OBJECTIVES: To explore the association of the expression of WW domain-containing ubiquitin E3 ligase 1 (WWP1) with immune infiltration in tumor microenvironment (TME) of ovarian cancer. METHODS: Ovarian cancer patient data from The Cancer Genome Atlas (TCGA) were used to analyze the association of WWP1 expression with patient prognosis. TISCH2 was utilized to analyze the changes in immune cell subtypes in TME of metastatic tumor and after chemotherapy. The impact of WWP1 on immune cell infiltration, somatic copy number alterations of WWP1 and evolution of immune cell subtypes was evaluated using TIMER and TIGER pseudo-time analysis. A deep learning model was used to analyze TCGA pathological images to investigate the effect of WWP1 on TME of ovarian cancer. RNA-seq analysis was conducted to identify the differentially expressed genes in WWP1-overexpressing SKOV3 cells and validate immune infiltration. Multicolor immunofluorescence assay was used to analyze the immune markers in SKOV3 and SKOV3/DDP cell xenografts in nude mice. RESULTS: The patients with high WWP1 expression levels had significantly lower overall survival rate (P=0.0012). High WWP1 expression levels and Stage IV disease were both associated with a poor prognosis (P<0.05). In metastatic ovarian cancer or after chemotherapy, the percentages of malignant tumor cells and tumor-associated fibroblasts increased in the TME, accompanied by elevated WWP1 levels. WWP1 expression level was positively correlated with pro-tumorigenic immunosuppressive cells (r=0.1323-0.3955, P<0.05) and negatively with tumor-inhibiting immune cells (r=-0.1949- -0.1333, P<0.05). Specific copy number alterations of WWP1 also influenced CD8⁺ T cell percentage and neutrophil infiltration levels in the TME. RNA-seq analysis of WWP1-overexpressing SKOV3 cells and immunofluorescence assay of the tumor-bearing mice yielded findings consistent with those of bioinformatics analysis. CONCLUSIONS WWP1 may serve as a prognostic biomarker and a potential target for immune regulation in the TME of ovarian cancer.
Female ; Ovarian Neoplasms/genetics* ; Humans ; Ubiquitin-Protein Ligases/metabolism* ; Tumor Microenvironment/immunology* ; Animals ; Mice ; Cell Line, Tumor ; Mice, Nude ; Prognosis ; Gene Expression Regulation, Neoplastic

The red doctor spirit is the advanced culture of the Communist Party of China formed under a specific historical and cultural background. It can be summarized as “political firmness， excellent technology， working hard， and healing the wounded and rescuing the dying.” This content has many hidden similarities and integrations with the goal of cultivating humanistic literacy for medical students in military medical universities. This paper aimed to identify the important connection points between the red doctor spirit and the contents and goals of medical humanities teaching， as well as integrate the red doctor spirit into medical humanities teaching by various dimensions， including systematic reconstruction of textbook content， immersive innovation in teaching form， three-dimensional support in resource construction， and innovative implementation of narrative medicine teaching. It also further explored the extension of the red doctor spirit in military medical humanistic literacy， namely， revolutionary humanism and revolutionary heroism， thereby enhancing the effectiveness of medical humanistic teaching.

ObjectiveTo investigate the effect of the multidisciplinary team （MDT） management model in improving the prognosis of patients with cirrhotic portal hypertension. MethodsA total of 86 patients with cirrhotic portal hypertension who were admitted to Shenzhen Third People’s Hospital from May 2022 to July 2024 were enrolled， and according to whether the MDT treatment regimen was implemented， they were divided into execution group with 51 patients and non-execution group with 35 patients. Baseline clinical data were collected， and the patients were observed in terms of gastrointestinal bleeding， hepatic encephalopathy， liver cancer， and death from admission to the end of follow-up （January 2025）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves for the cumulative incidence rates of endpoint events （gastrointestinal bleeding， hepatic encephalopathy， liver cancer， and death）， and the Log-rank test was used for comparison between groups. The Cox proportional-hazards regression model analysis was used to investigate the effect of MDT management on the prognosis of patients. ResultsThere were significant differences between the execution group and the non-execution group in diameter of the portal vein （t=1.216， P=0.017） and ascites （χ²=4.515， P=0.034） at baseline. The patients were followed up for 14.6±6.2 months， and the survival curve analysis showed that there was a significant difference in the cumulative incidence rate of gastrointestinal bleeding between the two groups （χ²=4.573， P=0.024）， while there were no significant differences in the incidence rates of other outcome events between the two groups （all P>0.05）. The Cox regression analysis showed that the execution group had a reduced risk of gastrointestinal bleeding （hazard ratio=0.262， 95% confidence interval： 0.110 — 0.630， P=0.003）. ConclusionImplementation of the MDT treatment regimen can significantly reduce the short-term risk of gastrointestinal bleeding in patients with cirrhotic portal hypertension， while its long-term benefits require further follow-up verification.

Objective To investigate the changes and clinical significance of serum kynurenine(KYN)and quinolinic acid(QA)levels in elderly patients with chronic kidney disease(CKD)complicated with major ad-verse cardiovascular events(MACE).Methods A total of 156 elderly patients with CKD treated in the Fourth People's Hospital of Taizhou from February 2022 to February 2024 were selected as the CKD group,and were divided into the MACE group(n=45)and the non-MACE group(n=111)according to whether they were complicated with MACE.A total of 80 healthy people who underwent physical examination in the Fourth People's Hospital of Taizhou during the same period were selected as the control group.High perform-ance liquid chromatography-tandem mass spectrometry was used to measure the serum KYN and QA levels in each group.Multivariate Logistic regression was used to analyze the risk factors for MACE in elderly CKD pa-tients.The receiver operating characteristic curve was used to analyze the predictive value of serum KYN and QA for MACE in elderly CKD patients.Results The levels of KYN and QA in CKD group were higher than those in control group(P<0.05).The age,levels of C-reactive protein,24 h urinary protein,KYN and QA in MACE group were higher than those in non-MACE group(P<0.05).The increased levels of 24 h urinary protein,C-reactive protein,KYN and QA were risk factors for MACE in elderly CKD patients(P<0.05).The area under the curve(AUC)of combined detection of serum KYN and QA for predicting MACE in elderly CKD patients was 0.920(95%CI 0.891-0.959),which was greater than the AUC of KYN[0.836(95%CI 0.804-0.879)]and QA[0.843(95%CI 0.798-0.887)]alone,and the difference was statistically significant(Z=4.023,3.897,P<0.05).Conclusion The levels of serum KYN and QA are increased in elderly CKD pa-tients with MACE,which are related to renal function.The combination of serum KYN and QA can effectively predict the risk of MACE in elderly CKD patients.

Objective This study aims to explore the effects of Minimally Invasive Extracorporeal Circulation(MECC)on systemic inflammatory response and transfusion requirements following Coronary Artery Bypass Grafting(CABG).Methods A total of 126 patients who underwent CABG from January 2023 to January 2024 were selected and randomly divided into an observation group and a control group,with 63 patients in each group.The observation group received MECC,while the control group was treated with Conventional Extracorporeal Circulation(CECC).Inflammatory response indicators,immune system function,coagulation function,renal function,cardiac function,and clinical symptoms were monitored preoperatively and at 24,48,and 72 hours postoperatively for comparison and analysis.Results At 24 hours postoperatively,CRP,IL-6 and TNF-α levels in the observation group were(18.5±3.7)mg/L,(15.2±3.4)pg/mL and(25.3±5.6)pg/mL,respectively,which were significantly lower than those in the control group(P＜0.05).At 48 hours postoperatively,the CD4+/CD8+ratio in the observation group was 1.6±0.3,which was higher than that in the control group(P＜0.05).At 72 hours postoperatively,the PT and APTT in the observation group were(12.1±1.2)seconds and(30.4±3.2)seconds,respectively,which were significantly lower than those in the control group(P＜0.05).Additionally,72 hours after surgery,SCr and BUN in the observation group were(1.1±0.2)mg/dL and 14.6±3.1 mg/dL,respectively,which were significantly lower than those in the control group(P＜0.05).In terms of cardiac function indexes,at 24 hours postoperatively,CI,LVEF,cTnⅠ and BNP in the observation group were(2.6±0.5)L/min/m2,(55.6±4.0)％,(0.14±0.03)ng/mL,and(280±30)pg/mL,respectively,which were significantly better than those in the control group(P＜0.05).At all postoperative time points,the VAS score,complication rate,length of hospital stay and ICU stay were significantly better in the observation group than in the control group(P＜0.05),with the VAS score at 24 hours postoperatively being(4.8±1.2)compared to(5.5±1.3)in the control group(P＜0.05).Conclusions MECC demonstrates significant advantages in attenuating systemic inflammatory response after CABG,protecting multi-system function,reducing postoperative blood transfusion requirements,and improving postoperative recovery.Compared with traditional extracorporeal circulation,MECC effectively reduce postoperative inflammatory reactions and complications,enhancing the quality of life for patients post-surgery,and shows broad clinical application prospects.

OBJECTIVE: To explore the genetic testing outcomes of a fetal family with Thyroid dyshormonogenesis type 5 (TDH5) and familial Neurofibromatosis type 1 (NF1), and to clarify the association between clinical manifestations and genetic variations. METHODS: One case of a TDH5 combined with familiar NF1 fetus treated at Gansu Maternal and Child Health Hospital in January 2024 was selected as the research subject. The clinical and family history data of the fetus were collected by retrospective research method. 10-15 mL of fetal amniotic fluid, and 2-3 mL of peripheral blood from the parents, sister, and grandfather of the fetus were collected, and genomic DNA was extracted for trio whole-exome sequencing (trio-WES). The Sanger sequencing was utilized to validate candidate variants for family verification. According to the Standards and Guidelines for the Interpretation and Reporting of Sequence Variants of the American Society of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG guidelines), the pathogenicity of the detected variants was classified. This study has been approved by the Medical Ethics Committee of Gansu Maternal and Child Health Hospital [Ethics No.（2021）GSFY（65）]. RESULTS: The fetal ultrasound indicated the nuchal translucency (NT) thickening, and the thyroid function test results of the sister showed an increase in thyroid stimulating hormone and a decrease in free thyroid hormone. Simultaneously, there were cafe-au-lait macules of various sizes in multiple parts of the body of the sister, and the mother had a similar cafe-au-lait macules phenotype. The trio-WES results revealed that there was a c.413dupA (p.Tyr138*) frameshift mutation in exon4 and c.573G>A (p.Trp191*) nonsense mutation in exon5 of the fetal DUOXA2, which were inherited from the mother and father, respectively. In accordance with the ACMG guidelines, they were classified as pathogenic variant (PVS1+PM2_Supporting+PM3) and likely pathogenic variant (PVS1+PM2_Supporting), respectively. And the nonsense mutation c.6972C>A (p.Tyr2264*) was detected in exon46 of the NF1 in the fetus, inherited from the mother maternal grandfather. The genetic testing results of the first sister and proband in this case were consistent, and the DUOXA2 and NF1 of the second sister were both wild-type. According to the ACMG guidelines, c.6972C>A (p.Tyr2264 *) was classified as pathogenic variant (PVS1+PS4_Supporting+PP4+PM2_Supporting). CONCLUSION The mutations in the DUOXA2 gene c.413dupA (p.Tyr138*) and c.573G>A (p.Trp191*), and the NF1 gene c.6972C>A (p.Tyr2264*) might be the genetic causes of TDH5 combined with familiar NF1 in proband. The discovery of the DUOXA2 gene c.573G>A (p.Trp191*) enriches the spectrum of pathogenic gene variations.
Humans ; Female ; Pedigree ; Pregnancy ; Neurofibromatosis 1/complications* ; Male ; Genetic Testing ; Adult ; Thyroid Dysgenesis/genetics* ; Fetus ; Exome Sequencing ; Mutation

Background The incidence of mental disorders is steadily increasing.However,antipsychotic medications,commonly used in treatment,can lead to drug-induced amenorrhea in female patients.This side effect significantly reduces medication adherence and increases the risk of disease recurrence.Therefore,addressing drug-induced amenorrhea in female patients has become an urgent problem requiring effective solutions.Objective To explore the efficacy and safety of traditional Chinese medicine compound in treating antipsychotic-induced amenorrhea,so as to provide guidance for the treatment of this condition using traditional Chinese medicine compound.Methods On September 4,2022,a computerized search was conducted on across multiple databases,including China National Knowledge Infrastructure,VIP Database,Wanfang Database,China Biomedical Literature Database,PubMed,Cochrane Library and Embase,and randomized controlled trials(RCT)of traditional Chinese medicine compound in treating antipsychotic-induced amenorrhea were collected.The quality of the included literature was assessed using Cochrane 5.3 bias risk assessment tool.Meta-analysis was performed to assess the total effective rate,cure rate,incidence of adverse reactions and recurrence rate using RevMan 5.3.Results Ultimately,22 RCT involving 1879 patients were included.Meta-analysis results showed that the total effective rate(RR=1.29,95%CI:1.16～1.44)and cure rate(RR=1.62,95%CI:1.45～1.80)of traditional Chinese medicine compound or its combination with western medicine in treating antipsychotic-induced amenorrhea were significantly higher compared to western medicine alone.Moreover,the incidence of adverse reactions(RR=0.56,95%CI:0.41～0.76)and recurrence rate(RR=0.16,95%CI:0.06～0.42)were significantly lower than those of western medicine alone.Conclusion Traditional Chinese medicine compound may offer benefits in ameliorating antipsychotic-induced amenorrhea and its safety is better than simple western medicine treatment.

Objective To compare the detection rates of X-ray,ultrasound,computed tomography(CT)and cone beam CT(CBCT)for submandibular gland calculi in different positions,and to explore the auxiliary value of 3-dimensional visualization technology in diagnosis and treatment of submandibular gland calculi.Methods The X-ray,ultrasound,CT and CBCT examination data of 113 patients with submandibular gland calculi at General Hospital of Ningxia Medical University from Nov.2014 to Mar.2021 were retrospectively analyzed.The detection rates and overall detection rates of the 4 imaging methods for calculi in different positions were compared.Mimics 19.0 software and CBCT data were used for 3D reconstruction imaging,visually displaying the location,size,morphology,and number of calculi from a visual perspective.Results There was no significant difference in the total detection rate of submandibular gland calculi between CBCT and CT(98.2％[111/113]vs 95.6％[108/113],P＞0.05),but both were significantly higher than that of X-ray(65.5％,74/113)and ultrasound(73.5％,83/113).The detection rates of ultrasound for calculi in the anterior and middle ducts were the lowest(63.6％[21/33]and 72.2％[26/36],respectively),which were significantly different from those of CBCT(97.0％[32/33]and 100.0％[36/36],respectively)and CT(93.9％[31/33]and 97.2％[35/36],respectively)(all P＜0.05).The detection rate of X-ray for calculi in the posterior duct was significantly lower than that of ultrasound,CBCT,and CT(40.9％[18/44]vs 81.8％[36/44],97.7％[43/44],and 95.5％[42/44],all P＜0.01).After CBCT data were imported into Mimics 19.0 software,submandibular gland calculi with different sizes,shapes,or numbers were successfully visualized and reconstructed.The reconstructed image was clear,and anatomical position relationship between the calculi and the mandible was visualized.Conclusion CBCT has good application value in the diagnosis of submandibular gland calculi and can replace traditional CT for the diagnosis of sialolithiasis.Clinically,CBCT examination can be directly performed for accurate diagnosis of calculi in the posterior duct which are not detected by double coincidence diagnosis but are indicated by ultrasound.For calculi in the anterior and middle ducts,X-ray and CBCT are preferred.Visualization technology helps clinical patient education and the development of personalized preoperative treatment plans.

Alzheimer's disease(AD)is a common degenerative disease of the central nervous system in which neuropathological changes precede cognitive dysfunction and behavioral impairment. Currently, early diagnosis of AD is based on invasive and expensive testing techniques that are difficult to use widely in the clinical setting. Therefore, there is an urgent need for new markers to detect AD at an early stage. The eye, as an extension of the brain, has been found to show earlier onset of ocular pathologic changes in patients with AD compared to brain pathologic changes, such as retinal structural abnormalities, visual dysfunction, retinal abnormal protein accumulation, choroidal thickness changes, decreased corneal nerve fiber density, deposition of abnormal Aβ proteins in the lens, and pupillary light decreased sensitivity of response, etc. This article reviews the ocular pathologic changes in AD patients in recent years to provide new ideas for the early clinical diagnosis of AD.