimed to assess the global distribution of TC incidence and mortality in 2022, as well as to predict the burden for the year 2050.Methods::Data from the GLOBOCAN 2022 database were used to analyze the age-standardized incidence and mortality rates of TC by sex, age group (<55 years and ≥55 years), country, world region, and level of Human Development Index (HDI) for 185 countries. The predicted incidence and mortality burden for 2050 was calculated based on demographic projections.Results::In 2022, an estimated 821,214 new TC cases and 47,507 TC-related deaths occurred worldwide. The age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were higher in women (ASIR: 13.60 per 100,000; ASMR: 0.53 per 100,000) than in men (ASIR: 4.60 per 100,000; ASMR: 0.35 per 100,000). The ASIR in high HDI countries was approximately ten times higher than that in low HDI countries for both sexes, with relatively similar ASMR across regions. Among 185 countries, China had the largest number of TC cases (accounting for 56.77% of total cases) and TC-related deaths (accounting for 24.35% of global TC-related deaths), with the highest ASIR in men (13.30 per 100,000). Worldwide, approximately 64.63% of TC cases occurred in populations under 55 years old, while nearly 82.99% of TC-related deaths occurred in populations aged 55 years and above. If the rates stay the same as in 2022, it is projected that approximately 1,100,000 new TC cases and 91,000 TC-related deaths will occur in 2050, indicating a 34.15% and 89.58% increase, respectively.Conclusions::TC is a highly frequent cancer worldwide with disparities across regions, genders, and age groups. Our results provide light on the worldwide TC disease burden and facilitate regionally customized prevention measures.

Objective To investigate the risk factors for delayed union of extra-articular fractures of the middle and lower third of the tibia treated by locking plate.Methods Total of 135 patients of extra-articular fractures of the middle and lower third of the tibia from January 2013 to December 2018 were retrospectively analyzed,including 85 males and 50 females,ranged from 19 to 80 years old.All cases were treated with locking plates.The patients were divided into union group and delayed union group ac-cording to the condition of fracture union.The risk factors of delayed healing were determined by univariate analysis of 14 factors that might affect fracture healing first,then the factors with significance were analyzed by binary Logistic regression.Results There were 13 patients of delayed union,and the rate of delayed union was 9.63％.Univariate analysis showed that delayed union was associated with age,smoking,reduction method,anemia and time of preoperative preparation.Regression analysis showed thatage[OR=0.849,95％CI(0.755,0.954),P=0.006],smoking[OR=0.020,95％CI(0.002,0.193),P=0.001],reduction method[OR=23.924,95％CI(2.210,258.943),P=0.009],anemia[OR=0.016,95％CI(0.001,0.289),P=0.005]were the con-tributory factors for delayed union.Conclusion Young age,smoking,closed reduction and anemia are the risk factors for de-layed union of extra-articular fractures of the middle and lower third of the tibia treated by locking plate.

Objective To explore the risk factors of early femoral head necrosis in patients with femoral neck fracture after operation,and to establish a nomogram prediction model.Methods A total of 167 patients with femoral neck fracture from Jan-uary 2020 to April 2022 were selected and divided into necrosis group and non-necrosis group according to whether femoral head necrosis occurred in the early postoperative period.There were 21 males and 17 females in the necrosis group,aged from 33 to 72 years old,with an average of(53.49±10.96)years old,and the time from injury to operation ranged from 40 to 67 hours,with average time of(53.46±7.23)hours.There were 72 males and 57 females in the non-necrosis group,aged from 18 to 83 years,with an average of(52.78±12.55)years old,and the time from injury to operation was 18 to 65 hours,with an aver-age time of(39.88±7.79)hours.The potential influencing factors,including patient gender,diabetes mellitus,hypertension,chronic liver disease,posterior inclination angle of the femoral head,operation mode,fracture displacement,fracture line loca-tion,preoperative braking traction,screw arrangement mode,reduction quality,age,body mass index(BMI),and injury to operation time were subjected to single factor analysis.Logistic multivariate regression analysis was conducted for factors with a significance level of P＜0.05.Results The incidence of femoral head necrosis in 167 patients with femoral neck fracture was 22.76％.The following factors were identified as independent risk factors for early postoperative femoral head necrosis in pa-tients with femoral neck fractures:coexisting diabetes[OR=5.139,95％CI(1.405,18.793),P=0.013],displaced fracture[OR=3.723,95％CI(1.105,12.541),P=0.034],preoperative immobilization[OR=3.444,95％CI(1.038,11.427),P=0.043],quality of reduction[OR=3.524,95％CI(1.676,7.411),P=0.001],and time from injury to surgery[OR=1.270,95％CI(1.154,1.399),P=0.000].The Hosmer-Lemeshow goodness-of-fit test(x2=3.951,P=0.862),the area under the receiver operator characteristic(ROC)curve was 0.944[P＜0.001,95％CI(0.903,0.987)],with a sensitivity of 89.50％,the specificity was 88.40％,the maxi-mum Youden index was 0.779,and the overall trend of the model correction curve was close to the ideal curve.Model regres-sion equation was Z=1.637 × diabetes+1.314× fracture displacement+1.237 × preoperative braking traction+1.260 × reduc-tion quality+0.239 ×injury to operation time-18.310.Conclusion The occurrence of early femoral head necrosis in patients with femoral neck fracture postoperatively is affected by multiple factors.The risk early warning model established according to the factors has good predictive efficacy.

Background and Aims:There is currently no consensus on whether the pancreaticoduodenectomy with Heidelberg triangle operation(PDTRIANGLE)or the standard radical pancreaticoduodenectomy(PDSTANDARD)is more beneficial for patients with pancreatic cancer,and no large-scale multicenter studies have confirmed this.Therefore,this study was conducted to compare the clinical efficacy and safety of PDTRIANGLE and PDSTANDARD for treating pancreatic cancer through a Meta-analysis. Methods:Relevant literature comparing the two surgical approaches comparing the two surgical approaches for treating pancreatic cancer was screened from Chinese and English databases based on inclusion criteria.The search timeframe extended from the inception of the databases to May 2024,and Review Manager 5.3 software was used for Meta-analysis of the extracted outcome variables. Results:A total of 6 retrospective studies were included,comprising 658 patients,with 315 in the PDTRIANGLE group and 343 in the PDSTANDARD group.The Meta-analysis results showed that the operative time in the PDTRIANGLE group was longer than that in the PDSTANDARD group(OR=1.52,95％CI=0.42-2.61,P=0.007),the lymph node dissection rate was higher in the PDTRIANGLE group(OR=0.70,95％CI=-0.4-1.01,P＜0.000 01),and the R0 resection rate was also higher in the PDTRIANGLE group(OR=1.63,95％CI=1.03-2.58,P=0.04).The incidence rates of postoperative lymphatic fistula and diarrhea were higher in the PDTRIANGLE group compared to the PDSTANDARD group(OR=5.60,95％CI=1.81-17.29,P=0.003;OR=0.13,95％CI=0.07-0.20,P＜0.000 1).The length of hospital stay was longer in the PDTRIANGLE group(OR=0.40;95％CI=-0.14-0.65,P=0.003).The overall survival rates at 1 and 2 years were significantly better in the PDTRIANGLE group compared to the PDSTANDARD group(OR=2.19,95％CI=-1.27-3.76,P=0.005;OR=1.65,95％CI=-1.01-2.67,P=0.04),and the 1-year disease-free survival rate was also significantly higher in the PDTRIANGLE group(OR=3.71,95％CI=2.27-6.07,P＜0.000 01),although the difference in the 2-year disease-free survival rate between the two groups was not statistically significant(OR=2.63,95％CI=-0.91-7.59,P=0.07). Conclusion:PDTRIANGLE is a safe and effective treatment for pancreatic cancer.Compared to PDSTANDARD,PDTRIANGLE significantly improves the R0 resection rate,thereby enhancing the postoperative disease-free survival rate and achieving a better long-term prognosis.

Brucellosis,a worldwide epidemic bacterial zoonotic infectious disease caused by bacteria of the genus Brucella,jeopardizes livestock production and poses a major threat to public health safety.Among the various components of Brucella,the outer membrane proteins play crucial roles as the primary immune and protective antigens.These proteins are closely asso-ciated with Brucella's virulence,regulation of the immune response,and ability to survive and multiply within host cells.This article summarizes recent research progress in the primary outer membrane proteins of Brucella,and offers a synthesized view of the current knowledge landscape.Understanding the antigenic characteristics of Brucella outer membrane proteins may sub-stantially contribute to the establishment of new diagnostic methods and the design of new vaccines,thus potentially leading to more effective prevention strategies against brucellosis.The review provides a reference for future studies and may aid in brucel-losis control efforts.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

Objective:To investigate the effects of CP-31398 on proliferation and metastasis of gallbladder carcinoma cell lines expressing mutant P53GBC-SD and wild-type p53NOZ.Meth-ods:The effects of CP-31398 on the proliferation of wild-type and mutant p53 gallbladder carci-noma cells were detected by CCK8 cell proliferation assay and clonal formation assay.The effect of CP-31398 on cell cycle and apoptosis of gallbladder carcinoma was detected by flow cytometry.The effects of CP-31398 on the migration and invasion of gallbladder carcinoma cells were detected by scratch,cytoskeleton and Transwell assay.The effect of CP-31398 on the expression of p53 protein was detected by Western blot and the related mechanism was discussed.Results:In mutant P53GBC-SD cells,the proliferation of CCK8 cells showed that the proliferation rate of gallbladder cancer cells in CP-31398 treatment group was slower than that in control group(P＜0.01).The cycle experiment showed that compared with the control group,the proportion of cells in S phase in-creased in CP-31398 treatment group,and the proportion of cells in G0 and G1 phase decreased,so the cells were blocked in S phase(P＜0.001).Apoptosis experiment showed that the apoptosis rate of control group was lower than CP-31398 treatment group(P＜0.05).Transwell experiment showed that the number of cells passing through the cell compartment in the control group was higher than that in the CP-31398 treatment group.Western blot analysis showed that the expression of p53 pro-tein in CP-31398 treatment group was increased(P＜0.05).In wild-type p53NOZ cells,the prolifera-tion of CCK8 cells showed that the proliferation rate of gallbladder cancer cells in CP-31398 treat-ment group was slower than that in control group.The number of cell clones in the control group was higher than that in the CP-31398 treatment group(P＜0.001).The cycle test showed that the propor-tion of cells in G2 and M phases increased significantly,while the proportion of cells in G0 and G1 phases decreased,and the cells were blocked in G2 and M phases(P＜0.001).Apoptosis experiment showed that the apoptosis rate of control group was(14.04±3.08)％,and that of CP-31398 treat-ment group was(34.55±3.30)％(P＜0.01).Transwell experiment showed that the number of cells passing through the cell compartment in the control group was higher than that in the CP-31398 treatment group.Western blot analysis showed that the expression of p53 protein in CP-31398 treatment group was increased(P＜0.01).Conclusion:CP-31398 can effectively inhibit the prolif-eration and metastasis of gallbladder cancer cells,and is independent of p53 mutation,and CP-31398 has a good effect on NOZ gallbladder cancer cell lines expressing wild-type p53,which can be used as a new drug treatment for gallbladder cancer.

Prostate cancer(PCa)ranks as the second most prevalent malignancy among males worldwide at present,and its prevalence keeps rising.Focal therapy not only results in tumor necrosis but also encourages the release of autoantigens originating from the tumor into the bloodstream and activates the host immune system to effectively fight the tumor.However,focal therapy alone may not achieve the total ablation of cancer cells and may cause locoregional recurrence.Immunotherapy,by boosting the body's immune re-sponse,destroys tumor cells and prevents immune escape.Recent studies show that focal therapy combined with immunotherapy can produce a better clinical efficacy by enhancing the initial immune response,especially for low-to intermediate-risk confined PCa.This article offers some fresh perspectives on the management of PCa by reviewing the etiology and progression of the malignancy,focal ther-apeutic options,and advantages and vista of focal therapy combined with immunotherapy.

Objective To explore the correlation between colorectal cancer tissue Janus kinase 2(JAK2)gene mutations and T cytokine 3(TCF3)protein expression with clinical pathological characteristics and prognosis,and to provide laboratory reference indicators for early evaluation of the illness severity and prognosis of colorectal cancer.Methods A retrospective analysis was conducted on the data of 50 colorectal cancer patients who were admitted from January 2016 to April 2021 and retained colon cancer and adjacent tissue wax blocks.Basic information,clinical and pathological features such as TNM staging,lymph node metastasis,and 3-year survival prognosis of the patients were collected.The wax blocks of colon cancer and adjacent tissues of patients were detected,in which Taqman fluorescence probe method was applied to detect the distribution of JAK2 gene at the rs2230724 locus AA,AG,and GG genotypes in colon cancer tissues,and immunohistochemistry method was applied to detect the positive expression rate of TCF3 protein in colon cancer and adjacent tissues.The basic information,JAK2 rs2230724 gene mutation,and TCF3 protein expression of patients with different clinical and pathological characteristics were compared,and the influencing factors of clinical and pathological characteristics of colon cancer was analyzed by logistic regression model.Kaplan Meier survival curve was applied to compare the survival prognosis of patients with JAK2 gene mutations and TCF3 protein expression in colorectal cancer tissue,and Cox regression model was applied to analyze the risk factors affecting the prognosis of colorectal cancer patients.Results The positive expression rate of TCF3 protein in colon cancer tissues was higher than that in adjacent tissues(P＜0.05).The age,BMI,proportion of GG genotype at rs2230724 locus of JAK2 gene and positive expression rate of TCF3 protein in TNM stage Ⅲ colon cancer patients were higher than those in TNM stage Ⅰ-Ⅱ patients(P＜0.05);The age,BMI,smoking rate,proportion of GG type at the rs2230724 locus of JAK2 gene in colon cancer tissue,and positive expression rate of TCF3 protein in patients with lymph node metastasis were higher than those without lymph node metastasis(P＜0.05);The results of the logistic regression model analysis showed that the influencing factors of clinical pathological features such as TNM staging and lymph node metastasis in colon cancer were age,mutation of JAK2 gene rs2230724 site in colon cancer tissue,and positive expression rate of TCF3 protein(P＜0.05).The Kaplan Meier survival curve analysis showed that patients with JAK2 gene rs2230724 GG genotype and TCF3 protein positivity in colon cancer tissue had higher cumulative all-cause mortality rates(P＜0.05).The results of univariate and multivariate Cox regression model analysis showed that independent risk factors affecting the prognosis of colorectal cancer patients include JAK2 gene rs2230724 site GG type,TCF3 protein positive expression,TNM stage Ⅲ,lymph node metastasis,and age.Conclusion The proportion of JAK2 gene rs2230724 GG type and TCF3 protein expression in colorectal cancer tissues are related to their clinical pathological characteristics and prognosis,and can be used as reference indicators for evaluating clinical pathological characteristics and predicting prognosis of colorectal cancer.