Objective:To investigate the effect of rapamycin on the proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts (RA-FLS) and its mechanism.Methods:Synovial tissues were collected from patients with RA during joint replacement surgery, and primary synovial fibroblasts were extracted by trypsin digestion. The effect of rapamycin on the proliferation of RA-FLS was detected by cell counting kit (CCK-8) method. RA-FLS were divided into the control group and the rapamycin group (10 nmol/L). The effect of rapamycin on apoptosis of RA-FLS cells was detected by flow cytometry. The mRNA expres-sion levels of mammalian target of rapamycin (mTOR), serine/threonine-protein kinase AKT, B lymphocy-toma-2 (Bcl-2) associated X gene (Bax) and Bcl-2 were detected by RT-PCR. The protein expression levels of Bax, Bcl-2, mTOR, p-mTOR (2448), AKT, p-AKT and mTORC1 downstream related molecules protein S6 kinase 1(S6K1), p-S6K1, eukaryotic translation initiation factor-binding protein 1 (4EBP1) and p-4EBP1 were detected by Western blot. Differences between the two groups were compared using two independent samples t-test. Results:The results showed that the proliferation efficiency of RA-FLS treated with rapamycin was significantly weaker than that of the control group, and the drug inhibition rate of rapamycin increased with the increase of rapamycin concentration. The apoptosis rate of rapamycin group was significantly higher than that of the control group (5.31±0.59)% vs (3.49±0.40)%, t=7.83, P=0.001). The expression of Bax mRNA in rapamycin group was significantly increased (1.35±0.04 vs 1.00±0.00, t=15.60, P=0.004), while the expression of Bcl-2 mRNA (0.790±0.003 vs 1.000±0.000, t=85.50, P=0.007), mTOR mRNA (0.41±0.08 vs 1.00±0.00, t=14.37, P=0.044) and AKT mRNA (0.59±0.08 vs 1.00±0.00, t=7.54, P=0.017) were decreased, and the differences were statistically significant when compared with the control group. Compared with the control group, the protein expression of Bax in rapamycin group was significantly increased (0.75±0.10 vs 0.48±0.09, t=4.04, P=0.007), and the expression levels of Bcl-2 (0.632±0.055 vs 0.758±0.020, t=7.35, P=0.002), p-AKT/AKT(0.61±0.07 vs 0.88±0.04, t=5.61, P=0.005), p-mTOR/mTOR(0.92±0.12 vs 1.28±0.09, t=5.05, P=0.002), p-S6K1/S6K1(0.884±0.020 vs 1.023±0.058, t=4.52, P=0.004) and p-4EBP1/4EBP1 were decreased(0.86±0.05 vs 1.11±0.05, t=6.00, P=0.004). Conclusion:Rapamycin may inhibit the proliferation and induce apoptosis of RA-FLS cells by inhibiting AKT/mTORC1 pathway.

Group A Streptococcus (GAS) is a very important pathogen, especially for children.On a global scale, GAS is an important cause of morbidity and mortality.But the burden of disease caused by GAS is still unknown in China and also has not obtained enough attention.For this purpose, the expert consensus is comprehensively described in diagnosis, treatment and prevention of GAS diseases in children, covering related aspects of pneumology, infectiology, immunology, microbiology, cardiology, nephrology, critical care medicine and preventive medicine.Accordingly, the consensus document was intended to improve management strategies of GAS disease in Chinese children.

Size of the macular hole (MH) is an important factor affecting the treatment of MH.MH with a diameter >400 mm was defined as large MH.Pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) peeling or intravitreal gas tamponade, which can effectively relieve the traction of vitreoretinal interface, is the standard surgical technique for idiopathic full-thickness macular hole (FTMH), but its efficacy on refractory large FTMH is very limited.In order to obtain ideal anatomical healing and functional recovery of large FTMH, new surgical strategies, such as reversal of retinal internal limiting membrane (ILM), expanded removal of ILM, transplantation of different tissue valves, application of mesenchymal stem cells and so on, have been the focus of researchers in the field of fundus diseases.More targeted and personalized treatment is the development trend of treatment for large FTMH.The progress of ILM flipping surgery, expansion of ILM removal, transplantation of different tissue valves, biomaterials and other auxiliary techniques in the treatment of large diameter FTMH were reviewed in this article.

Objective:To explore the link between the differentially expressed long non-coding RNAs (lncRNAs) and the number of regulatory T cells (Tregs) by detecting the lncRNAs expression profiles in patients with systemic lupus erythematosus (SLE), then analyze the correlation between Tregs and lncRNAs and the clinical features of SLE patients. We also predict the mechanism by which lncRNAs regulate the differentiation and development of Tregs, and provid new approach for the treatment of SLE.Methods:Peripheral blood of 9 active SLE patients was collected and mononuclear cells (PBMCs) were extracted. The lncRNAs expression profiles of PBMCs was analyzed by whole transcriptome sequencing. Nine healthy people served as controls to screen the differentially expressed lncRNAs, and to analyze the correlation between lncRNAs and Tregs number. Pearson test was used to analyze the correlation between lncRNA and the number of Tregs, and the correlation between Treg-associated lncRNAs and systemic lupus erythematosus disease activity index(SLEDAI) score, erythrocyte sedimentation rate (ESR), C3, C4 in SLE patients. The targeted genes of Treg asso-ciated lncRNAs were predicted with miRcode and Targetscan databases and co-expression network.Results:There were 240 differentially expressed lncRNAs in SLE patients compared with healthy controls, including 134 highly expressed lncRNAs ( P<0.05) and 106 low expressed lncRNAs ( P<0.05). The expression of ANKRD44-AS1 ( r=0.74, P=0.022), LINC00200 ( r=0.70, P=0.037), AP001363.2 ( r=0.78, P=0.014) and LINC02824 (r=0.79, P=0.011) were positively correlated with the number of Tregs, and the expression of AP000640.1 ( r=-0.72, P=0.028), AC124248.1 ( r=-0.77, P=0.016), LINC00482 ( r=-0.83, P=0.005) and MIR503HG ( r=-0.96, P<0.001) were negatively correlated with the number of Tregs. Among these eight Tregs associated lncRNAs, the expression of LINC00482 ( r=-0.73, P<0.001) and MIR503HG ( r=-0.76, P<0.001) were negatively correlated with C3. LINC00200, ANKRD44-AS1 and AP000640.1 related to Tregs regulated the expression of STAT5, PLD1, HOPX and RUNX3 through competitively binding of miRNA or transregulatory mechanism, thereby regulating the differentiation and development of Tregs. Conclusion:The lncRNAs expression profiles are changed in SLE patients, the differentially expressed lncRNAs are associated with abnormal number and function of Tregs in SLE patients, and Treg associated lncRNAs are associated with SLE disease activity, which may affect the expression of STAT5, PLD1, HOPX, RUNX3 and regulate Tregs function and participate in the pathogenesis and progression of SLE by competitively binding to miRNAs or trans-regulatory mechanism.

Patient satisfaction is one of the core indicators to measure the service quality of medical institutions. To this end, a multi-campus public hospital in Shanghai constructed a management system of patient satisfaction evaluation. Since 2021, its call center has conducted a full coverage satisfaction assessment for discharged patients from its three campuses and collected dissatisfaction information feedback. The hospital organized relevant clinical departments and functional departments to fully communicate with the dissatisfied patients according to the feedback information, followed by a joint rectification. The hospital regularly conducts in-depth analysis of all complaints for timely discovery of common problems in different campuses for continuous improvement. This practice can provide reference for multi-campus hospitals to promote homogeneous management, to improve management efficiency, service quality and patient satisfaction.

Objective:To understand clinical characteristics, treatment effects and prognosis of children with methylmalonic acidemia (MMA) presented with hemolytic uremic syndrome(HUS).Methods:The medical records of children with MMA were collected in Beijing Children′s Hospital, Capital Medical University from January 2012 to January 2019, the clinical manifestations, laboratory, imaging material, inspection results, renal pathological, gene analysis, treatment effect, and prognosis of MMA children with renal damage were analyzed, and were followed-up for 1-7 years.Results:Thirty cases were diagnosed as MMA with secondary renal damage.Eight cases(26.67%) showed as MMA-HUS.Age was from 1 month and 14 days to 12 years and 10 months old.There were 4 males and 4 females.The concentration of urine methylmalonic acid increased by 10-62 times.All were combined with hyperhomocysteine(HCY). The level of serum methylmalonic acid(1.5-11.8 mg/L), propylene carnitine(6.33-9.77 μmol/L)and the ratio of propylene /ethylene carnitine (0.24-0.29)were increased.Manifested as the mental and physical development retardation, anemia, jaundice, renal dysfunction, platelet reduction, hematuria, proteinuria in 8 cases, hypertension in 6 cases, frequent vomiting and convulsions in 2 cases.Two cases had a positive family history.Renal pathology showed that mesangial cells and mesangial matrix proliferation broadening, electron dense deposits no mesangial area, renal tubular epithelial cell swelling degeneration, immunofluorescence was negative.Two cases were genetically analyzed. One case was a CblC type MMACHC compound heterozygous mutation[c.80A>G(p.Q27R); c.217C>T(p.R73X)] and CblX type HCFC1 heterozygous mutation [c.3757G>A(p.R1253C)] double mutation; 1 case was a CblC type MMACHC compound heterozygous mutation[c.365A>T(p.H122L); c.609 G>A(p.W203X)]. Children diagnosed were treated with vitamin B 12, etc.Four cases of children gave up.The others, after treatment, were improved. Conclusions:MMA-HUS might be associated with multiple organ failure.Early diagnosis was the key, timely treatment could effectively control the disease, improve the prognosis.It should be followed up for ever.

Objective:To explore the clinical characteristics of chronic kidney disease (CKD) at the stage 3-5D in children with renal anemia, and provide reference data for standardized diagnosis and treatment.Methods:A single-center retrospective study was conducted to collect clinical data in children with CKD at Beijing Children's Hospital Affiliated to Capital Medical University from January 2016 to December 2018. The patients were divided into CKD stage 3 group, stage 4 group and stage 5 group according to estimated glomerular filtration rate. The indexes of anemia among the groups were compared. Data on anemia indicators, treatment, and anemia improvement in maintenance dialysis children at stage 5D were analyzed.Results:A total of 171 children with CKD were included in the study. The hemoglobin levels in CKD stage 3 group, stage 4 group and stage 5 group were (126.4±20.5) g/L, (90.8±26.0) g/L and (78.7±18.4) g/L, respectively, and there was a statistical difference among the groups ( χ2=61.982, P<0.001; trend test F=71.061, P<0.001). The incidences of anemia in children with CKD stage 3, stage 4 and stage 5 were 27.3% (9/33), 83.3% (25/30) and 95.4% (105/108), respectively. Mild, moderate and severe anemia in children with CKD stage 3 accounted for 15.2%(5/33), 12.1% (4/33) and 0(0), respectively. Mild, moderate and severe anemia in children with CKD stage 4 accounted for 26.7% (8/30), 50.0% (15/30) and 6.7% (2/30), respectively. Mild, moderate and severe anemia in children with CKD stage 5 accounted for 21.3%(23/108), 60.2%(65/108) and 15.8%(17/108), respectively. Anemia type was mostly normocytic anemia. The hemoglobin of 30 children with CKD stage 5D at the initial stage of dialysis was (79.3±16.3) g/L. Twenty-three children with CKD stage 5D received erythropoietin combined with oral iron or intravenous iron therapy. The hemoglobin compliance rates in children with maintenance dialysis in initial phase, 1 month, 2 months and 3 months were 6.7% (2/30), 16.7%(5/30), 63.3%(19/30) and 90.0%(27/30), respectively. The correction time for anemia was (2.5±1.0) months. Twelve children with CKD stage 5D received iron sucrose infusion, and no adverse reaction occurred. Conclusions:Renal anemia has a high incidence in children with CKD. Early and standardized treatment is of great significance to improve outcome of renal anemia. Venous iron infusion is a safe and effective treatment method for children with maintenance dialysis.

Objective:To analyze the risk factors of neovascular glaucoma (NVG) after 25G pars plana vitrectomy (PPV) in proliferative diabetic retinopathy (PDR).Methods:A retrospective study. From January 2017 to December 2018, 340 PDR patients (340 eyes) with vitreous hemorrhage (VH) who were first treated with PPV in Tianjin Medical University Eye Hospital were included in the study. Among them, 185 were male and 155 were female, with an average age of 55.79±10.82 years. The duration of diabetes was 13.01±7.70 years, the fasting blood glucose was 7.55±2.15 mmol/L. Nineteen patients combined coronary heart disease, and 20 patients combined cerebral infarction. All patients underwent best-corrected visual acuity (BCVA), intraocular pressure (IOP), non-contact fundus examination, and fundus color photographs. BCVA was measured using an international standard Snellen visual acuity chart, and the values were converted to logarithm of the minimum angle of resolution (logMAR) scores for data analysis. The baseline logMAR BCVA was 2.04±0.73, The baseline IOP was 15.45±2.93 mmHg (1 mmHg=0.133 kPa). The duration of VH was 2.98±1.46 months, ranged from 3 weeks to 6 months. Three hundred and forty eyes included 93 eyes of PDR Ⅳ stage (27.35%), 107 eyes of Ⅴ stage (31.47%), and 116 eyes of Ⅵ stage (34.12%), combined tractional retinal detachment (TRD) 83 eyes. All patients underwent 25G standard three channel vitrectomy through the pars plana of the ciliary body. Preoperative anti-VEGF injection was performed in 57 eyes, internal limiting membrane (ILM) peeling in 234 eyes, combined phacoemulsification cataract surgery in 262 eyes and 141 eyes intravitreal anti-VEGF injection at the end of surgery. The patients were followed up for at least 12 months, with an average follow-up time of 10.80±5.79 months. NVG was defined as the presence of neovascularization in the anterior chamber angle or iris with an IOP higher than 21 mmHg after vitrectomy. Kaplan-Meier method and Cox univariate and multivariate regression were used to analyze the relationship between baseline factors, ocular factors, surgical factors and the occurrence of NVG after surgery.Results:Among 340 eyes, 66 eyes (19.41%) developed NVG after vitrectomy during 12 months of observation, NVG occurred from 6 to 335 days after surgery, and the mean period between vitrectomy and developing NVG was 98.00±5.79 days. The incidence of NVG was 11.50%, 15.29% and 20.75%, respectively in the 3rd, 6th and 12th month after PPV. The result of univariate analysis with the Cox regression analysis showed that the development of NVG at 12 months after surgery and age, combined coronary heart disease or cerebral infarction, combined with cataract phacoemulsification, ILM peeling, preoperative anti-VEGF injection had effect on postoperative NVG ( P<0.05). Ocular factors such as PDR staging, combined TRD, preoperative logMAR BCVA, preoperative intraocular pressure, etc. had no effect on the occurrence of NVG after surgery ( P>0.05). Combined cataract phacoemulsification surgery, internal limiting membrane peeling, surgical factors such as intracavity injection of anti-VEGF drugs 3 days before surgery, had an impact on the occurrence of NVG after surgery ( P<0.05). The meaningful variables of the Cox univariate analysis were incorporated into the multivariate Cox proportional hazard model for analysis, and the influencing factors of NVG after surgery were gradually regressed. The results showed that age, coronary heart disease or cerebral infarction, combined with phacoemulsification of cataract, and internal limiting membrane removal during surgery were independent risk predictors of NVG after surgery ( P<0.05). Conclusions:Younger, coronary heart disease or cerebral infarction, combined with cataract phacoemulsification are the risk factors of NVG in PDR patients after PPV. The removal of internal limiting membrane can reduce the incidence of NVG.

According to different experimental methods of induced diabetic retinopathy (DR) and different characteristics of the observed retinopathy, DR animal models can be divided into drug or dietary-induced models, oxygen-induced retinopathy (OIR) models, spontaneous inheritance models, and transgenic models. At present, induced model is one of the most commonly used animal model for DR study, which has the advantages of short modeling cycle, low cost, simple experimental operation and good repeatability. However, the drugs have certain side effects on various organs of animals and the risk of animal death is higher. OIR model has good repeatability, good stability and relatively low cost. However, due to the lack of metabolic changes of hyperglycemia in OIR mice, this model cannot accurately reflect the effects of metabolism on retina under hyperglycemia. The pathological changes of the spontaneous model are relatively stable, however, the application of this model is limited because the genetic homogeneity of diabetes differs from that of human and the cost is high. Transgenic model has definite etiology, however, its application is limited owing to the high cost and the high requirements of technology, operation and equipment. Therefore, researchers should comprehensively consider characteristics and limitations of different models while choosing suitable DR model based on research objectives, observation indicators, experimental conditions, and funds. In addition, animal models that can more accurately simulate DR need to be developed to provide more effective tools for studying the mechanism of DR and developing feasible prevention and treatment approaches.

Objective:To characterize proteomic profile in aqueous humor of patients with high myopia using quantitative proteomic analysis.Methods:Sixty-eight age-related cataract patients were divided into high myopic cataract group and simple cataract group according to that they had high myopia or not, with 34 patients (34 eyes) in each group.Aqueous humor samples (100 μl/patient) were collected from each patient using a 1 ml tuberculin syringe during cataract surgery at Tianjin Medical University Eye Hospital from January 2019 to August 2019.Sixteen samples from each group were selected for protein quantification and comparison by BCA method.The differentially expressed proteins between the two groups were analyzed using label-free liquid chromatography tandem mass spectrometry.The function and signal transduction pathways of differentially expressed proteins were further analyzed by Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes.Eighteen aqueous humor samples from each group were selected to verify the results of mass spectrometry by enzyme-linked immunosorbent assay (ELISA). This study protocol adhered to the Declaration of Helsinki.The use of human samples was approved by an Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY[L]-40). Written informed consent was obtained from each patient prior to surgery.Results:The mean protein mass concentration of aqueous humor sample in the high myopic cataract group was (1 134.91±104.78) ng/L, which was significantly higher than that in the simple cataract group (706.71±85.43) ng/L, showing statistically significant difference ( t=11.977, P<0.01). A total of 463 proteins were identified and 86 proteins were found to be differentially expressed, including 49 up-regulated proteins and 37 down-regulated proteins in the two groups.These differentially expressed proteins were mainly protein-binding activity modulator, extracellular matrix protein, carrier protein, intercellular signal molecule, protein modifying enzyme and so on, accounting for 32.70%, 14.50%, 9.10%, 9.10% and 7.30%, respectively.Bioinformatics analysis showed that 86 differentially expressed proteins were mainly related to biological processes such as complement activation and regulation, acute inflammatory response, and extracellular matrix tissue remodeling.Among them, 21 differentially expressed proteins were enriched in the complement and coagulation cascades pathways, 15 in the extracellular matrix-receptor interaction pathway, and 8 in the PI3K-Akt signaling pathway.ELISA results showed that the expression trends of three randomly selected differentially expressed proteins of the two groups were consistent with the results of label-free quantitative proteomic analysis. Conclusions:There are significant changes in proteomic profiles of aqueous humor between the high myopia cataract patients and simple cataract patients.High myopia is closely associated with inflammation and immune interactions, and remodeling of extracellular matrix.