Clinical reasoning is a core competency in the cultivation of competent medical professionals, requiring practitioners to integrate professional knowledge, clinical experience, and individual patient variability to make sound judgments and therapeutic decisions under conditions of incomplete information, uncertain evidence, and multiple treatment options. Traditional assessment modalities—including written examinations, case analyses, and the objective structured clinical examination (OSCE)—can effectively evaluate learners′ theoretical knowledge and fundamental clinical skills, yet they have limited capacity to capture the dynamic reasoning processes deployed in complex clinical scenarios. The script concordance test (SCT) offers a novel approach to address this gap. Grounded in script theory, the SCT presents typical clinical situations with inherent uncertainty, examining learners′ abilities to interpret new information and their adjustments in diagnostic hypotheses, test selection, and treatment decisions. Responses are scored by comparison with a reference panel of experts using a weighted scoring system, thereby assessing the degree of concordance between the learner′s clinical reasoning and expert patterns. The SCT authentically mirrors real-world clinical decision-making logic, is applicable across various specialties and training stages, and demonstrates particular strength in formative assessment by facilitating early identification of learners′ thinking patterns and potential deficiencies in information analysis, hypothesis revision, and risk-benefit balancing. At present, the application of SCT in Chinese clinical medical education remains in its preliminary stages. Future efforts should focus on developing standardized SCT item banks and feedback mechanisms tailored to the domestic educational context, and incorporating artificial intelligence-assisted technologies to enhance instructional feedback, thereby improving the effectiveness of clinical reasoning training and the overall quality of medical education.

Objective To propose a framework for risk assessment and stepwise management of pulmonary nodules based on existing guidelines and key studies, and to clarify the boundaries for triage, workup escalation, and referral in different detection scenarios. Methods A problem-oriented evidence synthesis approach was used, prioritizing Chinese expert consensus, Fleischner Society Guidelines, British Thoracic Society (BTS) Guidelines, and Lung-RADS. This was supplemented by studies on risk models, imaging measurements, liquid biopsy, tissue sampling, and surgical treatments. This paper is not presented as a formal consensus or a validated clinical pathway. Results A three-tiered framework consisting of basic non-invasive assessment, advanced assessment, and invasive diagnosis was established. It specified the applicable populations, boundaries for the use of risk models, imaging review, management of conflicting results, evaluation of histopathological consistency, and post-intervention follow-up. Liquid biopsy, genetic testing, and artificial intelligence were defined as investigational or adjunctive tools. Conclusion This framework can serve as a preliminary reference for multidisciplinary teams in developing local protocols. It cannot replace applicable guidelines, pathological diagnosis, shared decision-making with patients, or real-world validation.

Objective:To compare the short-term clinical outcomes of thoracoscopy-assisted minimally invasive mitral valve surgery(minimally invasive cardiac surgery MICS group)versus conven-tional median sternotomy mitral valve surgery(conventional surgery group),including surgical metrics,postoperative complications,transfusion volume,and in-hospital mortality rate.Methods:A ret-rospective analysis was performed for 141 patients who underwent mitral valve surgery in Chongqing General Hospital from January 2021 to June 2022,and these patients were divided into MICS group with 42 patients and conventional surgery group with 99 patients.Propensity score matching at a ratio of 1∶1 was performed to ob-tain 82 patients,with 41 patients in each group,and related data were collected and compared,including surgical procedure,cardiopul-monary bypass time,postoperative ventilation time,transfusion volume,and in-hospital mortality.Results:There were no significant differences between the MICS group and the conventional surgery group in sex,age,cardiac functional grading,and comorbidity with diabetes or hypertension,and as for the surgical procedure,there was no significant difference between the two groups in the number of patients undergoing atrial fibrillation radiofrequency ablation(11/42 vs.26/99,P=0.583)or tricuspid valvuloplasty(14/42 vs.39/99,P=0.310).Compared with the conventional surgery group,the MICS group had significantly longer aortic cross-clamp time[(122±48)min vs.(91±50)min,P=0.031]and cardiopulmonary bypass time[(180±73)min vs.(136±72)min,P=0.033],while there was no significant difference in postoperative ventilation time between the two groups after surgery[18.6(12.0,36.2)h vs.24.0(15.5,33.1)h,P=0.265].There was no significant difference in the number of patients with acute renal failure after surgery between the MICS group and the conventional surgery group[grade 1:3(42)vs.7(99);grade 2:0(42)vs.2(99);grade 3:1(42)vs.9(99);P=0.398].There was also no significant difference in the number of patients receiving hemodialysis after surgery between the two groups[1(42)vs.4(99),P=0.531].The MICS group had a significantly lower postoperative transfusion volume than the conventional surgery group[120(80,240)mL vs.400(200,600)mL,P=0.002],and there was no significant difference in in-hospital mortality rate between the two groups[1(42)vs.2(99),P=0.665].After propensity score matching,there were no significant differences between the two groups in general characteristics(sex,age,and comorbidities).Compared with the conventional surgery group,the MICS group had longer cardiopulmonary bypass time[(165±73)min vs.(122±74)min,P=0.053]and aortic cross-clamp time[(119±48)min vs.(98±52)min,P=0.073]and a significantly lower postoperative transfusion volume[120(80,240)mL vs.400(200,600)mL,P<0.001].There were no significant differences between the two groups in 30-day in-hospital mortality rate and postoperative compli-cations(including acute renal failure and requirement for hemodialysis).Conclusion:Thoracoscopy-assisted minimally invasive mitral valve surgery has comparable short-term clinical outcomes and safety to conventional sternotomy.Although MICS requires longer cardiopulmonary bypass time and aortic cross-clamp time,it has relatively low requirements for postoperative transfusion and shows favorable clinical outcomes.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Objective To propose a novel method based on three-dimensional depthwise separable convolution network(3D DSN)for the separation of PET images with dual tracers of 18F-FDG and 18F-FAPI.Methods A total of 120 pairs of 18F-FDG and 18F-FAPI PET images of the same patient scanned separately at different time points were collected,and the dual-tracer PET image was generated through simulation.After the image registration of PET images of two tracers for ensuring spatial position matching,the registered PET images were forward-projected to generate sinogram data,and the sinogram data of two tracers were accumulated to obtain mixed sinogram data.Subsequently,the dual-tracer PET image was reconstructed using maximum likelihood expectation maximization and input into a 3D DSN based network for image separation,thereby obtaining PET images of two single tracers.Results Compared with 3D CNN method,the proposed method increased the structure similarity index measure(SSIM)of the separated 18F-FDG images to the real 18F-FDG images by 0.87%,increased the peak signal-to-noise ratio(PSNR)by 11.8%,and reduced the normalized root mean square error(NRMSE)by 52%.The SSIM of the separated 18F-FAPI images to the real 18F-FAPI images increased by 1.1%,PSNR increased by 17.0%,and NRMSE decreased by 51%.Conclusion The proposed method can be effectively applied to simultaneous PET imaging with dual PET tracers,reducing the number of scans and costs in time and money,and providing clinical doctors more accurate and abundant diagnostic information.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To investigate the possible mechanisms underlying the involvement of the gut microbiota metabolite trimethylamine oxide (TMAO) in the pathogenesis of chronic spontaneous urticaria (CSU) .Methods:From June 2023 to June 2024, 67 CSU patients were enrolled from the Dermatology and Cosmetic Center, the Third Affiliated Hospital of Chongqing Medical University, and 69 age-matched healthy controls were also collected at the same time. Serum TMAO levels in both groups were measured using enzyme-linked immunosorbent assay (ELISA) , and D-dimer levels were collected from the CSU patients. A degranulation model was established in rat basophilic leukemia RBL-2H3 cells using anti-DNP IgE/DNP-BSA (IgE/Ag group) ; these cells were additionally grouped to be treated with different concentrations of TMAO (IgE/Ag+10 μmol/L TMAO group, IgE/Ag + 50 μmol/L TMAO group, IgE/Ag + 100 μmol/L TMAO group) ; untreated RBL-2H3 cells served as a blank control group. To investigate the effect of the extracellular signal-regulated kinase (ERK) phosphorylation inhibitor U0126 on the action of TMAO, RBL-2H3 cells were divided into another 5 groups: blank group, IgE/Ag group, IgE/Ag + 1 μmol/L U0126 group, IgE/Ag + 100 μmol/L TMAO group, and IgE/Ag + 100 μmol/L TMAO + 1 μmol/L U0126 group. In vivo, a localized allergic reaction model was established in the ears of C57BL/6 mice using anti-DNP IgE/DNP-BSA (IgE/Ag group) , and additional groups included blank group, IgE group, IgE/Ag + solvent (DMSO) group, and IgE/Ag + 10 μg/μl TMAO group. ELISA was performed to detect levels of inflammatory mediators in cell culture supernatants and mouse serum. Toluidine blue staining was employed to observe mast cell degranulation in the cell experiment and mouse ear tissue samples, Evans blue staining to assess vascular permeability in mouse ear tissue samples, and Western blot analysis to detect the ERK phosphorylation levels. The t test was used for comparisons between two groups, and one-way analysis of variance for multiple comparisons. Results:Serum TMAO levels were significantly higher in the 67 CSU patients than in the 69 healthy controls ( t = 13.27, P < 0.001) . Among the 32 CSU patients with available data about D-dimer, serum TMAO levels were positively correlated with D-dimer levels ( r = 0.62, P < 0.001) . In RBL-2H3 cell experiments, degranulation rates were significantly higher in the IgE/Ag + 10, 50, and 100 μmol/L TMAO groups than in the IgE/Ag group; morphologically, RBL-2H3 cells treated with 10, 50, and 100 μmol/L TMAO became increasingly rounded; 50 and 100 μmol/L TMAO significantly promoted the production of β-hexosaminidase (β-Hex) , interleukin-6 (IL-6) , and tumor necrosis factor-α (TNF-α) (all P < 0.01) , and upregulated ERK phosphorylation levels ( P < 0.01) ; the levels of ERK phosphorylation, IL-6, TNF-α, and β-Hex were significantly lower in the IgE/Ag + U0126 group than in the IgE/Ag group, as well as lower in the IgE/Ag + TMAO + U0126 group than in the IgE/Ag + TMAO group (all P < 0.001) . In the mouse model of localized allergic reaction, the IgE/Ag + TMAO group showed increased vascular permeability, edema degree, and mast cell degranulation, as well as significantly elevated ERK phosphorylation levels and TNF-α expression in mouse ear tissues compared with the IgE/Ag + DMSO group (both P < 0.05) . Conclusion:Elevated serum TMAO may participate in the pathogenesis of CSU by upregulating ERK phosphorylation levels in mast cells and skin tissues, thereby promoting IgE/Ag-mediated degranulation of effector cells and production of inflammatory mediators.

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

Objective:To summarize the clinical characteristics of autoimmune glial fibrillary acidic protein astrocytopathy(GFAP-A),in order to improve the understanding of the disease among clinical physicians.Methods:A retrospective analysis was conducted on the clinical manifestations,imaging examination,laboratory examination of a patient with GFAP-A who was admitted to the First People's Hospital of Yunnan Province and diagnosed on May 11,2023.Results:A female patient with GFAP-A,aged 67 years,presented with meningoencephalomyelitis.The head MRI showed abnormalities,with extensive lesions in the bilateral basal ganglia,pons,and lateral paraventricular white matter areas,and enhancement of the lateral ventricular ependyma and pia mater.Long segment spinal cord abnormal signals were observed,and cerebrospinal fluid anti GFAP antibodies were positive.After hormone treatment,the prognosis was good,and there was no recurrence during follow-up.Conclusion:The main clinical manifestations of GFAP-A are acute or subacute onset meningitis and/or encephalitis,myelitis and meningitis.Detection of autoimmune antibodies in ce-rebrospinal fluid can provide a clear diagnosis,and timely treatment can improve prognosis.