A 42-year-old male with chest tightness and dyspnea was admitted to the hospital. Chest CT indicated diffuse interstitial lung infiltration. Despite receiving anti-infective therapy, glucocorticoid therapy, and immunosuppressive agents, the patient developed refractory hypoxaemia. Endotracheal intubation and invasive mechanical ventilation failed to improve oxygenation. Therefore the patient was diagnosed with rapidly progressive interstitial lung disease (RP-ILD) accompanied by type Ⅰ respiratory failure. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) was initiated, and oxygenation improved in this patient. The patient subsequently underwent bilateral lung transplantation with veno-arterio-venous (VAV) ECMO support. ECMO machine was withdrawn on day 1, and extubation was achieved on day 9 after surgery. Histopathology revealed fibrotic nonspecific interstitial pneumonia (NSIP) with hyaline membrane formation. The patient developed ICU-acquired myasthenia and received early rehabilitation, with gradual recovery of muscle strength. During follow-up, graft lung function remained stable. This case demonstrates that ECMO can serve as a bridge to lung transplantation in RP-ILD patients.

OBJECTIVE To evaluate the efficacy and safety of total glucosides of paeonia （TGP） in the treatment of systemic lupus erythematosus （SLE）. METHODS Randomized controlled trial （RCT） about TGP combined with western medicine versus western medicine alone for SLE treatment were retrieved from PubMed， Embase， Cochrane Library， Web of Science， CNKI， VIP， Wanfang Data， and CBM. The search period spanned from the inception of each database to June 1， 2025. After literature screening， data extraction， and quality assessment of the included studies， Meta-analysis was performed using RevMan 5.4 software. RESULTS Fifteen RCTs， involving 1 318 patients， were included. Meta-analysis results showed that compared with western medicine alone， TGP combined with western medicine significantly improved clinical efficacy [OR＝4.96， 95%CI（3.41， 7.23）， P＜0.000 01]， complement 3 [MD＝0.18， 95%CI （0.13， 0.23）， P＜0.000 01] and complement 4[MD＝0.08， 般021） 95%CI （0.04， 0.11）， P＜0.000 01]， and reduced the levels of immunoglobulin G （IgG） [MD＝－3.10， 95%CI （－3.59，－2.62）， P＜0.000 01]， IgA [MD＝－0.68， 95%CI （－0.78， －0.58）， P＜0.000 01]， IgM [MD＝－0.43， 95%CI （－0.53，－0.34）， P＜0.000 01]， systemic lupus erythematosus disease activity index （SLEDAI） [MD＝－1.59， 95%CI （－2.20， －0.99）， P＜0.000 01]， recurrence rate [OR＝0.23， 95%CI （0.13， 0.42）， P＜0.000 01] and the incidence of adverse drug reactions [OR＝ 0.54， 95%CI （0.36， 0.82）， P＝0.004]. CONCLUSIONS TGP therapy can improve clinical efficacy of SLE patients， promote the restoration of immunoglobulins and complements， reduce SLEDAI and recurrence rate and has good safety.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective:To evaluate the effectiveness of entrustable professional activities (EPAs) in the general practice internship of undergraduate clinical medicine students, identify issues that need improvement in the internship, and enhance medical students' competence.Methods:A total of 75 students in the five-year (English class) clinical medicine program enrolled in 2018 and 2019 who participated in general practice internship in Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2021 to October 2023 were selected as study subjects. The design of core EPAs was adopted to assess the correlation among different EPA dimensions and to analyze the qualified rates.Results:The evaluation of EPAs showed that EPA2 (practicing respect, understanding and teamwork) had the highest mean score of 9.33, and EPA10 (chronic disease management and management of key populations) had the lowest mean score of 8.08. A supervision level of 3a and above was used as the criterion for qualification. The supervision levels of the students' EPAs were mostly concentrated at levels 3a and 3b. The highest qualified rate was for EPA2 (practicing respect, understanding and teamwork) at 85.33%, followed by EPA1 (complying with the rules of the profession and demonstrating professionalism) at 80.00% and EPA8 (reviewing information and solving clinical problems) at 72.00%. The lowest qualified rate was for EPA10 (chronic disease management and management of key populations) at 33.33%, followed by EPA4 (analyzing and interpreting test results) at 57.33%.Conclusions:EPAs concretize competency evaluation, which can effectively reflect the "competency-oriented" training objectives encompassing multiple elements such as knowledge, skills, values, and attitudes, while maintaining professional specificity. Undergraduates demonstrated strengths in professionalism and academics, but showed deficiencies in community chronic disease management and management of key populations. These findings suggest the need to strengthen the training in health and social care to better align with the competencies required during standardized residency training.

Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2％)were free of T2DM,158(11.7％)already had T2DM at baseline,and 96(7.1％)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0％of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7％vs.20.9％vs.26.0％,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95％CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95％CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.

Objective To analyse the clinical efficacy and safety of acupuncture combined with intermittent catheterisation in treating postoperative urinary retention after radical surgery for cervical cancer,and provide reference for the clinical treatment of postoperative urinary retention.Methods A retrospective analysis was conducted based on the clinical data of patients who underwent radical hysterectomy for cervical cancer at Obstetrics and Gynecology Hospital,Fudan University,from Sept 2019 to Dec 2021 and subsequently developed urinary retention.The patients were treated with a combination of acupuncture and intermittent catheterization.We observed residual urine volume,duration of acupuncture treatment,and urinary tract infection status to evaluate the effectiveness and safety of the acupuncture combined with intermittent catheterization regimen.We examined the relationship between treatment duration and various factors such as age,pathological type,surgical-pathological staging,surgical method,pre-treatment catheter indwelling time,pre-treatment residual urine volume,presence or absence of postoperative radiotherapy and chemotherapy,pre-existing urinary tract infection,and whether ureteral stenting was performed,in order to analyze the factors affecting the treatment duration.Results A total of 156 patients were reviewed.After treatment,132 cases had a post-treatment residual urine volume<100 mL,7 cases had a volume of 100-200 mL,and 15 cases had a volume>200 mL.Two cases still had great difficulty in urination after treatment,resulting in an overall effectiveness rate of 89.1%.No significant adverse events occurred in the patients.The treatment duration ranged from 2 to 17 days,with an average treatment time of 6.2 days.The treatment duration was a correlated with the preoperative indwelling catheter duration,residual urine volume and postoperative radiotherapy.Conclusion Acupuncture combined with intermittent catheterisation in treating urinary retention after radical surgery for cervical cancer has good efficacy,short treatment time and no obvious adverse effects,and can be an option for treating postoperative urinary retention.

OBJECTIVE: To explore the clinical and genetic characteristics of two children diagnosed with two rare genetic diseases simultaneously. METHODS: Two children with comorbidity of two genetic diseases due to dual genetic mutations diagnosed at the Third Affiliated Hospital of Zhengzhou University respectively in May 2022 and March 2023 were selected as the study subjects. Clinical and genetic data of the two children were retrospectively analyzed. This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-062-01). RESULTS: Child 1 was a 2-year-and-4-month-old boy whose clinical manifestations included facial dysmorphism, developmental delay, short stature, microcephaly, cleft palate, cryptorchidism, hypospadias, recurrent infections and immunological abnormalities. Whole exome sequencing revealed that he had harbored a heterozygous c.6595delT (p.Y2199Ifs*65) variant of the KMT2D gene and a heterozygous c.1892G>A (p.R631Q) variant of the PIK3R1 gene. This has led to a dual genetic diagnosis of Kabuki syndrome and PI3Kδ-related immunodeficiency type 36. Child 2 was a 15-year-old girl whose clinical manifestations included epilepsy, Albright's hereditary osteodystrophy, long body trunk, short limbs, hypocalcemia, hyperphosphatemia and hyperparathyroidism. The child also had a family history of short stature. Whole exome sequencing revealed that she had harbored a heterozygous c.2T>C (p.Met1?) variant of the GNAS gene and deletion of exons 2 to 6 of the SHOX gene. The two variants have led to dual diagnose of pseudohypoparathyroidism and X-linked idiopathic short stature. CONCLUSION When the clinical phenotype of a genetic disease is complex and cannot be fully explained with a single genetic variant, multiple pathogenic variants should be considered, and this may lead to the diagnosis of co-morbid genetic diseases. To adopt or supplement corresponding genetic testing in time and re-analyze the genetic data may facilitate accurate diagnosis of co-morbid genetic diseases.
Child, Preschool ; Female ; Humans ; Male ; Class Ia Phosphatidylinositol 3-Kinase/genetics* ; Comorbidity ; Exome Sequencing ; Mutation ; Rare Diseases/genetics* ; Retrospective Studies ; Adolescent

AIM To investigate the clinical effects of Mahuang Fuzi Xixin Decoction combined with non-immunosuppressive treatment on patients with focal segmental glomerulosclerosis due to Spleen-Kidney Yang Deficiency.METHODS Sixty patients were randomly assigned into control group(30 cases)for 24-week intervention of non-immunosuppressive treatment,and observation group(30 cases)for 24-week intervention of both Mahuang Fuzi Xixin Decoction and non-immunosuppressive treatment.The changes in clinical effects,TCM syndrome effects,TCM syndrome score,24 h UTP,ALB,eGFR,Nephrin,Podocin and safety indices were detected.RESULTS The observation group demonstrated higher total effective rate and TCM syndrome effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome score,24 h UTP,Nephrin,Podocin(P＜0.05),and increased ALB(P＜0.05),especially for the observation group(P＜0.05).No obvious adverse reactions occured in the two groups.CONCLUSION For the patients with focal segmental glomerulosclerosis due to Spleen-Kidney Yang Deficiency,Mahuang Fuzi Xixin Decoction combined with non-immunosuppressive treatment can improve TCM syndromes,whose action mechanism may be contribute to the alleviation of podocyte injury.

The amino-terminal pro-C-type natriuretic peptide(NT-proCNP)is a diagnostic inflam-matory marker clinically used for diagnosing bacterial infections.This study aims to establish a phage display library of single-chain variable fragment(scFv)antibodies against canine NT-proC-NP and to screen for scFvs with high binding affinity to NT-proCNP.Initially,NT-proCNP was prepared using prokaryotic expression system and was used to immunize New Zealand White rab-bits.Upon achieving the desired serum titer,total RNA was extracted from the splenocytes of rab-bits and reverse transcribed into cDNA.Using this cDNA as a template,degenerate primers were employed to amplify the genes of the rabbit antibody light chain variable region(VL)and heavy chain variable region(VH).The VL and VH regions were spliced together to form a complete scFv fragment via overlap extension PCR.The scFv was then ligated into the phagemid pComb3XSS and electroporated into competent E.coli TG1 cells to construct a rabbit-derived anti-NT-proCNP scFv immunological library.This library underwent four rounds of enrichment and screening to isolate specific single-chain antibodies.The selected antibody was subsequently ex-pressed in a soluble form within a prokaryotic system,and its immunological activity was evalua-ted.Using phage display technology,this study successfully identified a single-chain antibody scFv-1-CNP with strong antigen-binding activity and genetic sequence characteristics of scFvs,providing a research direction for further exploration of scFv applications in the detection of NT-proCNP.

Sepsis is a life-threatening organ dysfunction disease caused by a dysregulated host response to infection.It has com-plex pathophysiological changes,and in severe cases,it can rap-idly develop into septic shock and multiple organ dysfunction or multiple organ failure.At present,the pathological mechanism of sepsis and its induced organ dysfunction is complex and the in-fluencing factors are numerous.So far,there is still a lack of specific and effective treatment strategies.RNA modify-N6-methyladenosine(m6 A)is one of the most common post-tran-scriptional modifications on eukaryotic RNAs.It is involved in the regulation of the occurrence and development of a variety of inflammatory diseases,including sepsis,and even multiple organ dysfunction induced by sepsis by affecting the metabolism of RNAs.It includes cardiac dysfunction,acute lung injury(ALI)and acute kidney injury(AKI).Therefore,this article will dis-cuss the effect of m6A modification on the function of immune cells,and its important role in sepsis and its induced multiple or-gan dysfunction diseases by regulating inflammatory signals,py-roptosis,mitochondrial damage and ferroptosis.This will provide new therapeutic targets and strategies for the clinical prevention and treatment of sepsis and its induced multiple organ dysfunc-tion diseases.