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.

Objective Kisspeptin,a protein encoded by the KISS1 gene,functions as an essential factor in suppressing tumor growth.The intricate orchestration of cellular processes such as proliferation and differentiation is governed by the Notch1/Akt/Foxo1 signaling pathway,which assumes a central role in maintaining cellular homeostasis.In the specific context of this investigation,the focal point lies in a meticulous exploration of the intricate mechanisms underlying the regulatory effect of kisspeptin on the process of endometrial decidualization.This investigation delves into the interplay between kisspeptin and the Notch1/Akt/Foxo1 signaling pathway,aiming to elucidate its significance in the pathophysiology of recurrent spontaneous abortion(RSA).Methods We enrolled a cohort comprising 45 individuals diagnosed with RSA,who were admitted to the outpatient clinic of the Reproductive Center at the Second Affiliated Hospital of Soochow University between June 2020 and December 2020.On the other hand,an additional group of 50 women undergoing elective abortion at the outpatient clinic of the Family Planning Department during the same timeframe was also included.To comprehensively assess the molecular landscape,Western blot and RT-qPCR were performed to analyze the expression levels of kisspeptin(and its gene KISS1),IGFBP1(an established marker of decidualization),Notch1,Akt,and Foxo1 within the decidua.Human endometrial stromal cells(hESC)were given targeted interventions,including treatment with siRNA to disrupt KISS1 or exposure to kisspeptin10(the bioactive fragment of kisspeptin),and were subsequently designated as the siKP group or the KP10 group,respectively.A control group comprised hESC was transfected with blank siRNA,and cell proliferation was meticulously evaluated with CCK8 assay.Following in vitro induction for decidualization across the three experimental groups,immunofluorescence assay was performed to identify differences in Notch1 expression and decidualization morphology between the siKP and the KP10 groups.Furthermore,RT-qPCR and Western blot were performed to gauge the expression levels of IGFBP1,Notch1,Akt,and Foxo1 across the three cell groups.Subsequently,decidualization was induced in hESC by adding inhibitors targeting Notch1,Akt,and Foxo1.The expression profiles of the aforementioned proteins and genes in the four groups were then examined,with hESC induced for decidualization without adding inhibitors serving as the normal control group.To establish murine models of normal pregnancy(NP)and RSA,CBA/J×BALB/c and CBA/J×DBA/2 mice were used.The mice were respectively labeled as the NP model and RSA model.The experimental groups received intraperitoneal injections of kisspeptin10 and kisspeptin234(acting as a blocker)and were designated as RSA-KP10 and NP-KP234 groups.On the other hand,the control groups received intraperitoneal injections of normal saline(NS)and were referred to as RSA-NS and NP-NS groups.Each group comprised 6 mice,and uterine tissues from embryos at 9.5 days of gestation were meticulously collected for observation of embryo absorption and examination of the expression of the aforementioned proteins and genes.Results The analysis revealed that the expression levels of kisspeptin,IGFBP1,Notch1,Akt,and Foxo1 were significantly lower in patients diagnosed with RSA compared to those in women with NP(P<0.01 for kisspeptin and P<0.05 for IGFBP1,Notch1,Akt,and Foxo1).After the introduction of kisspeptin10 to hESC,there was an observed enhancement in decidualization capability.Subsequently,the expression levels of Notch1,Akt,and Foxo1 showed an increase,but they decreased after interference with KISS1.Through immunofluorescence analysis,it was observed that proliferative hESC displayed a slender morphology,but they transitioned to a rounder and larger morphology post-decidualization.Concurrently,the expression of Notch1 increased,suggesting enhanced decidualization upon the administration of kisspeptin10,but the expression decreased after interference with KISS1.Further experimentation involved treating hESC with inhibitors specific to Notch1,Akt,and Foxo1 separately,revealing a regulatory sequence of Notch1/Akt/Foxo1(P<0.05).In comparison to the NS group,NP mice administered with kisspeptin234 exhibited increased fetal absorption rates(P<0.001)and decreased expression of IGFBP1,Notch1,Akt,and Foxo1(P<0.05).Conversely,RSA mice administered with kisspeptin10 demonstrated decreased fetal absorption rates(P<0.001)and increased expression levels of the aforementioned molecules(P<0.05).Conclusion It is suggested that kisspeptin might exert its regulatory influence on the process of decidualization through the modulation of the Notch1/Akt/Foxo1 signaling cascade.A down-regulation of the expression levels of kisspeptin could result in suboptimal decidualization,which in turn might contribute to the development or progression of RSA.

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.

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.

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.

【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.