BACKGROUND:Hypoxia is strongly associated with the development and progression of osteoarthritic chondrocyte injury,but the specific targets and regulatory mechanisms are unclear. OBJECTIVE:A machine learning approach was used to identify KDEL(Lys-Asp-Glu-Leu)receptor 3(KDELR3)as a characteristic gene for osteoarthritis hypoxia and immune infiltration analysis,to provide new ideas and methods for the treatment of osteoarthritis. METHODS:The osteoarthritis-related datasets were downloaded from the GEO database and the GSEA website to obtain hypoxia-related genes.The osteoarthritis datasets were batch-corrected and immune infiltration analyzed using R language,and osteoarthritis hypoxia genes were extracted for differential analysis.Differentially expressed genes were analyzed for GO function and KEGG signaling pathway.Weighted correlation network analysis(WGCNA)and machine learning were also used to screen osteoarthritis hypoxia signature genes,and in vitro cellular experiments were performed to validate expression and correlate immune infiltration analysis using the datasets and qPCR. RESULTS AND CONCLUSION:(1)8492 osteoarthritis genes were obtained by batch correction and principal component analysis,mainly strongly associated with immune cells such as Macrophages M2 and Mast cells resting;200 hypoxia genes were also obtained,resulting in 41 osteoarthritis hypoxia differentially expressed genes.(2)GO analysis involved mainly biological processes such as response to nutrient levels and glucocorticoids;cellular components such as lysosomal lumen and Golgi lumen;and molecular functions such as 14-3-3 protein binding and DNA-binding transcriptional activator activity.(3)KEGG analysis of osteoarthritis hypoxia differentially expressed genes was associated with signaling pathways such as PI3K-Akt,FoxO,and microRNAs in cancer.(4)The characteristic gene KDELR3 was obtained after using WGCNA analysis and machine learning screening.(5)The gene expression of KDELR3 was found to be higher in the test group than in the control group in the synovium(P=0.014)but lower in the meniscus(P=0.024)after validation by gene microarray.(6)In vitro chondrocyte assay showed that the expression of KDELR3 was higher in cartilage than in the control group(P=0.005),while KDELR3 was closely associated with Macrophages M0(P=0.014)and T cells follicular helper(P=0.014).Using a machine learning approach,we confirmed that KDELR3 can be used as a hypoxic signature gene for osteoarthritis and may intervene in osteoarthritis pathogenesis by improving hypoxia,expecting to provide a new direction for better treatment of osteoarthritis.

BACKGROUND:Ferroptosis is strongly associated with the occurrence and progression of osteoarthritis,but the specific characteristic genes and regulatory mechanisms are not known. OBJECTIVE:To identify osteoarthritis ferroptosis signature genes and immune infiltration analysis using the WGCNA and various machine learning methods. METHODS:The osteoarthritis dataset was downloaded from the GEO database and ferroptosis-related genes were obtained from the FerrDb website.R language was used to batch correct the osteoarthritis dataset,extract osteoarthritis ferroptosis genes and perform differential analysis,analyze differentially expressed genes for GO function and KEGG signaling pathway.WGCNA analysis and machine learning(random forest,LASSO regression,and SVM-RFE analysis)were also used to screen osteoarthritis ferroptosis signature genes.The in vitro cell experiments were performed to divide chondrocytes into normal and osteoarthritis model groups.The dataset and qPCR were used to verify expression and correlate immune infiltration analysis. RESULTS AND CONCLUSION:(1)12 548 osteoarthritis genes were obtained by batch correction and PCA analysis,while 484 ferroptosis genes were obtained,resulting in 24 differentially expressed genes of osteoarthritis ferroptosis.(2)GO analysis mainly involved biological processes such as response to oxidative stress and response to organophosphorus,cellular components such as apical and apical plasma membranes,and molecular functions such as heme binding and tetrapyrrole binding.(3)KEGG analysis exhibited that differentially expressed genes of osteoarthritis ferroptosis were related to signaling pathways such as the interleukin 17 signaling pathway and tumor necrosis factor signaling pathway.(4)After using WGCNA analysis and machine learning screening,we obtained the characteristic gene KLF2.After validation by gene microarray,we found that the gene expression of KLF2 was higher in the test group than in the control group in the meniscus(P=0.000 14).(5)In vitro chondrocyte assay showed that type Ⅱ collagen and KLF2 expression was lower in the osteoarthritis group than in the control group in chondrocytes(P<0.05),while in osteoarthritis ferroptosis,mast cells activated was closely correlated with dendritic cells(r=0.99);KLF2 was closely correlated with natural killer cells(r=-1,P=0.017)and T cells follicular helper(r=-1,P=0.017).(6)The findings indicate that using WGCNA analysis and machine learning methods confirmed that KLF2 can be a characteristic gene for osteoarthritis ferroptosis and may improve osteoarthritis ferroptosis by interfering with KLF2.

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

The global pandemic of coronavirus disease 2019 (COVID-19) has brought great challenges to the traditional medical model. During the outbreak of COVID-19 in Shanghai, China, from March to May, 2022, there was a significant increase in the number of pediatric cases due to high transmissibility, immune escape, and vaccine breakthrough capacity of Omicron variants. The designated hospitals for children with COVID-19 served as a connecting link between children's specialized hospitals and mobile cabin hospitals. From April 7 to June 2, 2022, a total of 871 children with COVID-19 were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine (South Branch), a designated hospital for children with COVID-19. Among these patients, 568 (65.2%) were children under 3 years old, 870 (99.9%) were mild or moderate, and 1 was severe. This article reports the experience in the management of pediatric cases in this designated hospital, which included the following aspects: establishing an optimal case-admission process; strengthening multidisciplinary standardized diagnosis and treatment; optimizing the management, warning, and rescue system for severe COVID-19; implementing family-centered nursing care; formulating an individualized traditional Chinese medicine treatment regimen; optimizing the discharge process and strengthening bed turnover; implementing strict whole-process control to reduce the risk of nosocomial infection; constructing a structured medical record system and using information platforms to adapt to the work mode of large-volume cases; conducting scientific research and sharing the experience in diagnosis and treatment.
COVID-19 ; Child ; Child, Preschool ; China ; Hospitals, Pediatric ; Humans ; SARS-CoV-2

In order to build a unified teaching pattern integrating knowledge delivery, skill cultivation and value guidance, this article, based on the targets of cultivating medical talents in the new era, aims to explore the pathway of curriculum ideological and political education in Medical Parasitology teaching based on the situation of Yunnan Province. By analyzing the epidemiology of parasitic diseases in Yunnan Province, the remarkable achievements of parasitic diseases control in China and Yunnan Province, cases with parasitic disease misdiagnosis, parasitologists ’ selfless contributions, the contributions of traditional Chinese medicines to parasitic diseases control and the contributions of traditional Chinese medicines in Yunnan Province, the ideological and political education is naturally integrated into Medical Parasitology teaching, to create an educational model combining professional course teaching with ideological and political education curriculum.

The globalized epidemic of the COVID-19 forced the international community to reconsider the importance and urgency of global public health in world peace and development. The authors analyzed the COVID-19 epidemic prevention and control situation in Africa, and discussed the functions and layout of China-Africa friendship hospitals from the perspective of global health governance. It was suggested that the functions of China-Africa friendship hospitals should be positioned as the high-level medical centers in Africa, regional medical and disease control linkage centers, regional health technology training centers, regional telemedicine collaboration center, and regional health policy research center.Furthermore, the layout of China-Africa friendship hospitals should respond to China′s assistance in the construction of Africa′s center for disease control and China-Africa′s cooperation plan for promoting the " one belt and one road" construction, and work together with the medical team to build a new pattern of medical integration and health care system for African disease prevention and control and medical treatment.

OBJECTIVE：To systematically e valuate the effectiveness of inhaled corticosteroids combined with tiotropium bromide versus inhaled corticosteroids alone in the treatment of asthmatic-COPD overlap syndrome ，and to provide evidence-based reference for clinical use. METHODS ：Retrieved from PubMed ，Web of Science ，Embase，Cochrane Library ，CBM，CNKI， VIP，Wanfang database ，during the establishment of the database to Nov. 2019，randomized controlled trials （RCT）about inhaled corticosteroids combined with tiotropium bromide （trial group ）versus inhaled corticosteroids alone （control group ）in the treatment of asthmatic-COPD overlap syndrome were collected. After data extraction of included literatures met inclusion criteria ，quality evaluation with modified Jadad scale ，Meta-analysis was performed for response rate ，forced expiratory volume in the first second （FEV1），forced vital capacity （FVC），FEV1/FVC，inspiratory fraction （IC/TLC），residual to total ratio （RV/TLC），asthma symptom（ACT）score，chronic obstructive pulmonary symptom （CAT）score，the times of acute exacerbations by Rev Man 5.3.0 software. RESULTS ：A total of 25 RCTs were included ，involving 2 828 patients. The results of Meta-analysis showed that the response rate [RR ＝1.16，95％CI（1.10，1.22），P＜0.001]，FEV1[MD＝0.44，95％CI（0.35，0.54），P＜0.001]，FVC [MD ＝0.70， 95％CI（0.46，0.95），P＜0.001]，FEV1/FVC [MD= 8.79，95％CI（6.22，11.37），P＜0.001]，IC/TLC [MD ＝4.93，95％CI（3.01， 6.85），P＜0.001]，RV/TLC [MD ＝－9.22，95％CI（－9.79，－8.66），P＜0.001]，ACT score [MD ＝5.38，95％CI（4.30，6.47）， P＜0.001]，CAT score [MD ＝－3.67，95％CI（－4.89，－2.45），P＜0.001] and the times of acute exacerbations [MD ＝－1.49， 95％CI（－2.82，－0.17），P＝0.03] in trial group were significantly higher than control group ，with statistical significance. CONCLUSIONS：Compared with inhaled corticosteroids alone ，inhaled hormone combined with tiotropium bromide can improve the response rate and pulmonary function ，but increase the times of acute exacerbation of patients with asthmatic-COPD overlap syndrome.

Objective To discuss the feasibility and the curative effect of transurethral diverticulum section in the treatment of female urethral diverticulum.Method We retrospectively analyzed the transurethral diverticulum section surgeries of 11 adult female patients diagnosed as urethral diverticulum in our hospital from August 2012 to October 2016.The patients aged from 33 years old to 74 years old with an average age of 43.Their medical histories varied from 1 month to more than 40 years with an average histories of 80 months.Major symptoms included odynuria,frequent micturition,dyspareunia,perineum bearing-down feeling,repetitive urinary tract infection,dysuria,urinary stuttering,penis masses,etc.One patient underwent TVT-O.Two patients had urinary catheterization before the disease.During physical examination,cystic masses of different sizes could be touched on anterior vaginal walls with pain and secretion.Cystic lesions can be found by imaging examination.Transurethral diverticulum section was performed under general anesthesia.Using needle electrode by resectoscope,we made an annular incision in the direction of the vertical axis of the urethra,from the beginning of diverticulum ostium.The diverticulum completely communicated with the urethra.In 11 patients of transurethral endoscopic,the urethral sphincter and the diverticulum wall appeared morphological integrity and no damage.There was no liquid drained to de vagina.There was no urethral sphincter injury and no urethral vaginal leakage.We observed the operation time,bleeding volume,diverticulum position,the number of diverticulum,urethral sphincter intraoperative.We also observed the postoperative symptoms,short-term and long-term complications.Result All surgeries went on well,in which urethral diverticula were fully opened.The operation time was 30-45 minutes,average 35 minutes.The amount of bleeding within 5 ml.4 cases with multiple diverticulum,with 2 cases of diverticulum ostia were 2,2 cases of diverticulum ostia were 3.The other 7 cases with single diverticulum,diverticulum ostium was 1.The catheters were removed 2 weeks after the surgery,after that all patients can urinate normally.The follow-up time was 5-55 months (mean,24 months).All pre-surgical symptoms disappeared and no complication occurred,such as urethral stricture,urinary incontinence,urethro-vaginal fistula,etc.Conclusion Transurethral diverticulum section is a reliable treatment for female urethral diverticulum with positive curative effect and no obvious complication.

Objective:To describe the surgical technique of direct anterior approach to total hip arthroplasty and to report the early clinical outcomes.Methods: A series of 100 consecutive,unselected patients who had 116 primary total hip arthroplasty surgeries (16 bilateral) done through direct anterior approach from March 11 2015 to June 21 2016 was reviewed.There were 50 male patients and 50 female patients.The average patient age was 51 years,and the average body mass index was 24.69 kg/m2.The preoperative diagnosis included avascular necrosis of femoral head,hip osteoarthritis,osteoarthritis se-condary to acetabular dysplasia,sequelae of hip old infection,ankylosing spondylitis,rheumatoid arthritis and avascular necrosis of femoral head after cannulated screws fixation of femoral neck fracture.There were 7 hips which had surgical history prior to the index hip arthroplasty,including 3 cases with bone graft treatment for avascular necrosis of femoral head through Smith-Peterson approach,2 cases with acetabular shelf procedures for acetabular dysplasia through Smith-Peterson approach,and 2 cases with cannulated screws fixation for femoral neck fracture (internal fixation residual).All were uncemented hips.The stems used in this study included 67 Triloc stems (DePuy company,USA),45 Corail stems (DePuy company,USA),2 Accolade stems (Stryker company,USA),1 Synergy stem (Smith-Nephew company,USA) and 1 Polarstem (Smith-Nephew company,USA).Results: The average follow up period was 8.5 months,the average incision scar length was 10 cm,and the average postoperative Harris score was 93.62.There was 95％ postoperative leg length discrepancy within 3 mm.The average cup inclination angle was 38.7°with 94.8％ in the range of 30° to 50°.The average cup anteversion angle was 14.3° with 94.2％ within the target range of 5° to 25°.The were 15 (12.9％) operative complications,including two femoral perforations (changing stem from Triloc to Corail),three calcar fractures (treated with cerclage wires),four greater trochanter fractures (2 were treated wire tension band,and 2 nondisplaced fractures untreated),one deep infection (debridement and retaining of the prothesis),one superficial infection (debridement),one hematoma and three wound healing complications (debridement).All the complications were successfully treated without any sequelae at the end of the latest follow-up.There was no postoperative dislocation.There was no major nerve and vascular injuries.There were 35 cases (30.2％) reporting symptoms of lateral femoral cutaneous nerve palsy.Conclusion: Direct anterior approach to total hip arthroplasty allows accurate and reproducible cup orientation positioning and leg length restoration and decreases the risk of postoperative dislocation,which is helpful for early rapid postoperative recovery.