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.

ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste （养心达瓦依米西克蜜膏， YDMHP） in the treatment of stable angina pectoris （SAP） of qi stagnation and blood stasis syndrome. MethodsA randomized ， double-blind， positive-controlled，multi-center clinical trial was conducted， in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group（279 cases）and control group（91cases）at a ratio of 3∶1. The treatment group was orally administered with YDMHP， 3 g each time， and placebo of Xuefu Zhuyu Capsule （血府逐瘀胶囊）， 2.4 g each time， while the control group was treated with Xuefu Zhuyu Capsule， 2.4 g each time， and placebo of YDMHP， 3 g each time， both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks， duration of attacks， pain intensity and usae of nitroglycerin scores， the total angina symptom score before and after the treatment， the usage of nitroglycerin， the exercise duration in treadmill exercise test （TET） and the Duck treadmill score among patients，the scores of Seattle Angina Questionnaire （SAQ） on five dimensions including physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception， and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine， urine routine， liver and kidney function， fasting blood sugar， electrocardiogram， adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% （200/279）， significantly higher than 51.64% （47/91） in the control group （P＜0.01）. The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% （148/279）， which was significantly higher than 25.27% （23/91） in the control group （P＜0.01）. After treatment， scores of the number as well as duration of angina attacks and pain severity， the total score of angina symptoms， and the usage of nitroglycerin significantly decreased in both groups， and more changes were seen in the treatment group than in the control group； the scores of physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception in both groups significantly increased， and more improvement were shown in the experimental group regarding the anginal stability， anginal frequency and treatment satisfaction （P＜0.05 or P＜0.01）. The effects of chest pain， chest tightness， palpitation， shortness of breath and fatigue in experimental group were significantly higher than those in control group （P＜0.05 or P＜0.01）. There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment （P＞0.05）. Adverse events occurred in 66 cases （23.66%） of the experimental group and 16 cases （17.58%） of the control group， with no statistical significance between the two groups （P＞0.05）. ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris， reduce the number， duration， and intensity of attacks， decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.

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 dynamic change of depression in diabetic patients so as to provide evidence for early detection and warning of psychological problems in diabetic patients. 【Methods】 Based on the data from the China Health and Retirement Longitudinal Study （CHARLS）， the propensity score matching method was used to eliminate confounding factors in the study. The linear growth model， the nonlinear quadratic growth model， and the growth model without defined curve type were fitted respectively. According to the fitting indices of the models， the optimal solution of the growth function was determined to explore the changes of depression development in the diabetic patients. 【Results】 A total of 5 711 cases （5 380 cases in the non-diabetic group and 331 cases in the diabetic group） were included in the study. After propensity score matching， 1 621 cases （1 291 cases in the non-diabetic group and 330 cases in the diabetic group） were included and all confounding factors were balanced between the two groups. By fitting three growth curve models with latent variables， the results showed that the model without defined curve type was better than the other two models. The mean depression score for initial status in the non-diabetic and diabetic groups was 9.640 and 10.097， respectively， with significant inter-individual differences. During the follow-up period， the depression status of both groups showed a trend of decrease first and then increase， but the depression score was always lower in the non-diabetic group than in the diabetic group. At the same time， there was no individual difference in the rate of change between the two groups， and there was no statistical difference between the initial depression score and the subsequent slope of change. 【Conclusion】 Exploring the change track of depression status over time in diabetic patients， understanding the individual psychological change trend and further explaining the differences between individuals are of great significance for intervention on psychological status at different stages.

Objective:To explore the effect of cognitive behavioral intervention combined with early functional exercise on kinesiophobia in patients with lumbar disc herniation after surgery.Methods:From September 2020 to September 2021, the convenient sampling was used to select 90 patients with kinesiophobia after lumbar disc herniation surgery in Department of Orthopedics in Nanjing First Hospital as the research objects. They were divided into the intervention group and the control group by the random number table, with 45 cases in each group. The control group received routine nursing, while the intervention group received cognitive behavioral intervention combined with early functional exercise on the basis of routine nursing. The scores of Tampa Scale for Kinesiophobia (TSK) , Fear Avoidance Beliefs Questionnaire (FABQ) , Exercise Adherence Rating Scale (EARS) and Japanese Orthopaedic Association (JOA) were compared between the two groups at the time of admission, at discharge and 1 and 3 months after the operation.Results:After the intervention, the TSK and FABQ scores of the patients in the intervention group were lower than those in the control group at the time of discharge, 1 month after surgery and 3 months after surgery; the EARS and JOA scores of patients in the intervention group were higher than those in the control group at the time of discharge, 1 month and 3 months after operation, and the differences were all statistically significant ( P<0.05) . Conclusions:Cognitive-behavioral intervention combined with early functional exercise can effectively reduce the level of kinesiophobia and fear-avoidance beliefs in patients with postoperative lumbar disc herniation, improve their exercise compliance and effectively improve their physical function.

Objective:To report a newborn with Goltz syndrome and a de novo mutation in the PORCN gene. Methods:Clinical data collected from a newborn with Goltz syndrome were retrospectively analyzed. Peripheral venous blood samples were obtained from the newborn and her parents, genomic DNA was extracted, whole-exome sequencing was performed to screen disease-causing genes in the patient, and Sanger sequencing was conducted to verify the mutant genes.Results:The 7-hour-old female newborn presented with scalp defects, multiple epidermal defects on the face and inner side of both knee joints, deformity of the left auricle, syndactyly of the middle and ring fingers of the right hand as well as the great and second toes of the right foot, and lobster-claw deformity of the left foot. Genetic testing showed that a fragment TCCTTCCA was inserted at position 514-521 in exon 4 of the PORCN gene of the patient (c.514_521dupTCCTTCCA) , resulting in the substitution of serine by proline at amino acid position 175 (p.S175Pfs*14) , followed by translation termination at the 14th codon. This heterozygous mutation was not found in her parents. The patient was diagnosed with Goltz syndrome. Conclusions:There are various phenotypes of Goltz syndrome, and a confirmed diagnosis of Goltz syndrome can be made based on PORCN gene mutations and clinical manifestations. The heterozygous mutation c.514_521dupTCCTTCCA is a novel mutation.

Objective:To explore the significance of multidisciplinary team for the diagnosis and treatment of congenital band syndrome.Methods:Five children with congenital circular band syndrome admitted in the First Affiliated Hospital of the Chinese People′s Liberation Army Air Force Medical University from January 2017 to January 2020 were retrospectively analyzed.They were diagnosed, treated and followed up by a multidisciplinary team including the department of obstetrics and gynecology, ultrasound, and orthopedics from the fetal stage.Results:One case was found with gradually aggravated ring band that affects the blood circulation of distal limbs during fetal examination, who was promptly performed with partial band release under fetoscopy.All cases had Patterson type Ⅰ ring bands at birth, and distal limbs did not have obvious deformity.They were performed with selective annular band resection, and postoperatively followed up for an average of 10.6 (8-13) months.The annular depression of the skin disappeared, and the appearance and function recovered satisfactory.According to the monitoring of side effects scale (Moses), 4 cases were excellent, 1 case was good, and the excellent and good rate was 100%.Conclusions:The multidisciplinary team for the diagnosis and treatment of congenital band syndrome can maximize the professional advantages of physicians with diffe-rent specialties, make early diagnosis and treatment, minimize the compression of the ring band on the limbs, and avoid serious limb deformities.It is worthy of clinical application.

In medical research, the quality of data is the key to success. Thus, data quality control becomes an important part of ensuring the research's high quality. REDCap system is an emerging data acquisition system in medical research, which is gradually applied in research at home and abroad. It is a hot issue to realize double data entry and data quality control in using the REDCap system, which researchers are concerned about when this system is supposed to apply. This article will systematically introduce how to use the REDCap system for double data entry and quality control from the aspects of research project creation, data collection tool design, double data entry, data checking and exporting.

OBJECTIVE: To explore the genetic basis for a pedigree affected with Charcot-Marie-Tooth (CMT) disease through high-throughput sequencing. METHODS: Potential variants of the genes associated with CMT were screened by next-generation sequencing (NGS) of the members of the pedigree. RESULTS: NGS has revealed that the two affected sisters both harbored homozygous c.1A>G variant of the GDAP1 gene, which caused replacement of the first amino acid Methionine by Valine (p.Met1Val). Their parents were both carriers of the heterozygous c.1A>G variant. The variant was unreported previously and has an extremely low frequency in the population. Meanwhile, one of the sisters and the mother also carried heterozygous c.710A>T variant of the BAG3 gene. CONCLUSION The homozygous c.1A>G variant of the GDAP1 gene probably underlay the CMT in both children. Above result has enabled clinical diagnosis and genetic counseling for this pedigree.
Adaptor Proteins, Signal Transducing/genetics* ; Apoptosis Regulatory Proteins/genetics* ; Charcot-Marie-Tooth Disease/genetics* ; Child ; Female ; Fibula/abnormalities* ; Homozygote ; Humans ; Mutation ; Nerve Tissue Proteins/genetics* ; Pedigree

Objective: To identify the initial chest computed tomography (CT) findings and clinical characteristics associated with the course of coronavirus disease 2019 (COVID-19) pneumonia. Materials and Methods: Baseline CT scans and clinical and laboratory data of 72 patients admitted with COVID-19 pneumonia (39 men, 46.2 ± 15.9 years) were retrospectively analyzed. Baseline CT findings including lobar distribution, presence of ground glass opacities, consolidation, linear opacities, and lung severity score were evaluated. The outcome event was recovery with hospital discharge. The time from symptom onset to discharge or the end of follow-up (for those remained hospitalized) was recorded. Data were censored in events such as death or discharge without recovery. Multivariable Cox proportional hazard regression was used to explore the association between initial CT, clinical or laboratory findings, and discharge with recovery, whereby hazard ratio (HR) values < 1 indicated a lower rate of discharge at four weeks and longer time until discharge. Results: Thirty-two patients recovered and were discharged during the study period with a median length of admission of 16 days (range, 9 to 25 days), while the rest remained hospitalized at the end of this study (median, 17.5 days; range, 4 to 27 days). None died during the study period. After controlling for age, onset time, lesion characteristics, number of lung lobes affected, and bilateral involvement, the lung severity score on baseline CT (> 4 vs. ≤ 4 [reference]: adjusted HR = 0.41 [95% confidence interval, CI = 0.18–0.92], p = 0.031) and initial lymphocyte count (reduced vs. normal or elevated [reference]: adjusted HR = 0.14 [95% CI = 0.03–0.60], p = 0.008) were two significant independent factors that influenced recovery and discharge. Conclusion Lung severity score > 4 and reduced lymphocyte count at initial evaluation were independently associated with a significantly lower rate of recovery and discharge and extended hospitalization in patients admitted for COVID-19 pneumonia.