Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.

Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent proteinuria and progressive decline in renal function, and is one of the microvascular complications of diabetes. With the in-depth understanding of the pathogenesis of DN, the role of intestinal flora imbalance in the disease has been found clinically. This suggests that restoring the host′s healthy gut flora may be a means of improving DN. In fact, recent studies have shown that many of the drugs currently used to treat DN affect gut microbiota composition. In this review, intestinal flora is regarded as one of the main factors affecting the development of DN, and DN therapy targeting intestinal flora is summarized to provide new ideas for the diagnosis and treatment of DN.

Objective:To explore the mediating effect of carotid atherosclerosis on serum triglyceride-glucose (TyG) index and silent lacunar infarction (SLI) in non-diabetic population.Methods:A total of 2 482 patients were selected from the Health Examination Center of Hebei General Hospital from January 2019 to December 2021. The basic demographic information, biochemical parameters, calculated TyG index and carotid plaque score were collected. SLI was diagnosed according to the criteria formulated by Chinese Society of Neurology. Participants were divided into SLI group and non-SLI group according to whether there was SLI in brain magnetic resonance imaging, and the non-SLI group was normal without lacunar infarction. Spearman correlation analysis was used to explore the correlation between TyG index and carotid plaque score. Binary Logistic regression analysis was used to analyze the effects of TyG index and carotid plaque score on SLI. Bootstrap was used to explore whether carotid plaque score mediated the association between TyG index and SLI.Results:There were 471 patients (18.98%) who had SLI, and 2 011 patients (81.02%) did not. Carotid plaque score [2(0, 5) vs 1(0, 3)] and TyG index [7.17(6.81, 7.64) vs 7.12(6.77, 7.54)] were increased in the SLI group compared with the non-SLI group ( Z=-4.213, Z=-2.636, P<0.05). Spearman correlation analysis showed that carotid plaque score was positively correlated with TyG index ( r=0.083, P<0.001). Multivariate Logistic regression analysis indicated that carotid plaque score ( OR=1.047, 95% CI 1.002-1.094) and TyG index ( OR=1.329, 95% CI 1.106-1.598) were independent risk factors for SLI ( P<0.05). Mediated effect analysis showed that TyG index had a direct effect on the incidence of SLI (β=0.265, 95% CI 0.102-0.428). Carotid plaque score partially mediated the effect of TyG index on the incidence of SLI (β=0.024, 95% CI 0.009-0.043), and the mediating effect accounted for 8.30% of the total effects. Conclusion:In non-diabetic population, TyG index and carotid plaque score are predictors of SLI, and the carotid plaque score is a partial mediator in the effect of TyG index on the incidence of SLI.

There are some issues in the process of patient treatment in the medical field, such as knowledge inequality, difficulties in doctor-patient trust and interdisciplinary cooperation, disciplinary barriers, excessive diagnosis and treatment, and structural imbalance of medical resources. In response to these issues, combined with the advantages of conceptual integration, professional integration, and resource integration of medical social work, this paper proposed a practical path for integrating medical social work services in the medical field. The main paths include micro path that systematization, comprehensiveness, and personalization of patient’s diagnosis and treatment process, the integration of intermediary path that integration of disciplinary and professional perspectives, concepts, and practices, and macro path that collaboration and coordination among society, community, and healthcare systems.

Systemic lupus erythematosus (SLE) is a serious autoimmune disease that affects multiple systems and organs throughout the body. Thrombotic microangiopathy (TMA) is a rare clinical syndrome that can lead to multiple organ dysfunction and even threaten life. Clinically, SLE patients with TMA are relatively rare, especially in children, but the mortality of SLE patients with TMA is significantly increased. The article reports 2 cases of successful remission of SLE complicated with TMA after treatment with eculizumab, and discusses the diagnosis, clinical manifestations and treatment of SLE complicated with TMA in children, so as to provide clinical basis for the diagnosis and treatment of SLE complicated with TMA in children.

Cohort study is one of the important research methods in analytical epidemiology because of its clear time sequence relationship, which is better than other observational studies in demonstrating causal association. However, screening diagnosis or other methods are often used to exclude the individuals with outcome events during the enrollment process of the subjects in cohort studies. The accuracy of screening diagnosis and the effectiveness of exclusion will affect the accuracy of the baseline status assessment of the subjects included in the study, which may lead to the causal time sequence reversal of exposure-outcome in the estimation of causal effect. Landmark analysis can be used to control reverse causality by excluding subjects with potentially unknown expose-outcome timing. In this paper, we describe the basic principles and analytical steps of landmark analysis, and use data from the Chinese Longitudinal Healthy Longevity Survey to explore the relationship between physical activity and frailty, and introduce the specific application of landmark analysis for the purpose of facilitating its application and inferring causal effects more accurately in cohort studies.

With completing a baseline survey of a large natural population cohort, conducting regular follow-up has become a key factor in further improving the quality of cohort construction and ensuring its sustainable development. Typical cohort follow-up methods include repeat surveys, routine monitoring, and community-oriented surveillance. However, in practical applications, there are often issues such as high costs, difficulty, and high error rates. Telephone follow-up is an important supplementary method to the methods mentioned above, as it has the characteristics of low cost, fast response, and high quality. However, the with difficult organization, quality control is challenging, response rates are low, and management levels vary widely, which limits its widespread use in large-scale population cohort studies. Given the above problems, this study draws on customer relationship management based on the actual needs of the China Northwest Cohort follow-up. It relies on the REDCap electronic data collection platform to build a telephone follow-up management and quality control system. Targeted solutions are provided for key issues in telephone follow-up implementation, including organizational structure, project management, data collection, and process quality control, to improve the quality control level of telephone follow-up comprehensively and thereby enhance the quality and efficiency of follow-up. We hope to provide standardized follow-up programs and efficient quality control tools for newly established and existing cohort studies.

【Objective】 To clarify the hematological characteristics and current situation of chronic mountain sickness among Tibetan residents in extreme high altitude area (more than 5 000 m above the sea level) of Ali district based on the analysis of physical examination and blood test results. 【Methods】 Totally 250 Tibetan residents were selected by convenient sampling for blood oxygen saturation (SpO2), heart rate, and blood routine examination. Chronic mountain sickness was determined according to the hemoglobin (Hb) level and SpO2. 【Results】 The red blood cell (RBC), Hb and hematocrit (HCT) of the Tibetan residents at 5 200-meter altitude were all higher than the normal physiological reference range of China. Mean red blood cell volume (MCV), mean red blood cell hemoglobin content (MCH), mean red blood cell hemoglobin concentration (MCHC), white blood cell (WBC) and platelet (PLT) were in the upper limit of the reference value. The RBC, Hb, HCT and MCHC of male Tibetan residents were higher than those of females, while PLT was lower than that of females, with significant differences. There were no statistical differences in MCV, MCH or WBC among different genders of Tibetan residents. The SpO2 of the Tibetan residents was about 85% of the normal value, and the males had higher SpO2 than the females in the same age group, and the difference was statistically significant, but the heart rate did not differ significantly. The prevalence rate of chronic mountain sickness in this area was as high as 16.4%, and the prevalence rate of heavy manual workers was significantly higher than that of light manual workers, with significant differences. 【Conclusion】 The high-altitude anoxic environment causes the changes in red blood cells, hemoglobin, and oxygen saturation of local residents, and the prevalence of chronic mountain sickness increases significantly. Labor intensity is one of the risk factors for chronic mountain sickness in high-altitude areas.

Objective: To explore latent classes of college students aggressive behavior and its correlations with family care and the meaning of life among college students. Methods: A cross sectional questionnaire survey was conducted among 5 094 students from three universities in Xinxiang City in December 2021, using Aggression Questionnaire (AQ), Family APGAR Index (APGAR), and the Meaning in Life Questionnaire (MLQ). Results: Aggressive behavior of college students was classifed into three potential categories:low aggressive behavior group (26.4%), moderate aggressive behavior group (48.5%), and high aggressive behavior group(25.1%). There were significant differences in latent classes of aggressive behavior among college students by gender, physical flexibility, exercise frequency, and sleep status ( χ 2=63.95, 169.86, 125.76, 325.24, P <0.01). There were significant differences in the sense of life meaning and the degree of family care among the 3 potential categories of aggressive behavior ( F=113.47, 231.82, P <0.01). The multivariate Logistic regression analysis showed that the sense of meaning of life ( OR =0.96, 95% CI =0.96-0.97) and family care ( OR =0.83, 95% CI =0.81-0.84) were significantly associated with three classes of aggressive behavior ( P <0.01). Conclusion Aggressive behavior among college students is associated with gender, exercise frequency, sleep status, meaning of life, family care, and physical flexibility. School, family and society should actively pay attention to students psychological characteristics and to provide corresponding support for aggressive behavior prevention and intervention.

Objective:To investigate the epidemiological and clinical characteristics of visceral leishmaniasis (VL) in children, and to analyze the distinguishing features of VL associated hemophagocytic lymphohistiocytosis (HLH), so that to provide reference for the diagnosis and treatment of VL.Methods:Forty-one children with VL admitted to Xi′an Children′s Hospital from July 2012 to June 2021 were enrolled. The clinical data were retrospectively analyzed, including epidemiology, clinical manifestations, laboratory data, diagnostic methods, treatment regimens and outcomes. The patients were divided into VL group and VL+ HLH group according to whether combined with HLH or not, and the clinical characteristics and laboratory findings of the two groups were compared. Two independent samples t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:Forty-one children with VL were from different provinces, including Shaanxi Province (70.73%(29/41)), Gansu Province (14.63%(6/41)), Shanxi Province (12.20%(5/41)) and Ningxia Hui Autonomous Region (2.44%(1/41)), and 87.80%(36/41) of them lived in rural areas. The peak age was >1.0 to 3.0 years old (63.41%(26/41)). They were sporadic throughout the year. The main clinical manifestations included fever (97.56%(40/41)), splenomegaly (95.12%(39/41)), lymphadenopathy (82.93%(34/41)) and hepatomegaly (60.98%(25/41)). The numbers of cases that Leishman-Donovan bodies were detected in the first, second and third bone marrow smears were 36, four and one, respectively. Anemia, thrombocytopenia and leukopenia detected by blood routine test were 100.00%(41/41), 78.05%(32/41) and 58.54%(24/41), respectively. There were statistically significant differences in the platelet count, lactate dehydrogenase, alanine aminotransferase, triglycerides, fibrinogen and ferritin between VL group (28 cases) and VL+ HLH group (13 cases) ( t=-2.56, t=2.64, Z=-2.66, t=7.15, t=-5.76 and t=3.86, respectively, all P<0.050). The proportions of hepatomegaly and hemophagocytes found in the bone marrow smears in VL group were both lower than those in VL+ HLH group, and the differences were both statistically significant ( χ2=4.47 and 10.93, respectively, both P<0.050). Twelve cases with VL+ HLH were treated with antimony (for six days) and intravenous immunoglobulin, and the others were treated with antimony only. The cure rates of the patients treated with antimony for one and two courses were 92.68%(38/41) and 4.88%(2/41), respectively. The dose of antimony was increased one third and treatment course was prolonged to eight days in one cured case. After (41.36±31.49) months of follow-up, three cases recurred after five to eight months of cure and all of them were cured after one more course of treatment with antimony. Conclusions:Children with VL are mainly distributed in rural areas. The common clinical manifestations are fever and involvement of reticuloendothelial system, which are not specific. The positive rate of Leishman-Donovan bodies found in bone marrow smears is high, and a few negative cases need repeated bone marrow aspiration. Standardized treatment with antimony for VL in children is effective, and combination therapy with immunoglobulin can be considered if patients with VL associated HLH. Very few cases may recur and antimony is still effective.