ObjectiveTo investigate the expression level of mammalian sterile 20-like kinase 1 （MST1） in prostate cancer （PCa） tissues， its biological functions， and its regulatory effects on androgen receptor （AR） and vascular endothelial growth factor （VEGF） expression. MethodsImmunohistochemistry was performed to detect MST1 expression in 77 prostate cancer tissues and 34 benign prostatic hyperplasia （BPH） tissues， and the relationship between MST1 expression and clinicopathological parameters was analyzed. MST1-overexpressing C4-2 and LNCaP cell lines were constructed. CCK-8 assay， Transwell migration assay， and angiogenesis assay were conducted to evaluate the effects of MST1 on cell proliferation， migration， and angiogenesis. The expression changes of AR and VEGF were detected by qRT-PCR and Western blot. ResultsMST1 expression was significantly lower in PCa tissues compared with BPH tissues （P=0.012）. Low MST1 expression was significantly associated with tumor metastasis （P=0.033）. MST1 overexpression inhibited C4-2 cell proliferation and migration， with transmembrane migrated cells reduced by 53.6% （P<0.01）. MST1 overexpression decreased the mRNA and protein expression levels of AR and VEGF （P<0.05）. Angiogenesis assay demonstrated that the length of new vessel structure was significantly reduced （P<0.05）. ConclusionMST1 shows a low expression level in PCa tissues and is associated with tumor metastasis. MST1 exerts tumor-suppressive effects in prostate cancer by inhibiting cell proliferation， migration， and angiogenesis， as well as downregulating the expression of AR and VEGF， indicating its potential as a therapeutic target for prostate cancer.

Objective To analyze the characteristics of death cases in a certain tertiary hospital,providing references for hospital management decisions and the evaluation of the effectiveness of medical services.Methods The information of death ca-ses of inpatients in the hospital from 2019 to 2023 was extracted through the inpatient medical records information system,and the medical records of inpatients were retrospectively analyzed by clinical epidemiological methods.Results The cumulative number of inpatients admitted to the hospital from 2019-2023 was 459 821,with 3 250 deaths and a case-fatality rate of 0.71％.There was a decreasing trend in the case fatality rate from 0.71％in 2019 to 0.63％in 2023,but the difference was not statistically significant(APC=-3.17,P＞0.05).The case fatality rate was 0.97％for males and 0.45％for females,with males having a higher case fatality rate than females(x2=435.206,P＜0.05).The mean age of the deceased cases was(69.59±17.70)years,and the case fatality rate increased gradually with age,and the highest case fatality rate was 2.98％in the age group of ≥80 years.The difference in case fatality rate between patients of different age groups was statistically significant(x2=3 502.991,P＜0.05).The top 5 causes of death of hospitalized patients were tumor,circulatory diseases,respiratory diseases,some infec-tious and parasitic diseases and injuries,poisoning and external causes,accounting for 87.33％of the total deaths.The main causes of death in neoplasms were bronchial and pulmonary malignancies,hepatic and intrahepatic biliary malignancies,and gas-tric malignancies;in the circulatory diseases,cerebral infarction,acute myocardial infarction,and intracerebral haemorrhage;and in the respiratory diseases,pathogens unspecified pneumonias,bacterial pneumonias,and other chronic obstructive pulmona-ry diseases.Conclusion The case fatality rate of male and ≥80 years old patients in this hospital is higher.Tumor,circulatory diseases and respiratory diseases are the main causes of death.The hospital should allocate medical resources in a scientific and reasonable way according to the age,gender and disease characteristics of the patients;strengthen the prevention and treatment of tumors,circulatory diseases and respiratory diseases according to the cause of death and their distribution,improve the diagnosis and treatment level,and reduce the inpatient morbidity and fatality rate.

Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.

Objective::To examine the impact of hypertensive disorders of pregnancy (HDP) on offspring metabolomics.Methods::We searched five databases: PubMed, Ovid Embase, MEDLINE, Web of Science, and China National Knowledge Infrastructure, and included studies that reported metabolomics among human offspring born to HDP-complicated pregnancies.Results::Database search yielded 4054 articles, and after full-text screening, ten observational studies met inclusion criteria. Half of the studies had a sample size of less than 100 and were all observational studies in preeclampsia (PE) and gestational hypertension.Neonates were the most focused group in all included studies. Offspring born to HDP-complicated pregnancies exhibited statistically significant variations in blood metabolomics compared to their counterparts, characterized by amino acids, lipids, carnitine, and others (e.g., 1α,25-(OH) 2-D). Most studies reported a significant increase in differential metabolites of offspring born to HDP-complicated pregnancies. Four studies ( n = 1109) measured lipids-related metabolites, and all consistently showed that offspring born to PE-complicated pregnancies had significantly higher concentrations than non-PE exposed offspring. Conclusion::The existing evidence suggests an intergenerational effect of HDP on offspring metabolomics. Long-term follow-up studies are needed to advance the health effects of related adverse health outcomes and inform the prevention of offspring’s health.

Objective To study the application of autologous natural killer(NK)cells in the treatment of advanced renal cell carcinoma and the changes of immune function and tumor markers in patients.Methods 61 patients with advanced renal cell carcinoma admitted to Gansu Wuwei Tumour Hospital from March 2023 to April 2024 were divided into targeting group(31 cases,given supportive treatment combined with sunitinib malate capsules)and cell group(30 cases,autologous NK cells combined with targeting group)according to the patient's willingness to treat combined with propensity score matching.6 weeks was a treatment cycle,and all patients were treated for 4 cycles.The clinical efficacy of the two groups after 4 cycles of treatment and the occurrence of adverse reactions during treatment were statistically analyzed.The levels of serum cytokines,tumor markers,lymphocyte function and immune function were compared between the two groups before and after 4 cycles of treatment.Results After 4 cycles of treatment,the objective remission rate and disease control rate in the cell group were higher than those in the targeting group(P<0.05).After 4 cycles of treatment,the levels of serum hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),platelet-derived growth factor(PDGF),carcinoembryonic antigen,carbohydrate antigen 125,carbohydrate antigen 199 and alpha-fetoprotein in the two groups were lower than those before treatment,and those in the cell group were lower than those in the targeting group(P<0.012 5).After 4 cycles of treatment,the levels of serum interleukin-2,interleukin-6,tumor necrosis factor-β,interferon-γ,peripheral blood CD3+,CD4+,NK cells and CD4+/CD8+in the two groups were higher than those before treatment.The levels of serum interleukin-2,tumor necrosis factor-β,interferon-γ,peripheral blood CD3+and NK cells in the cell group were higher than those in the targeting group(P<0.012 5).The level of CD8+in peripheral blood was lower than that before treatment(P<0.012 5),but there was no significant difference between the two groups(P>0.012 5).During the treatment,there was no significant difference in the incidence of diarrhea,nausea and vomiting,alopecia,liver function damage,decreased platelet level and decreased neutrophil level between the cell group and the targeting group(P>0.05).Conclusion The treatment of advanced renal cell carcinoma with autologous NK cells could improve the level of serum cytokines,reduce the level of tumor markers,regulate the function of lymphocytes and immune function,and had a good therapeutic effect.At the same time,it would not increase the incidence of adverse reactions,and the safety was good.

Objective To analyze the characteristics of death cases in a certain tertiary hospital,providing references for hospital management decisions and the evaluation of the effectiveness of medical services.Methods The information of death ca-ses of inpatients in the hospital from 2019 to 2023 was extracted through the inpatient medical records information system,and the medical records of inpatients were retrospectively analyzed by clinical epidemiological methods.Results The cumulative number of inpatients admitted to the hospital from 2019-2023 was 459 821,with 3 250 deaths and a case-fatality rate of 0.71％.There was a decreasing trend in the case fatality rate from 0.71％in 2019 to 0.63％in 2023,but the difference was not statistically significant(APC=-3.17,P＞0.05).The case fatality rate was 0.97％for males and 0.45％for females,with males having a higher case fatality rate than females(x2=435.206,P＜0.05).The mean age of the deceased cases was(69.59±17.70)years,and the case fatality rate increased gradually with age,and the highest case fatality rate was 2.98％in the age group of ≥80 years.The difference in case fatality rate between patients of different age groups was statistically significant(x2=3 502.991,P＜0.05).The top 5 causes of death of hospitalized patients were tumor,circulatory diseases,respiratory diseases,some infec-tious and parasitic diseases and injuries,poisoning and external causes,accounting for 87.33％of the total deaths.The main causes of death in neoplasms were bronchial and pulmonary malignancies,hepatic and intrahepatic biliary malignancies,and gas-tric malignancies;in the circulatory diseases,cerebral infarction,acute myocardial infarction,and intracerebral haemorrhage;and in the respiratory diseases,pathogens unspecified pneumonias,bacterial pneumonias,and other chronic obstructive pulmona-ry diseases.Conclusion The case fatality rate of male and ≥80 years old patients in this hospital is higher.Tumor,circulatory diseases and respiratory diseases are the main causes of death.The hospital should allocate medical resources in a scientific and reasonable way according to the age,gender and disease characteristics of the patients;strengthen the prevention and treatment of tumors,circulatory diseases and respiratory diseases according to the cause of death and their distribution,improve the diagnosis and treatment level,and reduce the inpatient morbidity and fatality rate.

Objective::To examine the impact of hypertensive disorders of pregnancy (HDP) on offspring metabolomics.Methods::We searched five databases: PubMed, Ovid Embase, MEDLINE, Web of Science, and China National Knowledge Infrastructure, and included studies that reported metabolomics among human offspring born to HDP-complicated pregnancies.Results::Database search yielded 4054 articles, and after full-text screening, ten observational studies met inclusion criteria. Half of the studies had a sample size of less than 100 and were all observational studies in preeclampsia (PE) and gestational hypertension.Neonates were the most focused group in all included studies. Offspring born to HDP-complicated pregnancies exhibited statistically significant variations in blood metabolomics compared to their counterparts, characterized by amino acids, lipids, carnitine, and others (e.g., 1α,25-(OH) 2-D). Most studies reported a significant increase in differential metabolites of offspring born to HDP-complicated pregnancies. Four studies ( n = 1109) measured lipids-related metabolites, and all consistently showed that offspring born to PE-complicated pregnancies had significantly higher concentrations than non-PE exposed offspring. Conclusion::The existing evidence suggests an intergenerational effect of HDP on offspring metabolomics. Long-term follow-up studies are needed to advance the health effects of related adverse health outcomes and inform the prevention of offspring’s health.

Microfibrino-associated protein (MFAP) 2 is an extracellular matrix glycoprotein and a member of the MFAP family. It participates in the assembly of extracellular elastic microfibers.Upregulation of MFAP2 can promote the occurrence and development of various tumors and regulate multiple cancer-related signaling pathways and is related to their prognosis, making it a potential target for tumor treatment. This article summarizes the research progress on the pathogenesis, targeted therapy and prognosis of MFAP2 in malignant tumors.

A 20-year-old male patient with T-lymphoblastic lymphoma/leukemia received 9/10 human leukocyte antigen-compatible unrelated peripheral blood stem cell transplantation. He was transplanted with 5.91×10 8 mononuclear cells/kg and 2.88×10 6 CD34 + cells/kg, and neutrophil engraftment was obtained at +11 days and platelet engraftment at +9 days. After transplantation, he presented with repeatedly increased serum creatinine levels, BK virus (BKV) -associated hemorrhagic cystitis, and BKV viremia. BK virus nephropathy was diagnosed based on renal biopsy and metagenomic next-generation sequencing. After adjusting the immunosuppressant, intravenous immunoglobulin, and donor lymphocyte infusion treatment, the patient’s renal function deteriorated progressively, and he eventually died of multiple organ failure at +289 days.

Objective:To explore the clinical phenotype, genotype and genetic characteristics for a patient with unilateral paravenous retinochoroidal atrophy (PPRCA) and retinitis pigmentosa (RP) in the contralateral eye.Methods:A PPRCA pedigree which had presented at the Department of Medical Genetics of the Eye Hospital of Wenzhou Medical University in August 2021 was selected as the study subject. Clinical data of the family members were collected. The proband underwent wide-field fundus photography, wide-field autofluorescence, full-field electroretinogram (ff-ERG), visual field testing, optical coherence tomography (OCT), and fundus angiography (FFA and ICGA). Blood samples were collected from the proband and family members (parents and two sisters), and buccal mucosal cells were collected from the proband′s daughter, and genomic DNA was extracted for each family member. Whole exome sequencing (WES) was performed on the proband. Candidate variants were verified using Sanger sequencing and pathogenicity analysis. This study was approved by the Medical Ethics Committee of the Eye Hospital of Wenzhou Medical University (Ethics No.2021-212-K-185).Results:① Wide-angle fundus photography and autofluorescence showed that the right eye of the proband was consistent with PPRCA and the left eye with RP. OCT showed that the outer layer of the fovea was intact in the right eye, while disorganized outer segment was found in the fovea of the left eye, and outer segment atrophies outside the fovea were found in both eyes. The amplitudes of ff-ERG decreased significantly in both eyes, and the amplitudes in right eye were slightly higher than those of the left eye. Visual field showed a paracentral arcuate scotoma in the right eye and severe centripetal contraction in the left eye. FFA showed hyperfluorescence in the retinal vein distribution area caused by atrophy of retinal pigment epithelium of the right eye and hypofluorescence related to bone spicule pigmentation, in addition with mottled hypofluorescence of choroid in the left eye. ICGA showed mild paravenous retinochroidal atrophy of the right eye and diffuse choroid capillaries atrophy in the middle and peripheral area of the left eye. ② WES revealed that the proband had a heterozygous c. 2234C>T (p.Thr745Met) variant of the CRB1 gene. Sanger sequencing confirmed that the proband and family members except the father of the proband carried the same CRB1 gene variant. ③ Based on the "criteria and guidelines for the classification of genetic variation" and related consensus from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PM3_VeryStrong+ PM1+ PM2_Supporting + PP3). Conclusion:The heterozygous c. 2234C>T (p.Thr745Met) variant of the CRB1 gene may underlay the unilateral PPRCA with contralateral eye RP in this proband. Above findings have enriched the mutational spectrum of the CRB1 gene.