Objective This study aimed to identify differentially methylated genes (DMGs) associated with natural killer cells in patients with autoimmune thyroiditis (AIT),focusing on the influence of varying water iodine exposure levels. Methods Participants were divided into categories based on median water iodine (MWI) concentrations:iodine-fortified areas (IFA,MWI<10 μg/L),iodine-adequate areas (IAA,40 ≤ MWI ≤ 100μg/L),and iodine-excessive areas (IEA,MWI>300 μg/L). A total of 176 matched AIT cases and controls were recruited and divided into 89,40,and 47 pairs for IFA,IAA,and IEA,respectively. DMGs were identified using 850K BeadChip analysis for 10/10 paired samples. Validation of DNA methylation and mRNA expression levels of the DMGs was conducted using MethylTarget? and QRT-PCR for 176/176 paired samples. Results KLRC1,KLRC3,and SH2D1B were identified as significant DMGs. Validation revealed that KLRC1 was hypomethylated and highly expressed,whereas KLRC3 was hypermethylated and highly expressed in individuals with AIT. Furthermore,KLRC1 was hypomethylated and highly expressed in both IFA and IEA. Conclusion The DNA methylation status of KLRC1 and KLRC3 may play crucial roles in AIT pathogenesis. Additionally,DNA methylation of KLRC1 seems to be influenced by different iodine concentrations in water.

Based on literature research and Delphi method, the curative effect evaluation criteria of Traditional Chinese Medicine (TCM) edema were revised, in order to promote the standardization construction of the curative effect evaluation of edema and strengthen the research on the revision technology of TCM standards. From January 1, 1994 to July 1, 2021, the China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (Chongqing VIP), Chinese Academic Periodical Database (Wanfang Data) and Chinese Biomedical Literature Service System (SinoMed) were searched, and 221 articles were included. Then the questionnaire item pool was constructed after extracting the contents of the articles. Delphi method was used to conduct two rounds of expert questionnaire survey. And then the concentration degree and coordination degree of expert opinions were counted and analyzed to screen out the content to be revised and the indicators to be included in the revised version, so as to form the revised version of curative effect evaluation criteria of edema. A total of 32 experts participated in this study, and the positive coefficient of experts in the first round was 84.21%, and the positive coefficient of experts in the second round was 78.13%. The mean value ( Xˉ), full score ratio, rank sum, coefficient of variation ( CV), Kendall's coefficient of concordace (Kendall's W) were used to select the questionnaire items. Kendall's W of the second round of expert questionnaire survey was 0.368, P=0.000, higher than that of the first round, and 11 items were finally included in the curative effect evaluation. The CV of the included items in the second round of the questionnaire is lower than that in the first round, and Kendall's W was higher than that in the first round, and the expert opinions tend to be unified. Consensus was reached after the expert discussion meeting, and the revised version of curative effect evaluation criteria of edema has been preliminarily formed.

Objective:Applying bibliometrics to analyze the research history, hotspots and trends of Traditional Chinese Medicine (TCM) interventions in edema-related diseases, and to provide reference for the revision of diagnostic and therapeutic criteria for edema in TCM.Methods:The literature about edema treated with TCM was retrieved from CNKI, Wanfang, VIP, CBM from 1 st. Jan 1995 to 25 th. May 2022. CiteSpace and VOSviewer softwares were used to draw the knowledge map, and analyze the co-occurrence relationship and clustering characteristics of the institution, author, keywords and mechanism hotspots. Results:Totally 3 198 articles were included. The annual number of documents issued generally shows a spiral rise trend. Liaoning University of Chinese Medicine published the most articles. Core authors published the most articles were Sun Wei (13 articles); the team with the highest cooperation intensity was Yang Hongtao's team; keywords formed 7 clusters. Hotspot mechanisms included metabolic disorders, immune balance, anti-inflammation, calcium and phosphorus metabolism. Keywords in the past 7 years were membranous nephropathy, chronic heart failure, diabetes, lymphedema etc.Conclusions:The attention paid to the intervention of TCM in the field of edema is generally on the rise, and has decreased in the past two years. The research categories focus on the experience of famous doctors, clinical trials, and mechanistic studies, and nephropathy-related edema has been the focus of research; diabetic nephropathy, chronic heart failure, metabolomics, and immunotherapy are expected to be the focus of attention in the next stage.

Objective:To analyze the efficacy evaluation criteria of the existing TCM treatment for edema RCT research, and to provide reference for the construction of unified standards.Methods:The batabases CNKI, WanFang Data, VIP, CBM, Pubmed and Web of Science were retrieved. The randomized controlled trials for the treatment of edema of TCM research, from September 1, 1993 to July 31, 2022, were screened and included. The content of efficacy evaluation, performed statistics on evaluation standard, the curative effect evaluation indexes, as well as standard composition, usage were extracted. We analyzed the characteristics, application and problems of the existing efficacy evaluation criterion.Results:A total of 123 Chinese articles were included. The included literature involved nephrogenic edema, cardiogenic edema, idiopathic edema, apoplexy limb edema and other edema. In recent years, randomized controlled trials on the treatment of edema by TCM have mainly used four efficacy evaluation criteria. Of which the Guidelines for Clinical Research on New Chinese Medicines (Trial) in 2002 had the highest utilization rate of 29.27%. Secondly, the utilization rate of Standard for Diagnosis and Curative Effect of TCM Diseases and Syndromes was 21.14%. The rest of the criteria were used by less than 6%. While 39.02% of the literature did not use the standards or used self-designed standards. Among the composition of efficacy evaluation indices, the application rate of TCM syndrome or symptom efficacy index was the highest (91.87%), the utilization rate of the Minnesota Living with Heart Failure Questionnaire Indicators was only 4.88%; biochemical tests accounted for a large proportion of Western medical indicators, while the measurement of edema severity was rarely applied. Conclusions:At present, the evaluation criteria of edema curative effect are diversified and insufficiently popularized, which need to be further screened and improved. It is suggested to construct a TCM edema efficacy evaluation model based on the characteristics of edema syndrome, comprehensively evaluate the efficacy from multiple dimensions such as TCM syndromes, western medicine indicators, and quality of life, and improve the scientific indicators.

Objective:To explore the innovation mode of independent transformation-oriented science and technology research program approval by medical new research & development (R&D) institution.Methods:Through analyzing the program layout, funds, review experts, undertaking units, chief experts and interdisciplinarity to summarize the experiences of the independent transformation-oriented municipal program approval by Haihe laboratory of Cell Ecosystem in 2022.Results:As a new medical R&D institution, which vigorously constructed by Tianjin, Haihe laboratory of Cell Ecosystem has carried out the practice of the independent transformation-oriented municipal program through the measures of layout of full-chain transformation, conducting transformation-oriented review, gathering high-level research talents, and emphasizing interdisciplinarity.Conclusions:The experiences of Haihe laboratory of Cell Ecosystem make significance for medical new R&D institutions to explore and cultivate scientific research program with transformation potential and to promote the transformation of scientific and technological achievements, which are powerful factors for new R&D institutions to play a role of pilot and provide important support to scientific and technological innovation and transformation.

Objective:To investigate the prognostic factors of community-acquired pneumonia(CAP)in the elderly.Methods:Clinical and laboratory data of elderly patients(≥65 years old)hospitalized for CAP in the Department of Respiratory and Critical Care Medicine of Beijing Hospital from January to December 2019 were retrospectively analyzed.The patients were followed up after discharge.The patients were divided into a death group and a survival group according to their prognosis, and long-term mortality risk factors were analyzed by Cox regression.Results:A total of 118 elderly patients hospitalized for CAP with a male-to-female ratio of 1∶1 were included.The follow-up period was 20.7-39.0 months, with a median follow-up time of 29.8 months.The all-cause cumulative mortality rates at 1-2, 3, 6, 12, 24, and 36 months after discharge were 3.4%(4/118), 4.2%(5/118), 5.1%(6/118), 9.3%(11/118), 16.1%(19/118), and 21.6%(24/118), respectively.Pneumonia was the leading cause of death.Multifactorial Cox regression indicated that the Charlson comorbidity index score( HR=1.42, 95% CI: 1.11-1.83, P=0.006), the score of activities of daily living at discharge( HR=0.44, 95% CI: 0.23-0.84, P=0.013), body mass index( HR=0.83, 95% CI: 0.72-0.97, P=0.012), and the level of serum albumin( HR=0.84, 95% CI: 0.73-0.98, P=0.031)were independently associated with long-term mortality. Conclusions:The leading cause of long-term death for elderly CAP patients after discharge is pneumonia.High Charlson comorbidity index scores, lower BMI, low serum albumin levels and low scores of activities of daily living at discharge are independent risk factors for long-term mortality in these patients.Therefore, in order to reduce the occurrence of adverse prognosis and improve the quality of life, a multidimensional, comprehensive assessment and timely intervention should be performed during the acute phase of the disease.

Objective:To clarify the relationship between interleukin (IL)-6, IL-10 gene polymorphisms and autoimmune thyroid disease (AITD).Methods:Literature search was conducted through databases such as PubMed, Web of Science, CNKI, Embase, Wanfang Database and VIP.com, and domestic and foreign literatures related to IL-6, IL-10 gene polymorphisms and AITD were included in the study. The time limit was from the self-built of the databases to July 2021. Meta-analysis was performed with STATA 16.0 software, the odds ratio ( OR) and 95% confidence interval ( CI) were used as effect indicators, random-effect or fixed-effect model was selected according to the heterogeneity results, and the source of heterogeneity was explored through subgroup analysis. Publication bias was assessed using funnel plots and Egger's test. Results:Finally, 19 literatures were included, all in English. There were 12 studies on IL-6 genes and 11 studies on IL-10 genes, including 4 studies on both IL-6 and IL-10 genes. In the whole population, the loci associated with AITD were IL-6 -174 G/C site (GG vs CC + GC: OR =1.94, 95% CI = 1.01 - 3.76), IL-6 -572 G/C site (GG + GC vs CC: OR = 0.49, 95% CI = 0.29 - 0.84; GG vs CC + GC: OR = 0.76, 95% CI = 0.60 - 0.96; GG + CC vs GC: OR = 0.63, 95% CI = 0.49 - 0.81), IL-10 -819 T/C site (TT + TC vs CC: OR = 1.84, 95% CI = 1.01 - 3.34; T vs C: OR = 1.59, 95% CI = 1.00 - 2.51), and IL-10 -1 082 A/G site (AA + AG vs GG: OR = 0.77, 95% CI = 0.64 - 0.92; AA vs GG + AG: OR = 2.03, 95% CI = 1.16 - 3.58; A vs G: OR = 0.76, 95% CI = 0.61 - 0.94). The results of subgroup analysis showed that in Asian population, the loci associated with AITD were IL-6 -174 G/C site (GG vs CC + GC: OR = 4.61, 95% CI = 1.11 - 19.23; G vs C: OR = 0.65, 95% CI = 0.44 - 0.97); IL-6 -572 G/C site (GG vs CC + GC: OR = 0.64, 95% CI = 0.41 - 0.99; GG + CC vs GC: OR = 0.60, 95% CI = 0.38 - 0.94); IL-10 -819 T/C site (TT + TC vs CC: OR = 2.51, 95% CI = 1.48 - 4.25; T vs C: OR = 1.91, 95% CI = 1.05 - 3.46); and IL-10 -1 082 A/G site (AA + AG vs GG: OR = 0.66, 95% CI = 0.52 - 0.84; AA vs GG + AG: OR = 2.83, 95% CI = 1.54 - 5.21; A vs G: OR = 0.66, 95% CI = 0.53 - 0.82). Conclusion:IL-6 -174 G/C, IL-6 -572 G/C, IL-10 -819 T/C and IL-10 -1 082 A/G polymorphisms are associated with the susceptibility to AITD, especially in Asians.

Objective:To explore the clinical data of acute rejection in kidney transplant recipients of different ages with elderly donor kidneys.Methods:During January 2012 and June 2020, a retrospective review was conducted for clinical data of 298 recipients undergoing kidney transplantation from elderly donors aged ≥60 years after citizen's death.According to the age, recipients were divided into group A(age<30 yr, 59 cases), group B(30~39 yr, 125 cases), group C(40~49 yr, 83 cases)and group D(age≥50 yr, 31 cases). The incidence of acute rejection(AR)was analyzed.Also based upon age difference between donors and recipients, they were divided into two groups of(30~39 yr)and (40~49 yr)and the occurrence of AR was recorded.Results:The incidence of AR within 1 year post-transplantation in groups A, B, C, and D were 15.3%(9/59), 8.8%(11/125), 7.2%(6/83) and 3.2%(1/31)respectively.The incidence of AR in age difference≥25 yr group(12.5%)and age difference <25 yr group(5.3%) had significant difference( P<0.05). The proportion and absolute value of peripheral blood lymphocytes in each group at 1 week/month post-transplantation had significant difference( P<0.05). No significant difference was observed in serum level of creatinine(SCr), the incidence of pulmonary infection and urinary tract infection or the survival rate of recipients and transplanted kidneys in each group within 1 year post-transplantation among four groups( P>0.05). Conclusions:Elderly donor kidneys can obtain better transplant outcomes in kidney transplant recipients of different ages.As the age of recipients decreases, AR shows an upward trend.Clinicians should pay more attention to the prevention and treatment of AR in recipients with large age difference between donors and recipients.

OBJECTIVE:To observe the effectiveness and safety of different doses of rosuvastatin in the treatment of acute ce-rebral infarction. METHODS:Totally 120 patients with acute cerebral infarction were selected from Weifang Yidu Central Hospital during Jan. 2014-Dec. 2015,and then divided into observation group and control group according to admission order,with 60 cas-es in each group. Both groups received routine treatment as Shuxuening injection 10 mL,iv,1-2 times a day(or 20 mL added into 5% Glucose injection 250-500 mL,ivgtt,qd)+Aspirin enteric-coated tablets 0.1 g,po,qd. Control group and observation group were additionally given Rosuvastatin calcium tablets 10 mg and 20 mg,po,qd(after supper). Both groups were treated for 30 d. The levels of serum inflammatory factors(hs-CRP,TNF-α,IL-6),blood lipid indexes(TC,TG,LDL-C),neurological function and activity of daily life score were observed in 2 groups before and after treatment. The clinical efficacy and occurrence of ADR were recorded. RESULTS:Before treatment,there was no statistical significance in the levels of hs-CRP,TNF-α,IL-6,TC,TG and LDL-C,NIHSS scores and Barthel index (BI) scores between 2 groups (P>0.05). After treatment,the levels of hs-CRP, TNF-α,IL-6,TC,TG and LDL-C,NIHSS scores in 2 groups were decreased significantly,while BI scores were decreased signifi-cantly,observation group were significantly better than those of control group,with statistical significance (P<0.05). Total re-sponse rate of observation group (93.33%) was significantly higher than that of control group (86.67%),with statistical signifi-cance (P<0.05). The incidence of ADR in observation group (23.33%) was significantly higher than control group (6.67%), with statistical significance(P<0.05). CONCLUSIONS:Rosuvastatin can significantly reduce the inflammatory reaction and blood lipid level of patients with acute cerebral infarction,inhibit the formation of atherosclerotic plaque and improve prognosis. The large dose of rosuvastatin have better efficacy for acute cerebral infarction and can significantly improve the symptom of neurologi-cal deficits and daily living ability of patients.

Objective To investigate the effect of up-regulation of miR-132 on expressions of angiopoietin-1 (Ang-1)/endothelium-specific tyrosine kinase receptor 2 (Tie2) in focal cerebral ischemia reperfusion injury of rats.Methods Forty adult healthy SD rats were randomly divided into sham-operated group,cerebral ischemia group,miR-132 mimic group and negative control group (n=10).The models of middle cerebral artery occlusion in the later three groups were established by using modified Longa suture method.Rats in the miR-132 mimic group and negative control group were injected miR-132 mimic 15 μg and negative control 15 μg via paracele.Rats in each group were sacrificed 24 h after ischemia,and the brain tissues were collected;the total infarct volumes were calculated by TTC staining.The mRNA expressions ofmiR-132,Ang-1 and Tie2 in ischemic cerebral cortex tissues were detected by real-time fluorescence quantitative PCR.The protein expressions of Ang-1,Tie2,CD31 and vessel endothelial growth factor (VEGF) in ischemic cerebral cortex tissues were detected by Western blotting.Results The total infarct volume in the miR-132 mimic group was (27.92±3.05) mm3,which was significantly smaller than that in the cerebral ischemia group and negative control group ([51.34±2.86] mm3 and [50.46±2.57] mm3,P＜0.05).The relative mRNA expression levels of miR-132,A ng-1,Tie2,and the protein expression levels of Ang-1,Tie2,CD31,VEGF in the ischemic cerebral cortex tissues of the miR-132 mimic group were significantly higher than those in the negative control group,cerebral ischemia group and sham-operated group (P＜0.05);and those in the negative control group and cerebral ischemia group were significantly higher than those in the sham-operated group (P＜0.05).Conclusion Up-regulation ofmiR-132 expression could improve the ischemic states of ischemic stroke in rats,which might be related to Ang-1/Tie2 increased expressions to promote angiogenesis in ischemic brain tissues.