Medical humanities consistently run through the entire process of medical development and educational reform. However， with the increasingly prominent dominance of evidence-based medicine in clinical practice， the medical humanities have gradually been weakened in both medical education and clinical practice. Narrative medicine， through telling and listening to patients’ stories， enhances healthcare professionals’ empathy， fosters doctor–patient communication， and facilitates a return to the humanistic essence of medical education and clinical practice. By sorting out and reviewing related literature and developmental trends both at home and abroad， this paper pointed out the existing structural problem of an imbalance between technological priority and humanistic care in medical education， focusing on how to achieve an effective integration of medical humanities and narrative medicine in medical education. This paper also systematically analyzed the significance of both medical humanities and narrative medicine in the medical education system and proposed promoting the deep embedding of narrative medicine in medical education from three entry points， namely， curriculum integration， interdisciplinary collaboration， and the construction of teaching evaluation systems. The aim was to provide theoretical support and practical experience for medical education reform， foster the coordinated development of professional competence and humanistic spirit among medical talents， and truly achieve the goal of cultivating well-rounded medical talents.

Purpose To investigate the expression of thioredoxin-interacting protein(TXNIP)in placental tissues of gestational diabetes mellitus(GDM)and its role in lipid deposition in the placental trophoblast.Methods The pla-centa tissues of 16 GDM pregnant women and 25 women with normal glucose tolerance(NGT)were collected.Mean-while,in vitro models of high-glucose induced human chorionic trophoblast cells(HTR-8/SVneo)were established,which were divided into normal glucose control group(NG),high glucose group(HG),high glucose+si nonsense in-terference group(HG+siNC)and high glucose+TXNIP siRNA group(HG+siTXNIP).The pathological structure and morphological changes of placenta were observed by HE staining.Lipid droplet formation was detected by oil red O staining.The expression and localization of TXNIP in cells were detected by immunocytochemical EnVision method.The mRNA and protein expression levels of TXNIP and lipogenic protein SREBP1 were detected by real-time fluorescent quantitative PCR and Western blot.The relationships between TXNIP expression and lipid droplet accumulation in-duced by high glucose was analyzed.Results High glucose results in abnormal placental structure of GDM.The area of human chorionic intervillous tissue in placenta of GDM group was decreased,the size of fetal capillaries was different and the lumen was dilated.Compared with those NGT group,the accumulation of lipid droplets and the expression of TXNIP mRNA and protein in placental tissue of GDM were increased(P＜0.05).The TXNIP and SREBP1 were up-regulated and the formation of droplets increased in high glucose induced HTR-8/SVneo cells(P＜0.05).On the con-trary,TXNIP siRNA transfection reversed the gene expression level and lipid deposition in high glucose induced cells(P＜0.05).Conclusion TXNIP is involved in abnormal lipid deposition in the placental trophoblast of GDM.

Purpose To investigate the expression of thioredoxin-interacting protein(TXNIP)in placental tissues of gestational diabetes mellitus(GDM)and its role in lipid deposition in the placental trophoblast.Methods The pla-centa tissues of 16 GDM pregnant women and 25 women with normal glucose tolerance(NGT)were collected.Mean-while,in vitro models of high-glucose induced human chorionic trophoblast cells(HTR-8/SVneo)were established,which were divided into normal glucose control group(NG),high glucose group(HG),high glucose+si nonsense in-terference group(HG+siNC)and high glucose+TXNIP siRNA group(HG+siTXNIP).The pathological structure and morphological changes of placenta were observed by HE staining.Lipid droplet formation was detected by oil red O staining.The expression and localization of TXNIP in cells were detected by immunocytochemical EnVision method.The mRNA and protein expression levels of TXNIP and lipogenic protein SREBP1 were detected by real-time fluorescent quantitative PCR and Western blot.The relationships between TXNIP expression and lipid droplet accumulation in-duced by high glucose was analyzed.Results High glucose results in abnormal placental structure of GDM.The area of human chorionic intervillous tissue in placenta of GDM group was decreased,the size of fetal capillaries was different and the lumen was dilated.Compared with those NGT group,the accumulation of lipid droplets and the expression of TXNIP mRNA and protein in placental tissue of GDM were increased(P＜0.05).The TXNIP and SREBP1 were up-regulated and the formation of droplets increased in high glucose induced HTR-8/SVneo cells(P＜0.05).On the con-trary,TXNIP siRNA transfection reversed the gene expression level and lipid deposition in high glucose induced cells(P＜0.05).Conclusion TXNIP is involved in abnormal lipid deposition in the placental trophoblast of GDM.

With the establishment of bio-psycho-social medical model,both social and psychological factors play an important role in the occurrence,development and treatment of diseases.Hypertension is a common chronic multiple disease in China,and patients are often complicated with depression and other e-motional disorders.The interaction between hypertension and depression significantly increases the risk of poor prognosis.Current studies have shown a bidirectional promoting relationship between hypertension and depression,and they have some com-mon pathogenesis.However,the specific mechanism of their co-morbidity has not been fully elucidated.Renin-angiotensin sys-tem(RAS)plays an important role in the regulation of hyperten-sion and depression and other emotions.It is composed of two antagonistic pathways.The balance is maintained by angioten-sin-converting enzyme 2(ACE2).Therefore,this article reviews the relationship and mechanism of RAS in hypertension,depres-sion and comorbid states,in order to provide new treatment ide-as for hypertension and depression.

Objective:To investigate the survival outcomes and prognostic factors of patients with double primary breast cancer (BC) and endometrial cancer (EC).Methods:A retrospective cohort study was conducted using data for the period 1992-2018 from the Surveillance, Epidemiology, and End Results (SEER) database. There were 3 465 patients with BC as the first primary cancer (BC-EC group) and 2 804 patients with EC as the first primary cancer (EC-BC group). Kaplan-Meier analysis and cumulative incidence function were used to estimate overall mortality, breast cancer-specific mortality, and endometrial cancer-specific mortality, respectively. Cox regression and Fine-Gray regression were used to analyze the prognostic factors of overall mortality, breast cancer-specific mortality, and endometrial cancer-specific mortality, respectively.Results:During a median follow-up of 160 months, 1 616 deaths occurred in the BC-EC group, with EC being the leading cause of death (37.69%); 994 deaths occurred in the EC-BC group, with BC being the leading cause of death (28.77%). Cox regression identified patients with older ages at first primary cancer diagnosis (54-61 years: HR=1.46, 95% CI: 1.26-1.69; 62-68 years: HR=2.64, 95% CI: 2.29-3.03; ≥69 years: HR=4.89, 95% CI: 4.27-5.60), shorter time interval between the diagnoses (0-5 months: HR=6.13, 95% CI: 5.21-7.21; 6-23 months: HR=5.69, 95% CI: 4.95-6.55; 24-59 months: HR=3.44, 95% CI: 3.04-3.89; 60-119 months: HR=2.32, 95% CI: 2.07-2.59), mixed ductal-lobular BC ( HR=1.29, 95% CI: 1.11-1.48), endometrial mixed cell adenocarcinoma ( HR=1.23, 95% CI: 1.01-1.50), advanced tumor grade (grade Ⅱ BC: HR=1.13, 95% CI: 1.01-1.27; grade Ⅲ BC: HR=1.24, 95% CI: 1.10-1.41; grade Ⅱ EC: HR=1.19, 95% CI: 1.06-1.33; grade Ⅲ EC: HR=1.68, 95% CI: 1.48-1.90), advanced tumor stage of the two cancers (distant BC: HR=3.14, 95% CI: 2.50-3.94; regional EC: HR=1.53, 95% CI: 1.36-1.71; distant EC: HR=3.00, 95% CI: 2.59-3.47) had increased risk of overall mortality. Fine-Gray regression showed that compared with BC-EC patients, EC-BC patients had a higher risk of breast cancer-specific mortality [sub-distribution hazard ratio (s HR=1.24, 95% CI: 1.04-1.47], but a lower risk of endometrial cancer-specific mortality (s HR=0.37, 95% CI: 0.30-0.46). Older ages at first cancer diagnosis, shorter intervals between the diagnoses, negative ER and PR status, and advanced BC grades/stages were associated with increased breast cancer-specific mortality ( P＜0.05). Similarly, older ages, shorter intervals, endometrial serous carcinoma/mixed cell adenocarcinoma, and advanced EC grades/stages correlated with elevated endometrial cancer-specific mortality ( P＜0.05). Conclusion:The management of double primary BC and EC patients requires multidisciplinary strategies, with particular attention to patients presenting older ages at first cancer diagnosis, shorter intervals between the diagnoses, and unfavorable tumor characteristics.

Background:Bushen Zhuanggu Formula(BZF),derived from the classic Yougui Pills,has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head(NONFH),particularly by promoting bone repair.However,its underlying mechanisms remain unclear.Objective:This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH.Materials and methods:A total of 518 potential BZF targets were identified from the ETCM v2.0 database.Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls.A drug target-disease gene interaction network was constructed to identify candidate BZF targets involved in NONFH pathogenesis.In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH.Results:Network analysis identified key pathways associated with blood circulation obstruction,immune-inflammatory imbalance,and abnormal bone metabolism.Protein kinase C alpha(PKCA),Ras proto-oncogene(RAS),mitogen-activated protein kinase 3(ERK),ETS proto-oncogene 1(ETS1),and receptor activator of nuclear factor-κB ligand(RANKL)formed a signaling axis implicated in NONFH pathogenesis.BZF treatment alleviated joint inflammation,preserved trabecular bone morphology,reduced bone loss,and promoted bone repair.Mechanistically,BZF significantly downregulated the expression of PKCA,RAS,ERK,ETS1,and RANKL,improved blood circulation,and inhibited osteoclast activation while promoting osteoblast activation.Conclusion:BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis,thereby reversing dysregulated bone metabolism.

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVES: This study aimed to investigate the impact of foam macrophages (FMs) on the intracellular survival of Mycobacterium tuberculosis (MTB) and identify the molecular mechanisms influencing MTB survival. METHODS: An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival. RESULTS: Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate (cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival. CONCLUSIONS FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
Mycobacterium tuberculosis/physiology* ; Transcriptome ; Metabolomics ; Foam Cells/microbiology* ; Humans ; Metabolome ; Tuberculosis/microbiology* ; Gene Expression Profiling

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion