Objective:To study the etiological relationship between Yunnan sudden unexplained death (hereinafter referred to as YNSUD) and the desmosomal protein gene mutation of arrhythmogenic right ventricular cardiomyopathy (ARVC).Methods:From September 2019 to August 2020, a cross-sectional survey method was used to select 9 key counties (cities) of YNSUD in Yunnan Province as survey sites. Autopsy cardiac blood samples of YNSUD cases ( n = 11) were collected, and peripheral venous blood samples of co-occurring case ( n = 1), case relatives ( n = 128), and control population ( n = 60) were collected. Genomic DNA from blood was extracted. After PCR amplification, 97 exons of 5 ARVC desmosomal protein genes, including plakophilin-2 (PKP2), desmoglein-2 (DSG2), desmocollin-2 (DSC2), desmoplakin (DSP), and junction plakoglobin (JUP) were sequenced by Sanger method, and the gene mutation was analyzed. Results:Compared with the control population, YNSUD cases, co-occurring case and case relatives carried 52 gene mutation sites in 36 exons of the ARVC desmosomal protein gene, with a total mutation rate of 37.11% (36/97). Among them, there were 21 in DSP gene, 10 in DSG2 gene, 8 in PKP2 gene, 8 in DSC2 gene, and 5 in JUP gene. YNSUD cases, co-occurring case and case relatives carried two same gene mutation sites: DSG2 gene exon 15 c.3321 T>C synonymous mutation and JUP gene exon 3 c.213 T>C synonymous mutation.Conclusions:The mutation rate of ARVC desmosomal protein gene is relatively high in the population of YNSUD. The two same gene mutation sites (DSG2 gene c.3321 T>C and JUP gene c.213 T>C) carried by YNSUD cases, co-occurring case and case relatives may be associated with the pathogenesis of YNSUD.

Objective:To study the etiological relationship between Yunnan sudden unexplained death (hereinafter referred to as YNSUD) and the desmosomal protein gene mutation of arrhythmogenic right ventricular cardiomyopathy (ARVC).Methods:From September 2019 to August 2020, a cross-sectional survey method was used to select 9 key counties (cities) of YNSUD in Yunnan Province as survey sites. Autopsy cardiac blood samples of YNSUD cases ( n = 11) were collected, and peripheral venous blood samples of co-occurring case ( n = 1), case relatives ( n = 128), and control population ( n = 60) were collected. Genomic DNA from blood was extracted. After PCR amplification, 97 exons of 5 ARVC desmosomal protein genes, including plakophilin-2 (PKP2), desmoglein-2 (DSG2), desmocollin-2 (DSC2), desmoplakin (DSP), and junction plakoglobin (JUP) were sequenced by Sanger method, and the gene mutation was analyzed. Results:Compared with the control population, YNSUD cases, co-occurring case and case relatives carried 52 gene mutation sites in 36 exons of the ARVC desmosomal protein gene, with a total mutation rate of 37.11% (36/97). Among them, there were 21 in DSP gene, 10 in DSG2 gene, 8 in PKP2 gene, 8 in DSC2 gene, and 5 in JUP gene. YNSUD cases, co-occurring case and case relatives carried two same gene mutation sites: DSG2 gene exon 15 c.3321 T>C synonymous mutation and JUP gene exon 3 c.213 T>C synonymous mutation.Conclusions:The mutation rate of ARVC desmosomal protein gene is relatively high in the population of YNSUD. The two same gene mutation sites (DSG2 gene c.3321 T>C and JUP gene c.213 T>C) carried by YNSUD cases, co-occurring case and case relatives may be associated with the pathogenesis of YNSUD.

Objective:To observe and analyze the macular microvascular system changes in unilateral pediatric uveitis (PU) and healthy contralateral eyes.Methods:A cross-sectional case-control study. From January 2019 to July 2021, 21 eyes of 21 patients with PU diagnosed in one eye (PU group), 21 unaffected contralateral eyes (contralateral eye group), and 21 age-matched volunteers with 21 eyes (NC group) during the same period were examined in Peking Union Medical College Hospital. Optical coherence tomography angiography was used to scan the 6 mm × 6 mm fundus macular area in the three groups of selected eyes to measure the vessel density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of the retina, the area of the avascular zone (FAZ) in the fovea of the macula, the choroidal thickness under the fovea (SFCT), and the retinal thickness in the fovea of the macula (CRT). The device comes with a software choriocapillary flow measurement tool, which can obtain the macula's choriocapillary density (CCD) with the fovea as the center and the diameter of the annular area of 1.0 mm, 1.5 mm, and 3.0 mm, respectively. They were recorded as CCD-1.0, CCD-1.5, and CCD-3.0. The measurement data of multiple groups were compared by analysis of variance; if the variance of the three groups of data was not uniform, the Kruskal-Wallis test was used. Multiple linear regression analysis was used to evaluate the potentially related factors of CCD.Results:Compared with the contralateral eye group and the NC group, the vessel density of SCP ( H=-13.857,-25.500; P=0.043, P<0.001), DCP ( H=-15.333, -31.595; P=0.007, P<0.001) and CCD-1.0 ( H=-14.000,-16.214; P=0.040, 0.012) of the clinically quiescent PU group were significantly decreased. CRT and FAZ were not statistically different between PU and NC groups ( F=0.955; P=1.000, 0.661). Compared with the NC group, the mean vessel density of SCP and DCP in the contralateral eye group decreased, and the difference in DCP vessel density was statistically significant ( H=-16.262, P=0.004). There was no statistically significant difference between the CCD of two groups ( P=1.000). The SFCT of the PU group was significantly thicker than that of the NC group ( F=5.552, P=0.004), however, difference was not statistically significant from the fellow eye group ( F=5.552, P=0.270). The results of multiple linear regression analysis revealed that the CCD-1.0, CCD-1.5, and CCD-3.0 showed a linear correlation with the area of FAZ ( β=-0.494, -0.527, -0.566; P=0.015, 0.009, 0.010) and CRT ( β=-0.322, -0.466, -0.342; P=0.026, 0.002, 0.028). CCD-1.0 and CCD-1.5 showed a linear correlation with the vessel density of DCP ( β=0.277, 0.275; P=0.047, 0.045). Conclusion:Both retinal and choroidal microvasculature are abnormal in resting eyes with PU, and macular circulation disorders may be present in the unaffected fellow eye.

Objective: To evaluate the reliability and validity of a questionnaire for job satisfaction with influenza vaccine recommendation of community diabetes management doctors. Methods: Through the literature review,expert interviews and pilot survey,a questionnaire for job satisfaction with influenza vaccine recommendation of community diabetes management doctors was initially formed. Cronbach's α coefficient was used to evaluate the reliability of the questionnaire; correlation analysis,exploratory factor analysis（EFA）and confirmatory factor analysis（CFA）were used to evaluate the validity of the questionnaire. Results : The questionnaire had 23 items, which were categorized into four dimensions: working environment,job itself,general satisfaction and occupational load. The Cronbach's α coefficient of working environment,job itself,general satisfaction, occupational load and the total questionnaire was 0.924,0.884,0.937,0.891 and 0.936,respectively. EFA showed that the characteristic roots of four dimensions were all more than one,and the cumulative variance proportion was 73.82%. The Pearson correlation coefficient between each item and the total questionnaire ranged from 0.339 to 0.818, and the correlation coefficient between each dimension and the total questionnaire ranged from 0.429 to 0.872（all P<0.05）. CFA showed that the variances of parameter estimation errors were all positive,and the standard errors ranged from 0.035 to 0.099,which were statistically significant（P<0.05）;the standardized parameters between each item and dimension ranged from 0.596 to 0.939; χ2/df was 4.627（P<0.05）, the comparative fit index was 0.827,the root mean square error of approximation was 0.076,which indicated the model fit. Conclusion The questionnaire has good reliability and validity,so it can be used to evaluate the satisfaction with influenza vaccine recommendation of community diabetes management doctors.

The increasing use of target therapy and immunocheckpoint inhibitors in cancers has brought new hope of survival to patients with advanced tumors. However, more and more adverse side-effects and toxicities of these medications had been reported, affect almost all human organs including the eye. These adverse effects may affect the entire ocular tissues, like eyelid, eye lashes, conjunctiva, cornea, uvea, retina, optic nerve and so on, which are always been ignored by patients and doctors. In this paper we will summarize the characteristics of the related ocular diseases and give our advice on how to diagnose and manage these diseases.

Objective To explore the effects of transcutaneous electrical acupoint stimulation (TEAS) on upper limbs function in chronic stroke patients. Methods From March, 2016 to May, 2018, 53 patients were randomly divided into control group (n = 27) and research group (n = 26). All the patients received conventional rehabilitation, and the research group received additional intervention of TEAS, for six weeks. They were assessed with Manual Muscle Test (MMT) on upper limbs, modified Ashworth Scale (MAS), Fugl-Meyer Assessment-upper extremities (FMA-UE), Hand Motor Status Scale and modified Barthel Index (MBI) before, at the end of 6-week treatment and twelve weeks after treatment. Results There was no significant difference in all the scores between two groups at the end of 6-week treatment (t < 1.511, P > 0.05). The scores of MMT of wrist dorsal extension, FMA-UE and MBI were better in the research group than in the control group twelve weeks after end of treatment (t > 2.312, P < 0.05). Conclusion TEAS may promote the recovery of hands and upper limbs function in chronic stroke patients.

Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveitis. Although systemic corticosteroids have been the gold standard of immunosup- pressive treatment for uveitis since first introduced in 1950s, its side effects of long-term use often warrant an adjuvant treatment to reduce the dosage/duration of corticosteroids needed to maintain disease control. Conventional immunosuppressive drugs, classified into alkylating agent, antimetabolites and T cell inhibitors, have been widely used as corticosteroid-sparing agents, each with characteristic safety/tolerance profiles on different uveitis entities. Recently, biologic agents, which target specific molecules in immunopathogenesis of uveitis, have gained great interest as alternative treatments for refractory uveitis based on their favorable safety and effectiveness in a variety of uveitis entities. However, lack of large randomized controlled clinical trials, concerns about efficacy and safety of long-term usage, and economic burden are limiting the use of biologics in non-infectious uveitis. Local administration of immunosuppressive drugs (from corticosteroids to biologics) through intraocular drug delivery systems represent another direction for drug development and is now under intense investigation, but more evidences are needed to support their use as regular alternative treatments for uveitis. With the numerous choices belonging to different treatment modalities (conventional immunosuppressive agents, biologics and local drug delivery systems) on hand, the practice patterns have been reported to vary greatly from center to center. Factors influence uveitis specialists' choices of immunosuppressive agents may be complex and may include personal familiarity, treatment availability, safety/tolerability, effectiveness, patient compliance, cost concerns and suggestions from related specialists such as rheumatologists and pediatricians. The focus of this review is to provide an overview of each treatment modality on safety/tolerability and effectiveness, which are believed to be the two most important factors affecting treatment decision making.
Humans ; Immunosuppression ; methods ; Immunosuppressive Agents ; therapeutic use ; Uveitis ; immunology ; pathology ; therapy

Objective To study the ocular manifestations in patients with Behcet's disease (BD).Methods Medical records at Peking Union Medical College Hospital from 2002 to 2012 were reviewed to identify the patients who were diagnosed as BD with ocular involvement.Results One hundred and eleven BD patients developed ocular involvement.Males were more frequently involved,and the male/female ratio was 2.08∶ 1.The age at the onset of BD and the time of ocular involvement were (27.6-± 10.8) and (31.5 ± 10.7) years,respectively.The median interval between the diagnosis of BD and ocular disease was 24 (0,372) months.Ocular involvement was bilateral in 85.6％ patients.About two thirds patients (66.7％) had impaired vision,for example,visual acuity of 0.1 or less was detected in 60.4％ patients.Uveitis (90.1％) was the most common findings in BD patients with ocular involvement and the most frequent type of uveitis in both sexes was panuveitis (62.16％).Vision loss,proliferative retinopathy and cataract were more common in men.There was a statistically significantly higher frequency of positive human leukocyte antigen(HLA)-B51 in the male BD with ocular involvement than in the female.All BD patients with uveitis were given systemic corticosteroid or combined immunosuppressive agents.The improvement of visual acuity was seen in 77％ BD patients,but the recurrent attacks occurred in 49％ patients,resulting in blindness in 25.5％ of them.TNFα blockers were given to 19 recurrent uveitis patients,12 patients improved while two had no response.Conclusions The most common ocular involvement in BD was uveitis.Males were more frequently involved with a more severe disease,higher complications and positive HLA-B51 than in females.Glucocorticoids and immunosuppressants were effective to uveitis,but high rate of recurrent inflammatory ocular attacks led to high risk of blindness.TNFα blockers may improve the outcome of recurrent BD uveitis.

ObjectiveTo investigate the effect of tacrolimus (FK506) on macrophage accumulation,proliferation and activation in the kidney of early diabetic rats and to explore its possible mechanism of renal protection.Methods Rats were randomly divided into control,model and tacrolimus groups.Diabetic model rats were induced with intraperitoneal injection of streptozotocin.Tacrolimus(0.5 or 1.0 mg·kg-1 ·d-1) was orally administered once a day for 4 weeks.Kidney weight index(KWI),24-h urinary albumin excretion rate(UAER) and creatinine clearance rate(Ccr) were measured.Kidney pathology was observed by light microscopy.ED-1,PCNAandiNOSpositivemacrophagesweredetectedbysingleanddoublestainingof immunohistochemistry.Results KWI increased in model group and was significantly reduced by tacrolimus treatment with 1.0 mg·kg-1 ·d-1 (P＜0.05).UAER elevated in model group and was markedly attenuated by tacrolimus treatment with 0.5 and 1.0 mg·kg-1 ·d-1 (P＜0.05).Elevated glomerular volume of model rats was significantly decreased by tacrolimus treatment with 0.5 and 1.0 mg·kg-1·d-1 (P＜0.05),and increased indices of tubulointerstitial injury were only ameliorated by 1.0 mg·kg-1·d-1 tacrolimus(P＜0.01).Marked accumulation of ED-1+ cells in diabetic kidney was found,which was not inhibited by tacrolimus treatment with 0.5 and 1.0 mg·kg-1·d-1.ED-1PCNA+ cells and ED-1+ iNOS+ cells were significantly elevated in kidneys of model group,while they were significantly inhibited by tacrohmus treatment with 0.5 and 1.0 mg·kg-1·d-1 (P＜0.01).Conclusion Tacrolimus can ameliorate early renal injury of diabetic rats and its mechanism may be partly associated with the suppression of increased macrophages activation.