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.

ObjectiveFrozen shoulder (FS) is a debilitating musculoskeletal disorder characterized by persistent inflammation and progressive fibrosis of the glenohumeral joint capsule, leading to pain and severely restricted range of motion. Given the limited efficacy of current pharmacotherapies, there is an urgent need for novel anti-fibrotic agents. Guyanxiao Tincture (GYX), a traditional Chinese herbal formula, has shown clinical benefits in alleviating FS symptoms. However, its bioactive constituents and the molecular mechanisms underlying its therapeutic effects remain poorly defined. This study aimed to systematically evaluate the therapeutic efficacy of GYX against FS and to elucidate the mechanisms by which GYX attenuates capsular fibrosis. MethodsA Sprague-Dawley (SD) rat model of FS was established by immobilizing the unilateral shoulder with a plaster cast for 21 d. Following model induction, animals were administered with GYX or its serum-identified bioactive component, icariside F2. The absorbed prototype compounds of GYX in FS rat serum were profiled using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Therapeutic effects were assessed by measuring shoulder range of motion (ROM), histopathological evaluation of the capsule via hematoxylin-eosin staining, and quantification of transforming growth factor‑β1 (TGF-β1) content by ELISA. To explore the underlying mechanisms, transcriptomic profiling of the shoulder capsule was performed using RNA sequencing, and differentially expressed genes were validated by real-time quantitative PCR. Protein expression and localization were examined through immunohistochemistry, immunofluorescence, and Western blot. Protein-protein interaction networks were constructed to identify key regulatory hubs. In vitro, primary shoulder capsule fibroblasts were stimulated with TGF‑β1 to induce a fibrotic phenotype and then treated with icariside F2. The expression of alpha cardiac muscle 1 (ACTC1), α‑smooth muscle actin, and collagen I was subsequently measured. ResultsSerum pharmacochemistry analysis identified icariside F2 as the predominant circulating bioactive component of GYX in FS rats. Both GYX and icariside F2 treatment significantly improved the ROM and ameliorated histopathological lesions, including the attenuation of synovial hyperplasia, inflammatory infiltration, and excessive collagen deposition in the shoulder capsule. Consistently, elevated TGF‑β1 levels in the model group were markedly reduced after the interventions. RNA sequencing revealed that actin ACTC1 was dramatically upregulated in the fibrotic capsule, accompanied by the enrichment of fibrosis-associated pathways such as TGF‑β signaling, focal adhesion, and ECM-receptor interaction. Protein-protein interaction network analysis demonstrated that ACTC1 directly interacts with core fibrotic genes, including Col1a1, Col1a2, Thbs2, and Fn1. Critically, icariside F2 administration significantly reversed the aberrant overexpression of ACTC1 and suppressed the activation of the aforementioned fibrosis-related pathways in vivo. In TGF‑β1-stimulated fibroblasts, icariside F2 dose-dependently downregulated ACTC1 at both the mRNA and protein levels and concurrently decreased the expression of the fibrotic markers α‑smooth muscle actin and collagen I. Immunofluorescence and Western blot further confirmed that icariside F2 attenuated stress fiber formation and collagen production in vitro. ConclusionGYX and its bioactive component icariside F2 effectively alleviate the progression of frozen shoulder by inhibiting capsular fibrosis. Mechanistically, the therapeutic action is functionally linked to the suppression of ACTC1 and its downstream profibrotic signaling cascade, highlighting ACTC1 as a promising therapeutic target for the management of frozen shoulder.

Objective To explore the characteristics and prognosis of follicular lymphoma(FL)with bulky disease under rituximab-based first-line treatment.Methods A retrospective analysis was conducted on 525 FL patients diagnosed between September 2009 and September 2021 who received rituximab as a first-line treat-ment[342 patients received rituximab combined with chemotherapy(R-chemo),183 patients received rituximab plus lenalidomide(R2)].The clinicopathologic characteristics,gene mutations,and prognosis of bulky FL patients were analyzed.Results Compared to non-bulky FL patients,bulky FL patients had a significantly higher proportion of lymph node≥5 sites,≥2 extranodal involvement,bone marrow involvement,elevated LDH,and a higher proportion in the high-risk group of FLIPI1 and FLIPI2.Gene sequencing revealed a significantly higher mutation rate of ZNF608 in bulky FL patients compared to non-bulky FL patients.In patients receiving R-chemo as the first-line treatment,there was no significant difference in progression-free survival(PFS)and overall survival(OS)between bulky and non-bulky FL patients.However,in patients treated with R2,the PFS and OS of bulky FL patients was significantly shorter.Conclusions Bulky FL patients compared to non-bulky FL patients have a significantly higher proportion of high-risk baseline characteristics.For bulky FL at diagnosis,chemo-free regimens require further exploration on the basis of R2.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Objective:To explore the clinical symptoms, imaging characteristics, cerebrospinal fluid (CSF) features, as well as the treatment and prognosis of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.Methods:Sixty-one patients with anti-GFAP astrocyte antibody (GFAP-IgG) single-positive autoimmune encephalitis who were treated at the Third Affiliated Hospital, Sun Yat-sen University between January 2017 and September 2023 were retrospectively collected. The demographic characteristics (age at onset, sex), clinical symptoms (core symptoms, neurological deficits, psychiatric behavioral abnormalities, and autonomic dysfunction), imaging features [brain/spinal cord/optic nerve magnetic resonance imaging (MRI) lesion distribution and enhancement patterns], and CSF parameters were analyzed. Acute-phase treatments, including methylprednisolone pulse therapy, intravenous immunoglobulin (IVIG), etc, along with the follow-up outcomes [modified Rankin Scale (mRS) score] were recorded.Results:The onset age was 40 (30, 55) years, and 68.9% (42/61) of the patients were male. The most common clinical manifestations were fever (65.6%, 40/61), headache (60.7%, 37/61), and urinary/defecatory abnormalities (45.9%, 28/61). Brain MRI revealed lesions predominantly in the cerebral cortex and subcortical white matter (57.4%, 35/61), periventricular white matter (50.8%, 31/61), and basal ganglia (36.1%, 22/61). Periventricular linear-radiating enhancement was the predominant MRI enhancement pattern (55.7%, 34/61). Spinal MRI showed lesions mainly in the cervical (42.6%, 26/61) and thoracic spinal cord (32.8%, 30/61), with leptomeningeal enhancement (31.1%, 19/61) and scattered punctate/patchy enhancements (21.3%, 13/61). Optic neuropathy was observed in 6 cases (9.8%). CSF analysis demonstrated a pressure of 180 (133, 240) mmH 2O (1 mmH 2O=0.009 8 kPa), white blood cell count of 29 (4, 156)×10?/L, and protein level of 0.72 (0.40, 1.44) g/L. Nineteen patients (31.1%) experienced rapid progression of meningoencephalitis or myelitis within 3 days of admission. All patients received methylprednisolone pulse therapy, with 47.5% (29/61) additionally treated with IVIG. At a follow-up of 12 (3, 28) months, 12 cases (19.7%) relapsed, and 75.4% (46/61) had favorable outcomes (mRS score 0-2). Poor prognosis (mRS score>2) was observed in 4 cases, including 3 with cervical spinal cord involvement and status epilepticus, 1 elderly patient with lung cancer. Conclusions:GFAP astrocytopathy predominantly affects young adults, with a male predominance. Spinal cord involvement is common, manifesting as myelitis and myelopathy. Rapid progression of meningoencephalitis or myelitis may occur early in the disease course. Periventricular linear-radiating enhancement on brain MRI is a key diagnostic clue. Leukocyte and protein levels in the cerebrospinal fluid are generally mildly to moderately elevated. Most patients respond well to corticosteroids and immunotherapy, with favorable outcomes. However, advanced age and cervical spinal cord involvement are associated with poor prognosis.

Objective:To investigate the influence and mechanisms of metformin on the proliferation and apoptosis of human keloid fibroblasts (Fbs).Methods:This study was an experimental research. The keloid tissue was collected from 7 keloid patients (2 males and 5 females, aged 20-65 years, with a disease course of more than 1 year) who underwent keloid excision surgery at the Department of Plastic, Cosmetic and Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from September 2020 to September 2023. The primary Fbs were isolated and cultured, and cells from passages 3 to 6 were used for experiments. The cells were divided into control group and metformin group, and were cultured in complete medium. The medium for metformin group was supplemented with metformin at a final molarity of 60 mmol/L. The cell counting kit-8 was used to assess the proliferation activity of cells in two groups after 12 and 24 hours of culture, and the proliferation inhibition rate of cells in metformin group after 12 and 24 hours of culture was calculated, with a sample size of 6. The apoptosis detection kit was used to detect the apoptotic distribution of cells in control group after 0 hour (immediately) of culture and in metformin group after 12 and 24 hours of culture, with a sample size of 3. The cell cycle detection kit was used to detect the cycle distribution of cells in two groups after 12 and 24 hours of culture, with a sample size of 3. The eukaryotic mRNA sequencing was performed on suitable number of cells of two groups after 24 hours of culture, and the Kyoto encyclopedia of genes and genomes functional annotation analysis and functional enrichment analysis were performed after screening for differentially expressed genes (DEGs) with significantly differential expression between two groups. Western blotting was conducted to detect the protein expressions of phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR) in the PI3K/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway of cells in two groups after 24 hours of culture, with a sample size of 3.Results:After 12 and 24 hours of culture, the proliferation activity of cells in metformin group was significantly lower than that in control group (with t values of 4.70 and 24.02, respectively, P<0.05); the proliferation activity of cells in metformin group after 24 hours of culture was significantly lower than that after 12 hours of culture within the group ( t=4.73, P<0.05). Compared with that after 12 hours of culture within the group, the proliferation inhibition rate of cells in metformin group was significantly increased after 24 hours of culture ( t=5.29, P<0.05). Compared with that in control group after 0 hour of culture, the proportion of early apoptotic cells in metformin group was significantly increased (with t values of 6.62 and 4.58, respectively, P<0.05), and the proportion of early and late apoptotic cells was significantly increased after 12 and 24 hours of culture (with t values of 4.84 and 3.75, respectively, P<0.05). After 24 hours of culture, the proportion of late apoptotic cells in metformin group was significantly higher than that after 12 hours of culture within the group ( t=4.55, P<0.05). After 12 hours of culture, the proportion of S-phase cells in metformin group was significantly lower than that in control group ( t=5.90, P<0.05). After 24 hours of culture, compared with that in control group, the proportion of G0/G1-phase cells in metformin group was significantly increased ( t=5.36, P<0.05), while the proportion of G2/M-phase cells was significantly decreased ( t=17.63, P<0.05). The proportion of S-phase cells in metformin group after 24 hours of culture was significantly higher than that after 12 hours of culture within the group ( t=7.60, P<0.05). After 24 hours of culture, 4 814 DEGs with significantly differential expression were detected in the cells of metformin group compared with control group. The significantly upregulated and downregulated DEGs were mainly involved in biological functions related to signal transduction, cell growth and death, transport and catabolism, the endocrine system, the immune system, and cancer. The pathways that were significantly enriched with DEGs with significantly differential expression included the cell cycle and DNA replication, with the highest number of genes in the PI3K/Akt signaling pathway. After 24 hours of culture, the protein expressions of PI3K, p-Akt, and p-mTOR of cells in metformin group were 0.190±0.017, 0.170±0.017, and 0.247±0.005, respectively, which were significantly lower than 0.440±0.026, 0.300±0.060, and 0.547±0.025 in control group (with t values of 13.69, 3.61, and 20.12, respectively, P values all <0.05). Conclusions:Metformin can significantly inhibit the proliferation of human keloid Fbs through the PI3K/Akt/mTOR signaling pathway and effectively induce its apoptotic process, thereby exerting antifibrotic effects.

Aim To explore the mechanism of luteolin in alleviating hepatic fibrosis.Methods C57BL/6 mice were randomly divided into the control group,CCl4 group,silybin group(100 mg·kg-1)and luteo-lin group(100 mg·kg-1).After 10-week modeling and 2-week treatment,the serum levels of aminotrans-ferase and liver histopathology were examined.Hepatic fibrosis and autophagy-related gene expression were as-sessed using immunohistochemistry and immunofluores-cence.Human hepatic stellate cell line(LX2)was cultured and divided into control,TGF-β1(10 mg·L-1),TGF-β1+silybin(40 μmol·L-1),TGF-β1+luteolin(40 μmol·L-1).Fibrotic and autophagy-re-lated markers were analyzed using quantitative real-time PCR,Western blot,immunofluorescence and MDC staining.Results Compared with the CCl4 group,the treatment groups showed significantly improved liver function and reduced hepatic fibrosis,with markedly downregulated COL1A1 and α-SMA expression,and luteolin demonstrated superior efficacy.Compared with TGF-β1 group,luteolin treatment significantly de-creased mRNA levels of COL1A1,ACTA2 and MAP1LC3B,while increasing the mRNA level of SQSTM1,the protein levels of COL1A1 and α-SMA de-creased,p62 was enhanced,the LC3Ⅱ/Ⅰ ratio was downregulated,and autophagy was reduced.These effects of luteolin were reversed by autophagy inducer rapamycin.Conclusion Luteolin alleviates liver fi-brosis by decreasing the autophagy of hepatic stellate cells.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

Soy is a vital source of plant carbohydrates.However,it poses significant allergenic risks,particularly to young children and animals.Among the various proteins in soy,β-conglycinin,which con-stitutes approximately 30％of total soy carbohydrates,is a primary allergen.Undigested β-conglycinin can lead to intestinal damage by inhibiting cell growth,disrupting the cytoskeleton,and inducing apopto-sis.It can also enter the lymphatic and circulatory systems,triggering allergic reactions.Conventional ELISA methods for detecting β-conglycinin rely on polyclonal or monoclonal antibodies,which are limited by their large molecular weight,difficulty in accessing the protein core,and sensitivity to acidic and bas-ic conditions.To address these limitations,this study aimed to develop nanobodies(Nbs)against β-con-glycinin.Nbs,derived from the variable regions of heavy-chain antibodies found in camelids,have a mo-lecular weight approximately one-tenth that of conventional antibodies.They offer advantages such as small size,stable structure,high specificity,and strong affinity.A female alpacas was immunized five times using β-conglycinin,which showed a heavy chain antibody potency of 1∶16 000 by ELISA.Pe-ripheral blood lymphocytes were subsequently isolated and total RNA was extracted.The variable region of the heavy-chain antibody was amplified via PCR,and recombinant plasmids were constructed and transformed into the E.coli competency strain ER2738.The resulting library contained about 3.5×108 CFU/mL,which increased to 1.15×1012 PFU/mL after phage rescue,with a 100％Nbs gene insertion rate,indicating high diversity.Its Nbs phage output was significantly enriched by four rounds of solid-phase elution with an enrichment rate of 155.9.Four rounds of solid-phase panning yielded 35 positive clones,all of which shared the same amino acid sequence upon sequencing.The selected Nb was ex-pressed in a prokaryotic system,and its binding ability to β-conglycinin was confirmed using Western blotting and ELISA.The results demonstrated excellent specificity and affinity.This research lays the groundwork for developing a rapid and efficient detection method for β-conglycinin using Nbs,potentially enhancing food safety and allergen management.

Perceptual decision making refers to the process by which individuals make choices and judgments based on sensory information, serving as a fundamental ability for human adaptation to complex environments. While traditional research has focused on perceptual decision making in isolated contexts, growing evidence highlights the profound influence of social contexts prevalent in real-world scenarios. As a crucial factor supporting individual survival and development, social context not only provides rich information sources but also shapes perceptual decision making through top-down processing mechanisms, prompting researchers to recognize the inherently social nature of human decisions. Empirical studies have demonstrated that social information, such as others’ choices or group norms, can systematically bias individuals’ perceptual decisions, often manifesting as conformity behaviors. Social influence can also facilitate performance under certain conditions, particularly when individuals can accurately identify and adopt high-quality social information. The impact of social context on perceptual decisions is modulated by a variety of external and internal factors, including group characteristics(e.g., group size, response consistency), attributes of peers (e.g., familiarity, social status, distinctions between human and artificial agents), as well as individual differences such as confidence, personality traits, and developmental stage. The motivations driving social influence encompass three primary mechanisms: improving decision accuracy through informational influence, gaining social acceptance through normative influence, and maintaining positive self-concept. Recent computational approaches have employed diverse theoretical frameworks to provide valuable insights into the cognitive mechanisms underlying social influence in perceptual decision making. Reinforcement learning models demonstrate how social feedback shapes future choices through reward-based updating. Bayesian inference frameworks describe how individuals integrate personal beliefs with social information based on their respective reliabilities, dynamically updating beliefs to optimize decisions under uncertainty. Drift diffusion models offer powerful tools to decompose social influence into distinct cognitive components, allowing researchers to differentiate between changes in perceptual processing and shifts in decision criteria. Collectively, these models establish a comprehensive methodological foundation for disentangling the multiple pathways by which social context shapes perceptual decisions. Neuroimaging and electrophysiological studies provide converging evidence that social context influences perceptual decision making through multi-level neural mechanisms. At early perceptual processing stages, social influence modulates sensory evidence accumulation in parietal cortex and directly alters primary visual cortex activity, while guiding selective attention to stimulus features consistent with social norms through attentional alignment mechanisms. At higher cognitive levels, the reward system (ventral striatum, ventromedial prefrontal cortex) is activated during group-consistent decisions; emotion-processing networks (anterior cingulate cortex, insula, amygdala) regulate experiences of social acceptance and rejection; and mentalizing-related brain regions (dorsomedial prefrontal cortex, temporoparietal junction) support inference of others’ mental states and social information integration. These neural circuits work synergistically to achieve top-down multi-level modulation of perceptual decision making. Understanding the mechanisms by which social context shapes perceptual decision making has broad theoretical and practical implications. These insights inform the optimization of collective decision-making, the design of socially adaptive human-computer interaction systems, and interventions for cognitive disorders such as autism spectrum disorder and anorexia nervosa. Future studies should combine computational modeling and neuroimaging approaches to systematically investigate the multi-level and dynamic nature of social influences on perceptual decision making.