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 To observe the impact of ultrasonic image quality on the consistency of artificial intelligence(Al)assisted diagnosis system and manual measurements of biological indicators of developmental dysplasia of hip(DDH).Methods Hip ultrasonic data of 75 DDH and 345 non-DDH children were retrospectively analyzed,and the quality of ultrasonic images were subjectively scored.An evaluation model of ultrasonic image quality was constructed based on 140 ultrasonic images acquired from 140 cases(group A,containing 25 DDH and 115 non-DDH)using entropy weighting method,the weight of anatomic structures and impact factors related to DDH were obtained.The comprehensive image quality scores of other ultrasonic images acquired from 280 cases(group B,including 50 DDH and 230 non-DDH)were calculated,and the images in group B were classified into grade A,B and C in descending order.The consistency of AI and manual measurements of DDH biological indicators in group B was assessed.Results The weight of each anatomic structure and impact factors of DDH obtained with the model were as follows:The lower edge of iliac branch＞ilium＞glenoid labrum＞bony margin＞femoral head＞motion artifacts.In group B,grade A was observed in 67(9 DDH and 58 non-DDH),grade B was found in 160(26 DDH and 134 non-DDH),while grade C was noticed in 53(15 DDH and 38 non DDH)images.Except for β,femoral head coverage(FHC)and femoral head length diameter,the consistencies between AI and manual measurements of other indicators of DDH were grade A＞B＞C.In group B,AI and manual measurements were more consistent in DDH than in non-DDH cases.Conclusion Ultrasonic image quality affected the consistency between AI and manual measurements of biological indicators of DDH.When image quality was not good enough,further attention should be paid to measurement of FHC and sizes of femoral head.

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 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 analysis the change of hip joint in healthy infants by ultrasound,and establish the normal reference value of the developmental dysplasia of the hip(DDH). Methods A total of 8 000 healthy infants from 0 to 24 weeks were collected from the Multi-center study of 10 children′s medical centers. Among them,3 855 infants(2 065 females and 1 790 males) with complete data and follow-up were included in this study. All subjects were divided into 6 groups ( ＜4,4～7,8～11,12～15,16～19 and≥20 weeks group). α angle,femoral head length and width,femoral head coverage ratio by acetabulum ( FHC) were measured in the coronal view on the neutral position;distance from pubis to femoral head ( P-H) and distance from ischium to femoral head ( I-H ) were measured in the transverse view on neutral position;distance from femoral head topubis ( H-P) was measured in the posterolateraltransverse view on the flexion position. The results of each group changes with age were analysised. Results ① The α angle of healthy infants from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05),but there was no significant difference between 16～19 and ≥20 weeks group( P ＞0.05). ②The femoral head length and width of all age groups were increased with age,the difference among all the groups was statistically significant( all P ＜0.05). ③ FHC from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05) except between 16～19 and ≥20 weeks group( P ＞0.05). ④ The P-H and I-H in all age groups showed no statistically significant ( all P＞0.05). ⑤The H-P of all age groups were increased with age,the difference between the groups were statistically significant(all P ＜0.05).Conclusions The development of hip joints have the certain regular developmental pattern in healthy infants less than 5 months of birth and are relatively constant after birth more than 5 months. The ultrasound normal reference value of the hip joints can be used for the early diagnosis of the DDH.

AIM:To investigate the effect of rhein on bleomycin-induced pulmonary fibrosis and the expression of microRNA-21 (miR-21) and transforming growth factor-β1 (TGF-β1)/Smad signaling molecules in rats.METHODS:A single dose of bleomycin was intratracheal injected into the SD rats to induce pulmonary fibrosis .After injection of bleo-mycin, the rats were randomly divided into low-, medium-and high-dose rhein treatment groups and model group .The rats that were instilled with normal saline intratracheally served as control group .After the treatment for 28 d, the pulmonary pathologic changes were observed under microscope with hematoxylin-eosin staining .The lung coefficient and hydroxypro-line content were also measured .The expression of miR-21 and the mRNA levels of TGF-β1 and Smad7 in the lung tissues were detected by real-time PCR.The protein levels of TGF-β1 and Smad7 were determined by Western blot .RESULTS:Rhein significantly attenuated the experimental alveolitis , pulmonary fibrosis , lung coefficient and hydroxyproline contents in the rats.Rhein obviously decreased the expression of miR-21,and the mRNA and protein levels of TGF-β1, but signifi-cantly increased the mRNA and protein levels of Smad 7 in the lung tissues .CONCLUSION: Rhein effectively prevents bleomycin-induced pulmonary fibrosis by inhibiting the expression of miR-21 and promoting the expression of Smad 7, thus regulating the TGF/Smad signaling pathway to decrease extracellular matrix deposition .

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.

Objective To detect the expression change of ETFβin diabetic nephropathy rats and study the role of ETFβin fatty acid-induced apoptosis in renal tubules.Methods Diabetic nephropathy model was established by intraperitoneal injection of streptozotocin and unilateral nephrectomy.In vivo ETFβexpression was detected in renal cortex, as well as tubular injury evaluated.In vitro fatty acid-induced apoptosis in renal tubular cells NRK 52E model was established and ETFβrecombinant plasmid was constructed to be transfected into NRK 52E cells and furtherly to observe the effect of ETFβover-expression on the fatty acid-induced apoptosis.Results In the rats model of diabetic nephropathy induced by streptozotocin injection and unilateral nephrectomy, ETFβmRNA and protein expression were decreased as obvious tubular damage occurred.Fatty acids could induce apoptosis in NRK 52E, and ETFβover-expression reduced the apoptosis.Conclusion The expression of ETFβis decreased in diabetic nephropathy model , and ETFβover-expression can reduce apoptosis induced by fatty acid in renal tubular cells.