Diabetic kidney disease is one of the complications of diabetes,which can progress to end-stage renal disease.In recent years,it has been found that miRNAs have become a research hotspot,with miRNA-21 regulating transforming growth factor β1(TGF-β1)/Smads,phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT),Wnt/β-catenin and other signaling pathways to promote the progress of diabetic kidney disease.Studies have showed that traditional Chinese medicine has a regulatory effect on the expression of miRNA-21 and can target miRNA-21 to regulate TGF-β1/Smads,phosphatase and tensin homolog/PI3K/AKT/mammalian target of rapamycin(mTOR),peroxisome proliferator activated receptors and other signal transduction pathways to trigger signal cascade reactions,which intervene in pathological processes such as fibrosis,inflammation,oxidative stress and autophagy.In this article,the role of miRNA-21 in diabetic kidney disease and the intervention of traditional Chinese medicine were summarized,in order to provide some reference for the treatment of diabetic kidney disease and the development of new drugs.

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.
Male ; Mice ; Animals ; Cellular Reprogramming/genetics* ; Tetraploidy ; Pluripotent Stem Cells/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; DNA Methylation ; Spermatogonia/metabolism* ; Germ Cells/metabolism*

Objective:To investigate the predictors of early neurological deterioration (END) in patients with acute ischemic stroke (AIS) based on the Oxfordshire Community Stroke Project (OCSP) classification system.Methods:Patients with AIS admitted to the Department of Neurology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from February 2018 to November 2020 were enrolled retrospectively. According to the OCSP criteria, the patients were classified into total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), posterior circulation infarct (POCI), and lacunar infarct (LACI). END was defined as the National Institutes of Health Stroke Scale (NIHSS) total score within 72 h after onset increased by ≥2 or motor function score increased by ≥1 compared with the baseline. Multivariate logistic regression analysis was used to determine the independent risk factors for END in AIS patients with different OCSP types. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of each index for END in AIS patients with different OCSP types. Results:A total of 405 patients with AIS were enrolled. Their age was 68.84±12.27 years, and 250 were males (61.7%); 132 patients (32.6%) were in the TACI group, 108 (26.7%) were in the PACI group, 61 (15.1%) were in the POCI group, and 104 (25.7%) were in the LACI group. END occurred in 136 patients (33.6%). Multivariate logistic regression analysis showed that homocysteine (Hcy) (odds ratio [ OR] 1.065, 95% confidence interval [ CI] 1.012-1.212; P=0.015), baseline NIHSS score ( OR 1.209, 95% CI 1.095-1.335; P<0.001) and the time from onset to admission ( OR 1.663, 95% CI 1.282-2.082; P<0.001) were significantly and independently correlated with END in the TACI group. Hcy ( OR 1.137, 95% CI 1.040-1.244; P=0.005), fasting blood glucose ( OR 1.714, 95% CI 1.272-2.311; P<0.001), neutrophil to lymphocyte ratio (NLR) ( OR 1.370, 95% CI 1.016-1.848; P=0.039) and the time from onset to admission ( OR 1.266, 95% CI 1.056-1.519; P=0.011) were significantly and independently correlated with END in the PACI group. NLR ( OR 1.446, 95% CI 1.031-2.027; P=0.033) was significantly and independently correlated with END in the POCI group. Fasting blood glucose ( OR 1.301, 95% CI 1.006-1.683; P=0.045), NLR ( OR 1.393, 95% CI 1.025-1.894; P=0.034) and the time from onset to admission ( OR 1.171, 95% CI 1.008-1.361; P=0.039) were significantly and independently correlated with END in the LACI group. ROC curve analysis showed that the areas under the curve (AUC) of Hcy and baseline NIHSS score for predicting END in the TACI group were 0.617 (95% CI 0.521-0.713; P=0.021) and 0.784 (95% CI 0.706-0.862; P<0.001). The optimal cut-off values were 15.91 μmol/L and 19.5 points, respectively. The sensitivity and specificity were 63.7% and 85.2%, 62.0% and 86.9%, respectively. The AUC of Hcy, fasting blood glucose and NLR for predicting END in the PACI group were 0.672 (95% CI 0.548-0.797; P=0.005), 0.794 (95% CI 0.697-0.891; P<0.001) and 0.674 (95% CI 0.560-0.788; P=0.005), respectively. The optimal cut-off values were 15.2 μmol/L, 6.85 mmol/L, and 3.71, respectively. The sensitivity and specificity were 61.3% and 77.9%, 80.6% and 72.8%, 67.7% and 79.4%, respectively. The AUC of NLR for predicting END in the POCI group was 0.850 (95% CI 0.735-0.964; P<0.001). The optimal cut-off value was 5.2. The sensitivity and specificity were 84.2% and 81.4% respectively. The AUC of fasting blood glucose and NLR for predicting END in the LACI group were 0.728 (95% CI 0.614-0.842; P<0.001) and 0.731 (95% CI 0.614-0.842; P<0.001), respectively. The optimal cut-off values were 5.44 mmol/L and 2.71 respectively. The sensitivity and specificity were 80.0% and 62.7%, 76.0% and 79.2%, respectively. Conclusion:The predictors of END in AIS patients with different OCSP types are different.

Objective:To evaluate the utility of whole-exome sequencing (WES) in early diagnosis for children with language delay/disorder.Methods:Children with language delay/disorder who were admitted to the Department of Health Care, Children′s Hospital Affiliated to the Capital Pediatric Institute from January 2019 to December 2020 were analyzed retrospectively. Based on informed consent, the peripheral blood of the children and their parents was collected for WES. Combining the clinical phenotypes of the children, the candidate variants, including single nucleotide variants (SNVs) and copy number variations (CNVs), were selected for validation and family segregation analysis using Sanger sequencing, real-time PCR or CNV-Seq. The pathogenicity of variants was evaluated based on ACMG guideline following with finial genetic diagnosis. Based on whether genetic diagnosis was achieved or not, 125 children with comprehensive examination of the Children Neuropsychological and Behavioral Scale(CNBS-R2016) were sub-grouped (positive/negative group), and the total scores and the detailed scores of five developmental sections (gross motor, fine motor, adaptive ability, language and social behavior ability) between two subgroups were compared.Results:A total of 165 children with language delay/disorder were recruited, including 109 males and 56 females. The ratio of boys to girls was 1.95∶1.The age of the children was (3.2±1.2) years old, the median age was 3.0 years. 45 children carry disease-related pathogenic/likely pathogenic variants, including 36 SNVs and 9 CNVs. The genetic diagnostic yield of this cohort was 27.3% (45/165). The inheritance analysis for core family members showed de novo variant accounted for 86% of genetic diagnosis (31/36). The positive diagnosis rate in girls was 45% (25/56), which was significantly higher than that in boys (18.3%, 20/109, χ2=12.171, P<0.05). There was no significant difference in the rate of positive diagnosis among all age groups (χ2=4.349, P>0.05). Interestingly, the scores of gross motors of positive group were significantly lower than that of negative group (61.5 vs. 69.4, t=-2.610, P<0.05). Otherwise, no significant difference was seen between two groups( t=-0.933, -1.298, -0.114, -0.214, all P>0.05). Conclusions:Language delay/disorder has complex genetic heterogeneity. WES has important application value in early etiological diagnosis for children with language delay/disorder.

Objective:To evaluate the utility of whole-exome sequencing (WES) in early diagnosis for children with language delay/disorder.Methods:Children with language delay/disorder who were admitted to the Department of Health Care, Children′s Hospital Affiliated to the Capital Pediatric Institute from January 2019 to December 2020 were analyzed retrospectively. Based on informed consent, the peripheral blood of the children and their parents was collected for WES. Combining the clinical phenotypes of the children, the candidate variants, including single nucleotide variants (SNVs) and copy number variations (CNVs), were selected for validation and family segregation analysis using Sanger sequencing, real-time PCR or CNV-Seq. The pathogenicity of variants was evaluated based on ACMG guideline following with finial genetic diagnosis. Based on whether genetic diagnosis was achieved or not, 125 children with comprehensive examination of the Children Neuropsychological and Behavioral Scale(CNBS-R2016) were sub-grouped (positive/negative group), and the total scores and the detailed scores of five developmental sections (gross motor, fine motor, adaptive ability, language and social behavior ability) between two subgroups were compared.Results:A total of 165 children with language delay/disorder were recruited, including 109 males and 56 females. The ratio of boys to girls was 1.95∶1.The age of the children was (3.2±1.2) years old, the median age was 3.0 years. 45 children carry disease-related pathogenic/likely pathogenic variants, including 36 SNVs and 9 CNVs. The genetic diagnostic yield of this cohort was 27.3% (45/165). The inheritance analysis for core family members showed de novo variant accounted for 86% of genetic diagnosis (31/36). The positive diagnosis rate in girls was 45% (25/56), which was significantly higher than that in boys (18.3%, 20/109, χ2=12.171, P<0.05). There was no significant difference in the rate of positive diagnosis among all age groups (χ2=4.349, P>0.05). Interestingly, the scores of gross motors of positive group were significantly lower than that of negative group (61.5 vs. 69.4, t=-2.610, P<0.05). Otherwise, no significant difference was seen between two groups( t=-0.933, -1.298, -0.114, -0.214, all P>0.05). Conclusions:Language delay/disorder has complex genetic heterogeneity. WES has important application value in early etiological diagnosis for children with language delay/disorder.

Objective To study the clinical value of simultaneous amplification and testing for detection of Mycobacteria tuberculosis(SAT-TB)in sputum samples and bronchoalveolar lavage fluid(BALF)samples. Methods Totally 169 sputum samples and 151 BALF samples from suspected pulmonary tuberculosis patients were detected by both SAT and Bactec MGIT960.The sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)of the samples using SAT-TB were calculated. Results Taken the results of BD960 as the reference,the sensitivity,specificity,PPV and NPV using SAT-TB of sputum samples were 84.00% (42/50),93.06%(67/72),89.36%(42/47)and 89.33%(67/75)respectively;and those of BALF samples 89.19% (33/37),95.12%(39/41),94.29%(33/35)and 42.39%(39/92)respectively.Taken clinical diagnostic results as reference standard,the sensitivity,specificity,PPV and NPV using SAT-TB of the sputum samples were 57.73% (56/97),93.06%(67/72),91.80%(56/61),and 62.04%(67/108)respectively;and those of BALF samples 51.82%(57/110),94.29%(39/41),96.61%(57/59)and、42.39%(39/92)respectively.The sensitivity,specificity, PPV and NPV using BD960 of the sputum samples were 51.55%(50/97),95.83%(69/72),94.34%(50/53),and 59.48%(69/116)respectively;and those of BALF samples 33.64%(37/110),90.24%(37/41),90.24%(37/41) and 33.64%(37/110)respectively.Conclusion SAT-TB is a rapid and sensitive method for the detection of Myco-bacteria tuberculosis in sputum and BALF samples.It can improve the detection rate of mycobaterium tuberculosis.

Objective To analyze the influences of maternal high-fat diet on male rat offspring's blood lipid level and hepatic lipid deposition as well as on the expression of two key factors,sterol regulatory element binding protein-1 (SREBP-1) and SREBP cleavage acting protein (SCAP),involved in hepatic cholesterol regulatory cascade during childhood and adulthood.Methods Pregnant Wistar rats were randomly divided into two groups:high fat diet (HF) group and normal intake control (NC) group (both n=20).Rats in the HF group were fed with high-fat diet till delivery before changing to a normal-fat diet,while the NC group was given the normal-fat diet all through the study.Male offspring born appropriate for gestational age (AGA) in different feeding groups were randomly selected as experimental subjects.Physical development,serum lipid levels and hepatic lipid deposition at the age of 7 and 24 weeks were compared between offspring of the two groups.Expression of SCAP and SREBP-1 at protein level was detected with immunohistochemistry.T test or Chi-square test was used for statistical analysis.Results The average birth weight of HF group was higher than that of NC group [(6.95± 0.25) vs (6.79 ±0.78) g,t=2.088,P=0.038].Large for gestational age (LGA),AGA and small for gestational age (SGA) offspring accounted for 18.6％ (21/113),77.9％ (88/113)and 3.5％ (4/113) in HF group and 7.6％ (10/132),87.9％ (116/132) and 4.5％ (6/132) in NC group (x2=13.500,P=0.001).At the age of 7 weeks,the offspring's body weight in HF group was higher than that in NC group [(68.78±7.55) vs (66.61 ±3.92) g,t=2.303,P=0.023].At the age of 24 weeks,the body weight,body length and abdominal circumference of adult offspring in HF group were significantly higher than those in NC group [(251.74±24.04) vs (216.24±33.42) g,(22.60±0.79) vs (21.59± 1.34) cm,(17.93±0.59) vs (16.83±0.88) cm;t=2.220,2.379,2.927,all P＜0.05].At the age of 7 weeks,offspring's serum total cholesterol (TC) level in HF group was higher than that in NC group [(1.94±0.62) vs (1.23 +0.77) mmol/L,t=2.379,P＜0.05].At the age of 24 weeks,adult offspring's liver index,serum TC,triglyceride (TG),low density lipoprotein-cholesterol (LDL-C) and very low density lipoprotein-cholesterol (VLDL-C) levels were all higher in HF group than in NC group,while the high density lipoprotein-cholesterol (HDL-C) level was lower in HF group [(2.75±0.31)％ vs (2.46±0.39)％,(1.98±0.14) vs (1.45±0.27) mmol/L,(2.96±0.21) vs (2.71 ±0.29) mmol/L,(0.97±0.32) vs (0.71 ±0.21) mmol/L,(0.81 ±0.13) vs (0.52±0.17) mmol/L,(1.74±0.20) vs (1.59±0.29) mmol/L;t=2.264,2.333,2.359,2.088,5.336,1.994,all P＜0.05].Comparative analysis of nonalcoholic fatty liver disease activity scores (NAS) between the two groups showed that the liver lobular inflammation in HF group's offspring was more severe at both 7 and 24 weeks of age (2.29±0.49 vs 1.92±0.45,2.83±0.47 vs 2.22±0.55;t=2.157,3.251,all P＜0.05).At the age of 24 weeks,adult offspring in HF group also showed higher liver steatosis scores (2.81 ± 0.35 vs 2.25 ± 0.30,t=4.609,P＜0.05).Immunohistochemical detection showed that there was no significant difference in SCAP protein expressions in liver tissues of 7-week-old offspring between the two groups (P＞0.05),but higher expression of SREBP-1 protein was observed in HF group than in NC group [(34.16±5.08)％ vs (18.09±3.99)％,t=9.697,P＜0.05].At the age of 24 weeks,the expression levels of both SCAP and SREBP-1 proteins in liver tissues were higher in HF group than in NC group [(31.22±6.01)％ vs (17.98+7.89)％,(61.33± 16.25)％ vs (29.76± 11.21)％;t=2.303,2.274,both P＜0.05].Conclusions High-fat intake during pregnancy can increase offspring's birth weight and the risk for LGA offspring.Maternal high-fat diet even up-regulates the expression of SCAP and SREBP-1 in male offspring born AGA in childhood and this impact become more obvious when reaching adulthood,resulting in excessive increase of body weight,body length and abdominal circumference and elevated serum lipid level and liver lipid deposition.

The competence of scientific research ethnical review in domestic hospital was inadequate,which was associated with the development of medical ethnics,values of Chinese traditional society,unsound domestic laws and regulations,weak administrative management,unqualified committee of medical ethnics,the drive of scientific deriving interests and restriction of project funds.Aiming at the above problems,countermeasures were carried out to strengthen the construction of laws and regulations,strengthen the constraint of administrative management,standardize the self-construction of ethnic committee,implement the standard operative procedure,thus to provide a reference for the standardized construction of scientific research ethnical review.

In this paper , based on the analysis of the facing predicament of current situation of medical ethics education , the authors combined with the practice of medical ethics education and the school experience , based on the theory of life education , put forward to experience the activities of public medical treatment building practice of medical students medical ethics education system , promote the educational work to carry out the practice of medical colleges, improve the teaching quality of medical ethics education .

Objective: To provide a scientific standard of left ventricular Tei index for healthy people from various region of China, and to lay a reliable foundation for the evaluation of left ventricular diastolic and systolic function. Methods: The correlation and principal component analysis were used to explore the left ventricular Tei index, which based on the data of 3 562 samples from 50 regions of China by means of literature retrieval. hTe nine geographical factors were longitude(X1), latitude(X2), altitude(X3), annual sunshine hours (X4), the annual average temperature (X5), annual average relative humidity (X6), annual precipitation (X7), annual temperature range (X8) and annual average wind speed (X9). ArcGIS sotfware was applied to calculate the spatial distribution regularities of letf ventricular Tei index. Results: hTere is a signiifcant correlation between the healthy people’s letf ventricular Tei index and geographical factors, and the correlationcoeffcients were 0.107 (r1), 0.301 (r2), 0.029 (r3), 0.277 (r4),?0.256(r5),?0.289(r6),?0.320(r7), 0.310 (r8) and 0.117 (r9), respectively. A linear equation between the Tei index and the geographical factor was obtained by regression analysis based on the three extracting principal components. hTe geographical distribution tendency chart for healthy people’s letf Tei index was iftted out by the ArcGIS spatial interpolation analysis. Conclusion: hTe geographical distribution for letf ventricular Tei index in China follows certain pattern. hTe reference value in North is higher than that in South, while the value in East is higher than that in West.