Background: and Purpose Bilirubin has potent antioxidant, anti-inflammatory, and neuroprotective effects. Herein, we investigated whether total bilirubin (TBIL) modifies the association between hypertension and cerebral small vessel disease (CSVD). Methods: Data were obtained from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study. TBIL and direct bilirubin (DBIL) levels were assayed using fasting venous blood samples. Indirect bilirubin (IBIL) was calculated by subtracting DBIL from TBIL. TBIL was stratified as ≤17 μmol/L and >17 μmol/L based on the biological relevance of Gilbert’s syndrome. Hypertension was defined as blood pressure ≥140/90 mm Hg, self-reported hypertension history, or current use of antihypertensive agents. White matter hyperintensity, lacunes, cerebral microbleeds, and enlarged perivascular spaces were evaluated using magnetic resonance imaging and used to rate CSVD burden according to the criteria proposed by Wardlaw et al. and Rothwell et al. Results: This study included 3,061 participants, with a mean age of 61.2±6.7 years and 46.5% males. After adjusting for confounders, hypertension was associated with increased odds of presence of CSVD (Wardlaw: odds ratio [OR]=1.86, 95% confidence interval [CI] 1.41–2.44, P<0.001; Rothwell: OR=1.84, 95% CI 1.43–2.38, P<0.001) and higher modified total CSVD burden (common OR: 1.85, 95% CI 1.45–2.36, P<0.001) in participants with TBIL ≤17 μmol/L but not in TBIL >17 μmol/L (P for interaction <0.05). Johnson–Neyman analyses showed cut-off concentrations of 22.3–22.4 μmol/L for effect modification by TBIL. IBIL contributed to effect modification, whereas DBIL did not. Conclusions Mildly elevated TBIL may modify the association between hypertension and CSVD.

With the rapid advancement of medical technology and the increasing complexity of clinical environments, competence in clinical ethical decision-making has become an indispensable core competency for exemplary physicians. However, traditional medical ethics education has long been confronted with the persistent challenges of theory-practice dissociation and the disconnect between pedagogical settings and clinical realities. Thus, how to construct a "Clinical Ethics" curriculum that aligns with the objectives of training high-caliber medical professionals has emerged as a critical and challenging issue in current medical education reform. To effectively address this challenge, the Office of Education at Peking University Third Hospital, since 2021, has assembled a multidisciplinary "Clinical Ethics" teaching and management team comprising faculty from Peking University School of Humanities and key clinical specialists from the hospital. In 2022, the "Clinical Ethics" elective course was formally launched for fourth-year students in the eight-year MD program who had completed coursework in "Medical Ethics" and organ-system-based curricula, with the aim of exploring and operationalizing a pre-clinical ethics education model tailored for senior medical students. The course employs a modular instructional design encompassing "theoretical review-case-based deliberation-clinical workshop", which effectively facilitates the deep integration of medical humanities with clinical practice.Following four years of iterative refinement through the "plan-act-observe-reflect" cycle, the course has demonstrated positive outcomes in enhancing students' ethical awareness and decision-making capabilities, and has preliminarily established a sustainable collaborative mechanism among the multidisciplinary faculty team. This article systematically delineates the course development background, pedagogical model and methodological innovations, and the multidisciplinary collaborative framework, alongside reflections and summaries based on implementation outcomes, with the intent of providing references for the future development of "Clinical Ethics" curricula.

Objective To explore the deeper understanding of the pregnancy and delivery experience of three-child pregnant and matemal women,and to provide a basis for healthcare personnel to provide more systematic,safe,and targeted perinatal healthcare services and care measures for three-child pregnant and matemal women.Methods Purposive sampling method was used to select 17 cases of three-child pregnant and matemal women who were admitted and delivered in a tertiary level-A matemal and child healthcare hospital in Nanjing from August 2022 to June 2023 for semi-structured interviews,and Colaizzi 7-step process of analyzing,summarizing,and refining the themes was used.Results A total of 4 themes were extracted,including determination of willingness to become pregnant,perceived risks of childbirth,perceived benefits to themselves and their families,diversified support needs.Conclusion The establishment of pregnancy intention of three-child pregnant women is affected by many factors.Relevant departments should actively implement the supporting measures of the three-child birth policy;healthcare workers should strengthen perinatal healthcare services for three-child mothers to reduce the risk of giving birth,actively strengthen their sense of benefits related to pregnancy,and establish a whole process of support system to promote the health of mothers and infants.

Objective To observe the effect of mild moxibustion at"Qihai","Guanyuan"and"Zhongji"on GnRH and its receptor in rats with gynecological cold coagulation and blood stasis syndrome(CCBS);To explore the mechanism of moxibustion on reproductive function of gynecological CCBS.Methods Totally 48 female SD rats were randomly divided into blank group,model group,moxibustion group,inhibitor group,inhibitor+moxibustion group and angonist group,with 8 rats in each group.The gynecological CCBS model was prepared by ice bath and adrenalin injection.GnRHant or GnRHa injection and mild moxibustion intervention were given to each treatment group.The score of CCBS symptoms and the amount of microcirculation blood perfusion in uterus were detected,the morphology of ovarian tissue and uterine tissue were observed by HE staining,serum reproductive hormones(GnRH,FSH,LH)and neurotransmitters(DA,GABA)contents were detected by ELISA,the expressions of GnRHR,FSHR and LHR mRNA and protein in ovarian and uterine tissue were detected by immunohistochemistry,RT-qPCR and Western blot.Results Compared with the blank group,the symptom score of CCBS in model group was significantly increased,the amount of microcirculation blood perfusion in uterus was decreased,the ovarian follicles were decreased,and the endometrial epithelium was thinner and the structure was chaotic,the contents of serum GnRH,FSH,LH,GABA decreased,DA content increased;the mRNA and protein expressions of GnRHR,FSHR and LHR in ovarian tissue decreased(P<0.01).Compared with the model group,the symptom score of CCBS in each intervention group were significantly decreased,the amount of microcirculation blood perfusion in uterus increased,ovarian follicles increased,endometrium thickened and glands increased,the contents of serum GnRH,FSH,LH,GABA increased,DA content decreased;the mRNA and protein expressions of GnRHR,FSHR and LHR were increased(P<0.05,P<0.01).Conclusion Moxibustion can regulate GnRH and its receptor and improve HPO axis function by regulating neurotransmitters,so as to improve the general state and reproductive function of gynecological CCBS model rats.

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of MED15-TFE3 gene fusion renal cell carcinoma (MED15-TFE3 RCC).Methods:A total of 12 MED15-TFE3 RCCs, diagnosed from 2016 to 2023, were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China for clinicopathologic, immunohistochemical, fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq) analyses and follow-up. In addition, its diagnosis and differential diagnosis were also explored.Results:There were five males and seven females. The patients′ ages ranged from 16 to 60 years, with an average age of 40.4 years. The follow-up time ranged from 15 to 92 months, and no recurrence or metastasis was observed. Histologically, 6 cases exhibited extensive cystic structures with almost no solid sheet components, while the remaining 6 cases displayed a cysto-solid growth pattern. The cytoplasm of the tumor cells appeared flocculent, with a clear or faintly eosinophilic appearance, and nucleoli were inconspicuous. Psammoma bodies were observed in 12 cases. There was deposition of basement membrane-like material in 5 cases. All cases showed strong expression of TFE3, GPNMB, Cathepsin K, Melan A, and PAX8, while no expression of CAⅨ or CK7. FISH analyses showed that all 12 cases were positive for the MED15-TFE3 fusion, while the MED15-TFE3 fusion gene and specific fusion sites were detected in 2 cases using RNA-seq.Conclusions:MED15-TFE3 RCC is a type of TFE3-rearranged renal cell carcinoma that exhibits both identifiable diagnostic characteristics and highly deceptive morphology. Its distinct extensive cystic structure can be easily confused with multilocular cystic renal neoplasm of low malignant potential, necessitating careful differentiation in routine practice.

Objective:To analyze the association between osteoporosis and the risk for Alzheimer's disease (AD).Methods:A total of 471 922 study subjects were selected from the UK Biobank database, including 12 818 osteoporosis cases and 459 104 controls. Cox proportional hazard regression model and competing risk model were used to evaluate the association between osteoporosis and AD after adjusting confounding factors. Furthermore, a Mendelian randomization (MR) study was conducted by using the data of two published genome-wide association studies, and 1 050 highly relevant single nucleotide polymorphisms were identified from the bone mineral density data as instrumental variables. The association between bone mineral density and the risk for AD was evaluated by using inverse variance weighted method, MR-Egger regression, and weighted median estimator method. Additionally, sensitivity analyses were performed.Results:After adjusting for confounders, no significant association between osteoporosis and an increased risk for AD was found in the cohort study (Cox proportional hazard regression model analysis: HR=1.10, 95% CI: 0.78-1.56, P=0.588). The MR analysis revealed no association between bone mineral density and the risk for AD (inverse-variance weighted: OR=1.03, 95% CI: 0.98-1.09, P=0.252), and the results remained robust in multiple sensitivity analyses. Conclusion:The study result does not support the association between osteoporosis and risk for AD.

Human Respiratory Stem Cells (RSCs) play a crucial role in the maintenance, repair and regeneration of the respiratory system. As a novel therapeutic method, stem cell therapy is a popular research direction in the medical field. And with the in-depth research on the mechanism of pneumonia caused by respiratory infections in recent years, the use of RSCs to explore pneumonia caused by respiratory infections and its therapeutic strategies has become a hot topic. In this paper, we firstly outlined the types of RSCs, summarized the mechanism of pneumonia caused by respiratory tract infections, discussed the advantages of RSCs application and the progress of culture differentiation, and elaborated the therapeutic exploration of RSCs in pneumonia caused by respiratory tract infections.

Objective To investigate the comparative neuroprotective effects of human umbilical cord mesenchymal stem cells(hUC-MSCs-Exos)administered via different routes on hypoxic ischemic brain damage(HIBD)in neonatal mice.Methods Healthy one-week-old SPF-grade BALB/c mice were randomly divided into 4 groups:sham operation group(n=6),model group(n=6),exosome group 1(n=8),exosome group 2(n=8).HIBD was induced using the Rice-Vannucci method.Exosome group 1 and Exosome group 2 were intraperitoneal injection/intranasal drip of phosphate buffer(PBS)100 μl containing 10 μl exosomes within 24 h after successful modeling,respectively.Sham operation and model groups were intraperitoneal injection of PBS 100 μl.On the 7th day after the intervention,neuromotor function was assessed using the horizontal grid test and pole climbing test.On the 2nd day after the evaluation,all mice were killed and their brains were removed by decapitation.HE staining was used to observe the pathological injury of brain tissue,toluidine blue staining was used to observe the survival of neurons in cerebral cortex,and TUNEL staining was used to observe the apoptosis of cerebral cortex cells.Results Compared with sham operation group,model group,exosome group 1 and exosome group 2 exhibited increased hind limb drops in horizontal grid test and climbing scores(P<0.05).No significant difference was found in model group,exosome group 1 and exosome group 2 in these measures(P<0.05).Significant pathology was observed in model group,exosome group 1 and exosome group 2 compared to sham operation group(P<0.05),with significantly reduced damage in exosome group 1 and exosome group 2 compared to model group(P<0.05).Compared with sham operation group,Nissl body count was lower in model group and exosome group 1 and exosome group 2,with a higher count in exosome group 2 compared to exosome group 1(P<0.05).Compared with sham operation group,apoptotic cells were higher in model group and exosome group 1 and exosome group 2,with a significant reduction in exosome group 1 and exosome group 2 compared to model group,and the lowest in exosome group 2(P<0.05).Conclusions hUC-MSCs-Exos can improve the neuronal motor function,promote neuron repair and inhibit apoptosis in HIBD mice.Intranasal administration of hUC-MSCs-Exos is more effective than intraperitoneal administration for reducing neuronal apoptosis in HIBP neonatal mice,offering a convenient and rapid method suitable for clinical application.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome