OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps

Objective: To construct prediction models of female stress urinary incontinence (SUI), and evaluate the efficacy of each model, so as to provide reference for the early diagnosis of SUI. Methods: Female SUI patients treated in our hospital during Oct. 2019 and Oct. 2023 and healthy women undergoing physical examination during the same period were involved. Women 42 days after delivery were included in the postpartum group (n=611), and perimenopausal and postmenopausal women were included in the non-postpartum group (n=409). The number of random seeds was set and the participants were divided into the training and verification sets in a ratio of 7∶3. Relevant clinical data were collected, and meaningful variables were screened using single factor and Lasso regression, which were then incorporated into the K-nearest neighbor method (KNN), support vector machine (SVM)，decision tree (DT) and random forest (RF) algorithms. The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve (AUC) of the models were calculated to screen out the optimal model. Results: There were 352 SUI patients (57.6%) in the postpartum group. According to single factor and Lasso regression, significant variables included age, body mass index (BMI), maximum rapid muscle stage, parity, bladder neck mobility (BND), urethral rotation angle (URA), lateral perineal incision, past incontinence, and constipation. In the verification set, the AUC of KNN，SVM，DT and RF models were 0.881，0.878，0.750 and 0.905,respectively; the AUC, accuracy, F1 index and Kappa value of RF model were the largest. In the non-postpartum group, there were 260 SUI patients, accounting for 63.6%. The significant variables were age，BMI, maximum value and recovery time of fast muscle stage, mean value of slow muscle stage, post-resting stage variability, vaginal delivery, past incontinence, and constipation. In the verification set, the AUC of KNN,SVM，DT and RF models were 0.819,0.805，0.603 and 0.830, respectively; the AUC, accuracy, Kappa value of the RF model were the largest. Conclusion: This study successfully established 4 prediction models for the incidence of SUI in women at 42 days postpartum, perimenopausal and postmenopausal women based on machine learning. Among them, the model adopting the RF algorithm had the best prediction efficiency.

Hospital culture is the sum of common values， codes of conduct， and working methods formed by internal employees within the hospital， and it is the spiritual pillar and core of cohesion of the hospital. Party-building leadership plays an important role in promoting hospital culture construction， including strengthening values guidance， enhancing team cohesion， facilitating management system innovation， and shaping social image and brand value. By analyzing the effectiveness of a series of Party-building activities carried out by Xi’an No. 9 Hospital in recent years， this paper explored the effect and significance of Party-building leadership in promoting hospital culture construction in the new era， as well as proposed guiding strategies for strengthening Party-building work in promoting hospital culture construction in the new era， so as to promote high-quality development of the hospital.

ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop （TTFL） of biorhythm in the rat model of non-alcoholic fatty liver disease （NAFLD） and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank （n=20）， model （n=15）， and low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） modified Ditan tang （n=10） groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage， and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid （NEFA） assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining， and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 （BMAL1/ARNTL） in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1， circadian locomotor output cycles kaput （CLOCK）， period circadian clock 2 （PER2）， and cryptochrome1 （Cry1） in the hypothalamus and liver were determined by Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed elevated levels of TG， TC， LDL-C， AST， and ALT （P<0.01） and a lowered level of HDL-C （P<0.05） in the serum， elevated levels of TG and NEFA in the liver （P<0.01）， pyknosis and deep staining of hypothalamic neuron cells， and a large number of vacuoles in the brain area. In addition， the model group showed lipid deposition in the liver， up-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.01）， and down-regulated mRNA and protein levels of Cry1 and PER2 （P<0.01） in the hypothalamus and liver. Compared with the model group， all the three modified Ditan tang groups showed lowered levels of TG， TC， LDL-C， ALT， and AST （P<0.05， P<0.01） and an elevated level of HDL-C （P<0.05） in the serum， and lowered levels of TG and NEFA （P<0.05， P<0.01） in the liver. Furthermore， the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells， reduced lipid deposition in the liver， down-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.05， P<0.01）， and up-regulated mRNA and protein levels of Cry1 and PER2 （P<0.05， P<0.01） in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK， BMAL1， Cry1， and PER2 in the TTFL of NAFLD rats.

Objective To investigate the change in choroid plexus(CP)volume in Parkinson's disease(PD)patients with different cognitive states and its correlation with structural volumes of other brain regions.Methods A cross-sectional study was conducted on 48 PD patients admitted in Department of Neurosurgery of the First Affiliated Hospital of Army Medical University between May 2023 and April 2024,and on 35 healthy controls(HC)recruited through a physical exam center.According to the results of Mini-Mental State Examination(MMSE),the patients were divided into PD with cognitive impairment(PD-CI)group(n=27)and PD with normal cognitive function(PD-NC)group(n=21).3.0T magnetic resonance imaging(MRI)was performed using MPRAGE sequences,and CP volume and volumes of other brain regions were obtained using FreeSurfer 6.0 software.The CP volume was adjusted by calculating the ratio of its volume to estimated total intracranial volume(eTIV).After controlling for confounders,partial correlation analysis was used to assess the relationship between the CPV/eTIV ratio and the volumes of other brain regions as well as cognitive scale scores.Additionally,multiple linear regression analysis was performed to further explore the relationship between CPV and cognitive function in the PD-CI group.Results Compared to the HC group,the CPV in the PD-CI group was significantly larger(P=0.029).In the PD-CI group,the CPV/eTIV ratio showed significant positive correlations with the volume of the lateral ventricles(r=0.689,P=0.001),the volume of the third ventricle(r=0.592,P=0.006),the volume of cerebrospinal fluid(CSF)(r=0.508,P=0.022),and white matter hyperintensities(WMH)(r=0.486,P=0.030),but was negatively correlated with the volume of the caudate nucleus(r=-0.530,P=0.016),the volume of the thalamus(r=-0.477,P=0.033),and the MMSE scores(r=-0.483,P=0.031).But in the PD-NC group,the CPV/eTIV ratio was only positively correlated with CSF volume(r=0.571,P=0.021).Multiple linear regression analysis indicated that the CPV/eTIV ratio and MMSE scores remained significantly negatively correlated in the PD-CI group(β=-0.388,P=0.046).Conclusion Cognitive impairment in PD patients may be closely associated with the change in CP volume,suggesting that the volume can serve as a potential imaging marker in assessment of cognitive impairment in PD patients.

The aim of this study is to explore the immunogenicity of African swine fever virus p37 recombinant protein in mice.C57BL/6J mice were immunized subcutaneously in the abdomen using p37 recombinant protein as antigen.The second immunization was performed 21 d after the first immunization.Serum-specific antibody levels were detected by ELISA;serum cytokine levels were detected using a multifactor assay technique;mice splenic lymphocytes were isolated 7 d after sec-ondary immunization,and the number of splenic lymphocytes secreting IFN-γ after recombinant protein stimulation was detected by ELISpot;and the ratio of CD4+T cells to CD8+T cells was detected by flow cytometry.The results of indirect ELISA showed that p37 recombinant protein could stimulate mice to produce high levels of specific antibodies;ELISpot showed that p37 recom-binant protein could significantly stimulate splenic lymphocytes to produce IFN-γ(P＜0.001)and activate cellular immune responses;the results of flow cytometry showed that it could signifi-cantly stimulate the differentiation of T-lymphocytes to CD4+T-lymphocytes(P＜0.001).In ad-dition,serum levels of IL-2,IL-4,IFN-γ,and TNF-α immune-related cytokines were significantly higher after the second immunization.Immunization of mice with p37 recombinant protein induced strong humoral and cellular immune responses with good immunogenicity,providing reference for the subsequent epitope identification and functional study of p37 protein and the antigen screening of ASF mRNA vaccine.

Objective To evaluate the efficacy and safety of tislelizumab intravenous injection combined with pirarubicin intravesical instillation in the treatment of non-muscle-invasive bladder cancer(NMIBC).Methods This study is a randomized controlled trial,including 80 patients with NMIBC who underwent transurethral resection of bladder tumor(TURBT)at the urology department of Central Hospital of Guangdong Nongken from January 1,2021,to December 31,2022.The patients were randomly assigned to either the experi-mental group(treated with tislelizumab intravenous injection combined with pirarubicin intravesical instillation,n=40)or the control group(treated with pirarubicin intravesical instillation alone,n=40).The primary efficacy endpoints included progression-free survival(PFS),recurrence rate,and radiological progression rate.Safety was assessed by the type and incidence of treatment-related adverse e-vents(AEs).Results The median PFS in the experimental group was significantly longer than that in the control group(16 months vs 9months,P=0.034).The 1-year and 2-year recurrence rates in the experimental group were significantly lower than in the control group(7.5％vs 15.0％,P=0.034;12.5％ vs 22.5％,P=0.019).The radiological progression rate in the experimental group was significantly lower than that in the control group(7.5％vs20.0％,P=0.019).No treatment-related deaths occurred in either group.The incidence of fatigue was significantly higher in the experimental group than in the control group(25.0％vs 10.0％,P=0.048),while other adverse events showed no significant differences and were predominantly mild to moderate(Grade 1-2),manageable with symptomatic treatment.Conclusion Tislelizumab intravenous injection combined with pirarubicin intravesical instillation significantly prolongs PFS,reduces recurrence rates,and inhibits tumor progression in NMIBC patients,with good safety and tolerability.This combi-nation offers a safe and effective new strategy for postoperative NMIBC management.

Purpose To explore the application value of cardiac magnetic resonance(CMR)mapping and strain techniques in assessing ventricular function changes in patients with severe alcohol use disorder(AUD).Materials and Methods A retrospective analysis was conducted on 32 male patients with severe AUD as the study group in Hefei Fourth People's Hospital from January 2023 to April 2024,compared with 30 age-and gender-matched healthy subjects as the control group.Clinical data and CMR results were collected for all participants.CMR parameters included conventional functional parameters such as left and right ventricular ejection fraction,volume index and mass index;tissue characterization parameters such as Native T1,T2 mapping and extracellular volume fraction(ECV);and strain parameters including global longitudinal strain(GLS),global circumferential strain(GCS)and global radial strain(GRS)for both ventricles.The differences in the above indexes between the two groups were compared.Results The left ventricular end-diastolic volume index in the AUD group was significantly higher than in the control group(t=3.799,P<0.001).The left ventricular strain values(GLS,GCS,GRS)in the AUD group were significantly lower than those in the control group(t=4.459,4.435,-4.759,all P<0.001).The Native T1,T2 and ECV in the AUD group were significantly higher than those in the control group(t=6.301,5.650,7.069,all P<0.001).For the right ventricle,only right ventricular GLS and right ventricular GCS were significantly lower than in the control group(t=8.703,-2.814,both P<0.01).Conclusion CMR feature tracking technology can early identify ventricular function abnormalities in AUD patients.The increase in Native T1,T2 mapping and ECV suggests the presence of myocardial edema and fibrosis in AUD patients,which is closely related to left ventricular dysfunction.Multi-parameter CMR evaluation provides important diagnostic evidence for the early detection of cardiac involvement in severe AUD patients.

Objective:To optimize the previously established Improved Membrane Filtration(ISET)method for de-tecting circulating tumor cells(CTCs)and to develop and validate a new,reliable CTC detection method by combining it with immunofluorescence techniques.Methods:The study involved optimizing the CTC detection system using mixed samples of gastric cancer 803 cell lines and peripheral blood(PB)from healthy volunteers to simulate the peripheral blood of cancer patients.The optimized system was validated using peripheral blood samples from 23 patients with ad-vanced(Ⅲ/Ⅳ)cancer,employing the ISET technique combined with immunocytochemistry(ICC)and paraffin block im-munohistochemistry(IHC)identification techniques.A cohort of 74 patients with various cancer types was used to com-pare the diagnostic performance of the membrane filtration combined with immunofluorescence(ISET-ICC)system against the CTC-Biopsy and CellSearchTM methods.Results:By adding a red blood cell lysis step and increasing the membrane pore size to 10 μm,the filtration time of the ISET method was reduced by threefold.The ISET-ICC detection method achieved a CTC positivity rate of 65.2％.The combination of the ISET-ICC system with the cell paraffin block-IHC method enhanced the reliability of identifying circulating tumor cells undergoing epithelial-mesenchymal transition(EMT-CTCs).The ISET-ICC technique demonstrated a significantly higher CTC positivity rate(17.6％;13/74)within the study cohort compared to the CellSearchTM method,which showed a CTC positivity rate of 12.2％(9/74;x2=10.21,P=0.007).The difference in positive detection rates among patients at different stages was statistically significant(x2=3.64,P=0.029),with a notably higher CTC detection rate in stage Ⅳ patients compared to those in stages Ⅰ-Ⅲ(x2=6.76,P=0.001).Conclusion:The improved ISET-ICC system effectively detects CTCs across various cancer types and dem-onstrates greater accuracy compared to the CellSearchTM system.

Objective:To investigate genetic findings and pregnancy outcomes in fetuses with omphalocele.Methods:This retrospective study analyzed data from 502 fetuses with prenatally diagnosed omphalocele who underwent genetic testing at Guangzhou Women and Children's Medical Center and Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2014 and March 2024. Testing methods included karyotyping, chromosomal microarray analysis (CMA), methylation-specific multiplex ligation-dependent probe amplification, and whole-exome sequencing (WES). Cases were categorized as non-isolated ( n=340) or isolated ( n=162) based on ultrasound findings. Differences in genetic abnormality detection rates and pregnancy outcomes were analyzed using Mann-Whitney U test, independent samples t-test, and Chi-square test (or Fisher's exact test). Results:Among 502 fetuses, karyotyping plus CMA detected chromosomal abnormalities in 223 cases (44.4%, 223/502), including trisomy 18 (57.0%, 127/223) and trisomy 13 (23.3%, 52/223). CMA additionally identified nine pathogenic copy number variations (1.8%, 9/502) and five uniparental disomies (1.0%, 5/502), increasing the total diagnostic yield from 44.4% to 47.2%. The genetic abnormality rate was significantly lower in isolated (14.8%, 24/162) versus non-isolated omphalocele (64.7%, 220/340) ( χ2=109.34, P<0.001). WES detected variants in nine of 16 karyotype/CMA-negative cases, including five pathogenic variants involving PIK3CA and CDKN1C. Eight imprinting disorders (1.6%, 8/502) were identified, including five Beckwith-Wiedemann syndrome cases. Among 499 cases with follow-up, 401 (80.4%, 401/499) underwent pregnancy termination. Live birth rate was higher in isolated versus non-isolated groups [42.5% (69/162) vs. 8.5% (29/340), χ2=77.67, P<0.001]. Three cases were lost to follow-up. The one-year survival rate was 93.9% (92/98) in live-born infants. Conclusion:Aneuploidy (particularly trisomy 18) is the primary genetic etiology of omphalocele. CMA and WES significantly improve diagnostic yield. Isolated omphalocele has a more favorable prognosis, while non-isolated cases show significantly higher genetic abnormality rates. A stratified testing strategy is recommended: karyotyping plus CMA for isolated cases and prioritization of WES for multiple anomalies.