Objective:To explore the application effect of the milestone evaluation system based on ACGME core competencies in the standardized training of residents in the department of rheumatology and immunology.Methods:A modified Milestone Evaluation Scale was developed for the department of rheumatology and immunology. Self evaluation and mentor evaluation were conducted on 150 residents who received standardized training in grades 1-3 before May 2023. The results were collected and statistically analyzed. One-way analysis of variance and t-test were performed using SPSS 27.0. Results:The self-evaluation and mentor evaluation scores of all residents increased with the training years. Self-evaluation scores were significantly higher than mentor evaluation scores ( P<0.05) for the medical knowledge ( t=2.95, P=0.006), diagnosis and treatment ability ( t=2.57, P=0.015), and learning ability ( t=2.67, P=0.015) of grade 2 residents and the learning ability ( t=2.87, P=0.007) of grade 3 residents. There were no significant differences in the baseline score and ability improvement of residents from different institutions ( P>0.05). Conclusions:The milestone evaluation system is an effective tool for training, assessing, and providing feedback to residents in rheumatology and immunology, and provides essential feedback to resident training bases regarding the training effectiveness. The method is worth promoting.

Objective To investigate the clinical characteristics of 16 patients with connective tissue diseases associated interstitial lung disease(CTD-ILD)complicated with lung cancer,and to improve the cognition of the disease.Methods Clinical data of 16 patients diagnosed as CTD-ILD associated with lung cancer,who were admitted to our center,were retrospectively analyzed,including general conditions,clinical characteristics,auxiliary examinations,pathological classification of lung cancer,TNM type,treatment and clinical outcome.Results Among the 16 CTD-ILD patients with lung cancer,there were 12 males and 4 females.The mean age at diagnosis of CTD-ILD was(64.7±9.2)years,and the mean age at diagnosis of lung cancer was(66.6±8.7)years.Lung occupying space on imaging(62.5%)was the most common initial symptom in lung cancer patients,followed by cough and phlegm(12.5%)and chest pain(12.5%).Of patients with lung cancer,adenocarcinoma(8 cases,50.0%)was the most common pathological type,followed by small cell lung cancer(4 cases,25.0%).The diagnosis time of CTD-ILD was earlier than that of lung cancer in 8 cases(50.0%),with a median time of 36.0(11.3,57.0)months,followed by 7 cases(43.8%)of CTD-ILD diagnosed with lung cancer at the same time.The diagnosis time of lung cancer was earlier than that of CTD-ILD in 1 case(6.3%).The most common TNM stage for lung cancer was stage Ⅳ(9 cases,56.25%).Sixteen patients were followed up from 1 to 64 months,with a median of 8.5(1.5,14.3)months.Eleven patients(68.8%)died,including 8 patients(72.7%)died of infection and 3 patients(27.3%)died of end-stage lung cancer.Conclusion For CTD-ILD patients,close follow-up and regular imaging monitoring are necessary to help early detection of lung cancer and improve prognosis.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Objective To investigate the prevalence and risk factors of injury among both primary and middle school students in Changning District， Shanghai， and to provide evidence for injury prevention. Methods In 2018， data of basic characteristics and injury-related factors were obtained through field questionnaire survey among the selected primary and middle schools （2 of each）. Results The study finally included 1 821 students， with injury incidence rate of 30.1%. Among them， the injury incidence rate for the primary schools was 32.0%， and 28.8% for the middle schools. The top three injury types were falls， sharps injuries， and blunt injuries. Age， gender， myopia， and injury-related knowledge/behaviors were significantly related to injury incidence. Conclusion Falls should still be the priority of injury prevention for primary/middle school students in Changning District. The effect of reducing injuries can be achieved by improving health education about injury-related knowledge/behaviors.

Hemophilia B is a genetic disorder caused by coagulation factor Ⅸ(FⅨ) deficiency, mainly manifesting as joint, muscle and deep tissue bleeding. Hemophilia pseudotumor is a mass formed by soft tissue liquefaction and necrosis caused by repeated bleeding. Most pseudotumors occur in the bone and muscle. We report a case of hemophilia B with pseudotumor formation in the pelvis and abdomen, where lesion location is relatively rare. After active and effective hemostasis, the patient's hematuria symptom gradually improved. This case suggests that early and timely hemostatic treatment is crucial for patients with hemophilia.

Objective:To analyze the clinical phenotype and molecular pathogenesis of nine patients with hereditary factor Ⅴ (FⅤ) deficiency.Methods:Nine patients with hereditary FⅤ deficiency who were admitted to the Institute of Hematology and Blood Diseases Hospital from April 1999 to September 2019 were analyzed. The activated partial thromboplastin time, prothrombin time, and FⅤ procoagulant activity (FⅤ∶C) were measured for phenotypic diagnosis. High-throughput sequencing was employed for the F5 gene mutation screening, Sanger sequencing was adopted to confirm candidate variants and parental carrying status, Swiss-model was used for three-dimensional structure analysis, and ClustalX v.2.1 was used for homologous analysis.Results:The FⅤ∶C of the nine patients ranged from 0.1 to 10.6. Among them, eight had a hemorrhage history, with kin/mucosal bleeding as the most common symptom (three cases, 37.5%) , whereas one case had no bleeding symptom. There were five homozygotes and four compound heterozygotes. A total of 12 pathogenic or likely pathogenic mutations were detected, of which c.6100C>A/p.Pro2034Thr, c.6575T>C/p.Phe2192Ser, c.1600_1601delinsTG/p. Gln534*, c.4713C>A/p.Tyr1571*, and c.952+5G>C were reported for the first time.Conclusion:The newly discovered gene mutations enriched the F5 gene mutation spectrum associated with hereditary FⅤ deficiency. High-throughput sequencing could be an effective method to detect F5 gene mutations.

OBJECTIVE：To study the effects of Calpeptin inhibitor Calpeptin on the transformation and stemness markers expression induced by estradiol（E2），and to investigate its mechanism. METHODS ：Taking human mammary epithelial cells MCF-10A as research object ，transformed cells were induced by E 2 treatment. Cells were divided into control group （0.1％DMSO）， E2-transformed group （50 nmol/L），E2-transformed+Calpeptin group （50 nmol/L E 2+1 μmol/L Calpeptin），then continuously treated with corresponding drug-containing culture medium for 15 generations. Then ，MTT assay was used to determine the proliferation rate of cells （24，48 h）；plate colony test was used to detect the Clone formation rate of cells ；the number of sphere-forming cells was measured by suspension spheroidization test ；mRNA expressions of stemness marker （CD44，Nanog，OCT4）and extracellular sigal-regulated kinase （ERK）were detected by RT-qPCR ，and protein expressions of CD 44，Nanog，OCT4 ，ERK and p-ERK were detected by Western blotting assay. Another E 2-transformed cells were divided into control group （0.1％DMSO）and U0126 （ERK inhibitor ）group（10 μmol/L）. Clone formation rate ，the number of sphere-forming ，protein expressions of CD 44，Nanog， OCT4，ERK and p-ERK were determined with above methods ，and to validate the relationship of ERK inhibition with transformed cell behavior and the expression of stemness markers. RESULTS ：Compared with control group ，proliferation rate and clone formation rate of E 2 transformed group were increased significantly （P＜0.01），and the number of sphere-forming was increased significantly（P＜0.01）；mRNA expression levels of CD 44，Nanog，OCT4，ERK and protein expression levels of CD 44，Nanog， OCT4 and p-ERK in cells were increased significantly （P＜0.01）. Compared with E 2-transformed group ，proliferation rate （24，48 h）and clone formation rate of E 2-transformed + Calpeptin group were decreased significantly （P＜0.01），and the number of sphere-forming was decreased significantly （P＜0.05）；mRNA expression levels of CD 44，Nanog，OCT4 ，ERK and protein expression levels of CD 44，Nanog，OCT4，p-ERK in cells were decreased significantly （P＜0.05 or P＜0.01）. After treated with ERK inhibitor U 0126，clone formation rate of E 2-transformed cells ，the number of sphere-forming ，protein expression levels of CD44，Nanog，OCT4 and p-ERK were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：Calpeptin can inhibit the transformation and the expression of stemness markers of human mammary epithelial cells MCF- 10A，and the mechanism of it may be associated with inhibiting the activation of Calpain-ERK signaling pathway.

Objective: To explore the current situation of college students’ delivery food consumption and the related factors, and to provide reference for healthy eating behaviors among college students. Methods: A random cluster sampling was used to select 2 597 student sample of various majors and grades of Wuhan University of Science and Technology. The self-made questionnaire was used to investigate the frequency and causes of college students ordering delivery food, as well as the status of nutrition knowledge, attitude and behavior. The Zung Depression Self-rating Scale (SDS) was adopted to measure the mental health status of the students, and height and weight were measured by a unified height and weight scale. Finally, the influencing factors mentioned above and consumption frequency of delivery food was analyzed. Results: Among the college students,60.0% reported the habit of ordering delivery food; As for the frequency of delivery food consumption, boys were singnificantly higher than girls(OR=1.38), students of first(OR=0.48) and third grade(OR=0.61) were lower than that of fourth grade,the medicine major’s frequency was lower than the science and engineering major’s(OR=0.57), and the art major’s was higher than the science and engineering’s(OR=1.94); The frequency of students who had received relevant health education was lower than the unreceived students’(OR=0.70); Students who had better performance in the nutrition learning attitude, and those who had healthier eatting habits (OR=0.62, 0.49); Students who saving reckoned delivery food as convenient, time and tasty (OR=4.77, 4.82, 2.85); Howver, students’ BMI, the score of depression scale, nutritional knowledge score, knowledge and practical attitude,diet structure score, food packaging, price and nutritional factors showed no significant effect on the frequency of delivery food consumption (P>0.05). Conclusion It is common for college students to order delivery food. gender, grade, major, nutrition and health education background, nutritional attitude, eating habits and convenient, time-saving, tasty nature of fast food are the factors influencing the frequency of delivery food consumption.

Objective:To explore the effect of previous intestinal resection on anastomotic fistula within 30 days after surgery in Crohn′s disease.Methods:The clinical data from 92 Crohn′s disease patients who underwent intestinal resection and anastomosis at the Department of General Surgery in Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine from Jan 2016 to Sep 2019. Patients were divided into no previous intestinal resection group ( n=45) and previous intestinal resection group ( n=47). The relationship between previous intestinal resection and postoperative anastomotic leak in Crohn′s disease patients with intestinal resection and anastomosis was analyzed. Results:A total of 11 cases (12% leak rate) underwent postoperative anastomotic leak. There were 2 leaks in patients with no previous history of intestinal resection, while 9 leaks in patients with previous bowel resection (χ 2 =4.722, P=0.03). The OR of the postoperative anastomotic leak in Crohn′s disease patients with previous intestinal resection compared with no previous intestinal resection group was 5.092 (95% CI: 1.035-25.048). Patients with 1 previous resection (24 cases) had a leak rate of 13%, whereas patients with >1 previous resection episodes (23 cases) had a leak rate of 26%. The number of previous resection episodes correlated with an increasing risk for clinical anastomotic leak (correlation coefficien r=0.995). Conclusions:Previous intestinal resection is an independent risk factor for ensuing postoperative anastomotic leak in Crohn′s disease patients with intestinal resection and anastomosis.

Background/Aims: Lipopolysaccharide (LPS) is the key factor inducing mucosal and systemic inflammation in various intestinal and parenteral diseases, which could initially disrupt the epithelial barrier function. EphrinA1/ephA2 is speculated to increase the epithelial permeability for its “repulsive interaction” between adjacent cells. This study aim to investigate the role of ephrinA1/ephA2 in LPS-induced epithelial hyperpermeability. Methods: In vivo model challenged with oral LPS in C57BL/6 mice and in vitro model exposed to LPS in Caco2 monolayer were established. The barrier function was assessed including expression of tight junction proteins (occludin and claudin-1), transepithelial electrical resistance, and permeability to macromolecules (fluorescein isothiocyanate-labeled fluorescent dextran 4 kDa [FD4]). Moreover, the expression and phosphorylation of ephrinA1/ephA2 were quantified, and its roles in the process of epithelial barrier disruption were confirmed via stimulating ephA2 with ephrinA1-Fc chimera (ephrinA1-Fc) and inactivating ephA2 with ephA2-Fc chimera (ephA2-Fc), or ephA2 monoclonal antibody (ephA2-mab), as well as inhibiting extracellular signal-regulated kinase 1/2 (ERK1/2) with PD98059. Results: LPS induced significant barrier dysfunction with dismissed occludin and claudin-1 expression, reduced transepithelial electrical resistance and increased FD4 permeability, accompanied by upregulated ephrinA1/ephA2 pathway and phosphorylation of ephA2 receptor. Furthermore, ephA2-Fc, and ephA2-mab ameliorated LPS-induced epithelial hyperpermeability, which was also inhibited by PD98059. Additionally, ephrinA1-Fc led to apparent epithelial leakage in Caco2 monolayer by promoting the phosphorylation of ERK1/2, which could be obviously blocked by ephA2-mab and PD98059. Conclusion EphrinA1/ephA2 promotes epithelial hyperpermeability with an ERK1/2-dependent pathway, which involves in LPS-induced intestinal barrier dysfunction.