ObjectiveTo investigate the mRNA expression profile and clinical significance of the RAB24 gene in hepatocellular carcinoma （HCC） based on multi-source database including The Cancer Genome Atlas （TCGA） and clinical cohort validation. MethodsData from TCGA （n=424） were utilized to evaluate the prognostic value of RAB24 expression via Kaplan-Meier analysis and Cox regression models. An independent clinical cohort comprising 90 HCC and 30 paracancerous tissues was established to validate protein expression and histopathological features through immunohistochemistry （IHC） and routine histological staining. The TIMER database was employed to analyze the association between RAB24 and the tumor microenvironment （TME）. Furthermore， integrated with LinkedOmics， GSEA and GSVA algorithms were used to quantitatively characterize the core molecular pathways regulated by RAB24. ResultsThe mRNA expression level of RAB24 in HCC was significantly higher than that in non-tumor liver tissues （P<0.05）. Kaplan-Meier analysis revealed that the overall survival （OS） of patients in the RAB24 low-expression group was significantly longer compared to the high-expression group （HR=1.570， Log-rank P=0.01）. Cox proportional hazards regression analysis demonstrated that RAB24 expression （HR=1.480， P=0.028）， T stage （HR=2.949， P<0.001）， M stage （HR=4.077， P=0.017）， and tumor residual status （HR=2.317， P<0.001） were independent prognostic factors for HCC. RAB24 expression was highly correlated with alpha-fetoprotein （AFP） levels and immune infiltration levels （P<0.01）， and showed a significant， low-level positive correlation with the TP53 gene （Rho=0.31， P<0.01）. Quantitative analysis of the RAB24 protein in clinical samples validated that RAB24 expression in HCC tissues was significantly elevated compared to non-tumor liver tissues （P<0.05）. TIMER analysis confirmed that RAB24 expression was highly associated with the infiltration of multiple immune cells （such as B cells and NK cells）， as well as stromal and tumor purity scores in tumor tissues （P<0.01）. GSEA/GSVA enrichment revealed that the P53， MYC， and mTORC1 signaling pathways were activated in the RAB24 high-expression group； correlation analysis confirmed that the RAB24 expression level exhibited a significant， low-level positive correlation with the ribosome pathway activity score （r=0.23， P<0.01）. ConclusionsThe RAB24 gene， as a poor prognostic factor for HCC patients， is a potential biomarker for HCC diagnosis， treatment and prognosis. The study is expected to lay a theoretical foundation for the precise diagnosis and treatment of clinical HCC.

Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

ObjectiveTo screen for the patients with metabolic dysfunction-associated fatty liver disease （MAFLD） among the physical examination population， to observe the characteristics of MAFLD patients， and to compare the differences in lifestyle between the MAFLD population and the non-MAFLD population. MethodsA cross-sectional study was conducted among 6 206 individuals who underwent physical examination in a physical examination institution in Beijing from December 2015 to December 2019， and according to the new diagnostic criteria for MAFLD， the examination population was divided into MAFLD group and non-MAFLD group. Based on body mass index （BMI）， the MAFLD group was further divided into lean MAFLD group （BMI<24 kg/m²） and non-lean MAFLD group （BMI ≥24 kg/m²）. Related data were compared between groups， including demographic indicators， education level， work pressure， physical measurement indicators， and lifestyles such as sleep， diet， and exercise. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the chi-square test was used for comparison of categorical data between groups. ResultsOf all individuals in this study， 1 926 （31.1%） had MAFLD and 4 280 （68.9%） did not have MAFLD. Compared with the non-MAFLD group， the MAFLD group had significantly higher age （Z=-14.459， P<0.001）， proportion of male patients （χ²=72.004， P<0.001）， work pressure （χ²=7.744， P=0.005）， body weight （Z=-43.508， P<0.001）， BMI （Z=-47.621， P<0.001）， waist circumference （Z=-48.515， P<0.001）， hip circumference （Z=-42.121， P<0.001）， and waist-hip ratio （Z=-43.535， P<0.001）， as well as a significantly lower education level （χ²=33.583， P<0.001）. In terms of behavior， the MAFLD group had a significantly shorter sleep time （χ²=5.820， P=0.016） and a significantly faster eating speed （χ²=74.476， P<0.001）. In terms of diet， the patients in the MAFLD group consumed more high-sodium， high-sugar， and high-calorie diets （χ²=42.667， P<0.001） and low-fiber diet （χ²=4.367， P=0.008）. In terms of exercise， the MAFLD group had a significantly higher proportion of patients without exercise habits （χ²=10.278， P=0.001）. Further analysis showed that there were 202 individuals （10.5%） in the lean MAFLD group and 1 724 （89.5%） in the non-lean MAFLD group. Compared with the non-lean MAFLD group， the lean MAFLD group had significantly higher age （Z=3.368， P=0.001） and education level （χ²=9.647， P=0.002） and significantly lower proportion of male patients （χ²=27.664， P<0.001）， body weight （Z=-18.483， P<0.001）， BMI （Z=-23.286， P<0.001）， waist circumference （Z=-18.565， P<0.001）， and hip circumference （Z=-18.097， P<0.001）， and in terms of behavior， the non-lean MAFLD group had a significantly faster eating speed （χ²=4.549， P=0.033）. ConclusionThere is a relatively high prevalence rate of MAFLD among the physical examination population in Beijing， with a higher number of people with unhealthy lifestyles compared with the non-MAFLD population.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

This article reported a case of autosomal dominant intellectual developmental disorder type 22 caused by a heterozygous mutation in the ZBTB18 gene. At 24 +4 weeks of gestation, prenatal ultrasound indicated a short outer diameter of the fetal corpus callosum and bilateral ventricular dilatation. Whole-genome copy number variation analysis of the fetus showed no abnormalities. Whole exome sequencing (WES) and Sanger sequencing validation of the family revealed the fetus carried a c.1374_1383del(p.S459*) heterozygous mutation in the ZBTB18 gene (NM_205768.3), which was neither phenotypically present nor genotypically detected in the parents, suggesting a de novo mutation. Based on the clinical manifestations, the fetus was diagnosed with autosomal dominant intellectual developmental disorder type 22. After genetic counseling, the pregnant woman opted for termination of the pregnancy. This case highlights the correlation between prenatal ultrasonic detection of callosal dysgenesis and lateral ventricular enlargement and intellectual developmental disorders caused by gene mutations. Furthermore, it expands the mutation spectrum of the ZBTB18 gene, thereby facilitating prenatal diagnosis and genetic counseling.

Objective To investigate the effects of a continuous-dose administration versus different dosage regimens of polyethylene glycol electrolyte solution(PEG)taken in two doses with a 12-hour interval on bowel cleansing efficacy,with the goal of optimizing bowel preparation protocols and improving patient tolerability.Methods 232 patients who underwent painless colonoscopy and used PEG as a bowel cleanser from June 2024 to September 2024 were selected as study subjects.Participants were divided into three groups:the control group(3.00 L PEG continuous dose),experimental group A(0.75 L+2.25 L PEG),and experimental group B(1.50 L+1.50 L PEG).All patients underwent painless colonoscopy within 4～6 h after completing PEG intake.The interval between the two doses of PEG in group A and group B was 12 h.The bowel cleansing efficacy was assessed by using the Boston bowel preparation scale(BBPS),and the rates of colon polyp detection,adverse reactions,sleep duration,and tolerability were recorded.Results There were no significant statistical differences in BBPS scores and colon polyp detection rates among the three groups(P>0.05).Experimental group B experienced the least adverse reactions,followed by experimental group A,while the control group reported the most significant adverse reactions(P<0.05).The timing of PEG administration did not have a significant impact on sleep duration among the three groups(P>0.05).Patients in experimental group B showed good tolerability to PEG and were willing to accept this bowel preparation regimen,followed by group A,while the control group exhibited the poorest tolerability,with significant statistical differences among the three groups(P<0.05).Conclusion The continuous administration and divided administration of PEG have no significant impact on the effectiveness of intestinal cleansing and the detection rate of colonic polyps.However,the divided PEG regimen with a 12 h interval results in fewer adverse reactions and better tolerance,especially the optimal regimen of taking 1.50 L PEG in two doses with a 12 h interval.

Objective:To discuss the expression and clinical significance of inositol polyphosphate-4-phosphatase type Ⅱ(INPP4B)gene in hepatocellular carcinoma(HCC)based on The Cancer Genome Atlas(TCGA)database and experimental verification with clinical samples.Methods:Based on data from 424 clinical samples in the TCGA database(including 374 HCC tissues and 50 paracarcinoma tissues),Kaplan-Meier method and Cox regression analysis were used to evaluate the relationship between INPP4B gene and the clinical characteristics and survival prognosis of the HCC patients.The correlations between INPP4B gene and the number of 24 types of immune cells,matrix,immune cell infiltration and tumor purity in tumor tissue,and the expression level of the high-frequency mutant gene tumor protein 53(TP53)in HCC were analyzed.The clinicopathological data and paraffin-embedded tissue sections of 60 HCC patients treated with surgical resection from December 2022 to December 2023 were collected.According to clinical diagnosis,they were divided into poorly differentiated group(HCC-L group),moderately differentiated group(HCC-M group)and well-differentiated group(HCC-H group),with 20 cases in each group;20 patients during the same period who underwent biopsy and were pathologically diagnosed as non-tumor were selected as normal group,and their clinicopathologic data and liver tissue paraffin sections were collected.HE staining was used to observe the pathomorphology of HCC tissue and normal liver tissue of the subjects in various groups;immunohistochemistry method was used to detect the expressions of Ki-67 and INPP4B proteins in the HCC tissue and normal liver tissue of the subjects in various groups.Results:The TCGA database analysis results showed that compared with normal tissue,the expression level of INPP4B mRNA in HCC tissue was significantly increased(P<0.01).Compared with INPP4B low expression group,the overall survival(OS)of the patients in INPP4B high expression group was significantly prolonged(P<0.05).The univariate Cox regression analysis results showed that tumor stage,pathological stage,tumor status and residual tumor had impacts on OS of the HCC patients(P<0.05).The univariate regression analysis results showed that the INPP4B prognostic risk model score ratio was HR=0.781,95％confidence interval(CI):0.552-1.105,P=0.168.The AUC value for the impact of INPP4B on OS of the HCC patients was 0.558,indicating that the INPP4B gene prognostic risk model had certain predictive value in survival prognosis.The INPP4B mRNA expression level was not correlated with TNM stage,stage,patient gender,age,race or body mass index(BMI)(P>0.05).In tumor tissue with high and low INPP4B expression,22 types of immune cells showed statistically significant differences(P<0.05);the INPP4B mRNA expression level was positively correlated with the number of 23 types of immune cells except T helper(Th)17 cells(r>0),among which all Th cells except natural killer(NK)CD56+cells were statistically significant(P<0.01);INPP4B was significantly correlated with matrix(r=0.475),immune cell infiltration(r=0.641)and tumor purity(r=0.599)in tumor tissue(P<0.01).INPP4B was correlated with TP53(r=0.287,P<0.01).The HE staining results showed that clear and complete lobular structure,neatly arranged cells and slight inflammatory cell infiltration were observed in liver tissue of the subjects in normal group;completely destroyed lobular structure,significant hepatocellular steatosis,massive inflammatory cell infiltration,and lesions such as ballooning degeneration and small cell hyperplasia in some cells were observed in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups,and the lower the HCC differentiation degree,the more severe the tissue destruction;The immunohistochemistry results showed that compared with normal group,the expression levels of Ki-67 protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly increased(P<0.01),and the lower the differentiation degree of the HCC patients,the higher the Ki-67 positive rate.Brownish-yellow granules evenly distributed in the cells and INPP4B protein was highly expressed in liver tissue of the subjects in normal group;compared with normal group,the expression levels of INPP4B protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly decreased(P<0.01),and the lower the differentiation degree of the HCC tissue,the lower the INPP4B positive rate.Conclusion:INPP4B is a protective factor for the prognosis of HCC patients;as a new tumor suppressor gene,INPP4B may become a potential target for new drug screening in HCC treatment.

Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5％(2 576/4 479)]was higher than that of female patients[42.5％(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0％(2 241/4 479)].About 90.0％of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6％of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5％of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8％.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6％).98.6％of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.

Objective To investigate the effect of miR-132-3p on epithelial-mesenchymal transition(EMT)of trophoblast cells through targeted regulation of the SIRT1/NF-κB pathway.Methods Placental tissues from 37 pre-eclampsia(PE)patients who underwent cesarean section in Zhengzhou Women&Infants Hospital and 37 normal pregnant women who underwent cesarean section were collected as the research group and control group,respectively.RT-qPCR was performed to detect the expression of miR-132-3p and SIRT1 in tissues.During the logarithmic pro-liferation phase,HTR-8/SVneo cells were grouped into inhibitor negative group,miR-132-3p inhibitor group,mimic negative group,miR-132-3p overexpression group,miR-132-3p inhibitor+interference negative group,and miR-132-3p inhibitor+interference SIRT1 group,with untransfected HTR-8/SVneo cells as the blank group.CCK-8,Transwell assay,scratch assay,and RT-qPCR were used to detect the proliferation,invasion,migration,and changes in miR-132-3p and SIRT1 mRNA expression of HTR-8/SVneo cells.Western blot was used to detect the expression levels of EMT related proteins and SIRT1,NF-κB proteins.Dual luciferase was used to validate the targeting relationship between miR-132-3p and SIRT1.Results The level of miR-132-3p in the research group was significantly higher than that in the control group,while the SIRT1 mRNA was lower(P＜0.05).The level of miR-132-3p,E-cadherin,p-NF-κBp65/NF-κBp65 in the miR-132-3p inhibitor group was lower than those in the inhib-itor negative group and blank group.The proliferation rate,invasion cell number,migration rate,level of vimentin,N-cadherin,and SIRT1 were all higher(P＜0.05).The miR-132-3p,E-cadherin,p-NF-κBp65/NF-κBp65 in the miR-132-3p overexpression group were higher than those in the mimic negative group,the proliferation rate,inva-sion number,migration rate,vimentin,N-cadherin,and SIRT1 were lower(P＜0.05).The level of E-cadherin and p-NF-κBp65/NF-κBp65 in the miR-132-3p inhibitor+interference SIRT1 group was higher than those in the miR-132-3p inhibitor+interference negative group(P＜0.05),the proliferation rate,invasion number,migration rate,vimentin,N-cadherin,and SIRT1 expression were lower(P＜0.05).MiR-132-3p targeted regulation of SIRT1 expression(P＜0.05).Conclusions Inhibition of miR-132-3p promotes the EMT,proliferation,invasion,and migration of trophoblast cells by targeting and activating the SIRT1/NF-κB pathway.

Background: The genus Atractylodes, native to East Asia, encompasses several species that serve as sources for the widely used traditional Chinese medicines Atractylodis Macrocephalae Rhizoma and Atractylodis Rhizoma. However, the international trade arouses concern regarding potential confusion and misidentification of Atractylodes species. Objective: A comprehensive understanding of the chemical diversity is crucial for ensuring the quality and exploring the potential variations in medicinal efficacy of Atractylodes. Methods: The GC-MS/MS-based metabolomics and multivariate statistical analysis identified 589 differentially accumulated metabolites across 5 Atractylodes species. Results: A total of 150 metabolites were predicted as potential chemical markers for species differentiation and quality assessment of Atractylodes. According to the metabolic profiles, the species of Atractylodes can be roughly classified into three categories: A. lancea and A. coreana with the volatile oil components being mainly atractylodin and β-eudesmol; A. macrocephala with the biomarker being atractylon; and A. japonica and A. carlinoides lying between the two categories above. Conclusions: Metabolomic results indicated that the metabolic profiles of A. carlinoides and A. macrocephala were similar and distinct from those of the other three species. Sesquiterpenoids were the main chemical components in the rhizome of A. carlinoides, which indicated the potential medicinal value of this plant.