Objective To investigate the dynamic expressions of exchange protein directly activated by cyclic adenosine monophosphate (cAMP) (Epac) in rat model of hepatic fibrosis(HF).Methods Forty-two male SD rats were divided into control group (n = 6) and model group (n = 36)which was divided into six subgroups of day 4, week 1, week 2, week 4,week 6 and week 8 with six rats in each subgroup. The rat model of HF was established by intraperitoneal injection of dimethylnitrosamine (DMN). The pathological changes of liver were observed by Hematoxylin-Eosin and Masson staining. Reverse transcription-polymerase chain reaction (RT-PCR),immunohistochemistry and Western blot were employed to detect the mRNA and protein expressions of Epac1, Epac2 and transforming gronth factor (TGF)β1 during the process of modeling and localization in the liver. The statistical analysis was done using one-factor ANOVA, LSD-t test,Dunnett T3 test and Pearson linear correlation analysis. Results Rat model of liver fibrosis was established successfully. In control group, Epac1 (0. 031 28±0. 008 96) and Epac2 protein (0.034 43±0. 002 45) mainly expressed in the cytoplasm of hepatocytes. In model group, the level of Epac1 decreased at day 4 (0. 023 97±0. 003 81) and week 1 (0. 015 81±0. 002 48) ,then began to increase at week 2 of modeling and peaked at week 6 (0. 039 54±0. 001 43), which had statistical significance compared to the control group (t= 5.47,11.58 and - 6.18, respectively; all P＜0.05). Epac2 protein expression declined after modeling, reached the lowest level at week 4 (0. 011 21 ±0. 001 32), which had statistical significance compared to the control group (t= 24. 50, P＜0. 05). TGFβ1 protein expression increased after modeling and peaked at week 4 (0. 011 30±0.001 03) which had statistical significance (t= -23. 36, P＜0. 05) compared to the control group (0. 002 08 ±0. 000 18). The expressions of Epac1, Epac2 and TGFβ1 mRNA were consistent with the trend of protein levels.Correlation analysis showed that Epac1 protein was positively correlated with the course of HF (r =0. 703, P＜0.01 ), while Epac2 protein was negatively correlated (r = - 0. 409, P＜0.05). Conclusions During the progression of HF, Epac1 expression tends to decrease firstly and increase afterwards,while Epac2 expression declines continually. Epac may be involved in the pathogenesis of HF.

Objective To investigate the changes and clinical significance of the frequency of circulating CD4+ CD25+ regulatory T cells (Treg) in nonalcoholic fatty liver (NAFL) patients.Methods CD4+ CD25+ Treg in the peripheral blood from 50 NAFL patients and 50 healthy subjects were quantitatively analyzed using flow cytometry. Group t test or Mann-Whitney U test and Spearman's rank correlation test were used for statistical analysis.Results The proportion of circulating CD4+CD25+ Treg in NAFL patients was (5.39 ± 1.94)％,which was significantly higher than that in healthy controls [(4.21±1.52)％](t=3.385,P＜0.01).Further analysis revealed that the frequency of Treg was positively correlated with triglyceride (TG) level and body mass index (r=0.307 and 0.251,respectively; P=0.002 and 0.012,respectively),and negatively correlated with high density lipoproteincholesterol (HDL-C) (r=-0.306,P=0.002).Meanwhile,Treg in patients with high body mass index,high TG,low HDL-C,hypertension and metabolic syndrome (MS) were all higher than those in controls (t=2.294,2.533,3.154,2.010 and 4.454,respectively; all P＜0.05).But there was no significant difference between patients with high fasting blood glucose and controls (U=1143.500,P=0.471).Conclusion The increased frequency of peripheral Treg in NAFL patients may have some relations with the imbalance of proinflammation and anti-inflammation in NAFL patients who coexisting with MS.

Objective:To explore the clinical effect of mycophenolate mofetil combined with glucocorticosteroid on the children with anaphylatic purpura nephritis.Methods:70 cases of children treated and diagnosed as anaphylatic purpura nephritis in our hospital from March,2012 to September,2015 were enrolled in this study.They were randomly divided into the observation group and the control group.Conventional therapy was applied to both groups,the observation group was treated by mycophenolate mofetil combined with prednisone,the control group was given cyclophosphamide combined with prednisone.The total effective rate,disappearence time of clinical symptoms,biochemical indicators,immune function as well as the incidence of adverse reactions were compared between the two groups.Results:The total effective rate of observation group was 94.29％,which was 85.17％ in the control group,no statistical difference was found between two groups(P＞0.05).After therapy,the disappearence time of albuminuria,hematuria in observation group showed no significant difference compared with those of the control group,the level of 24 h urine protein quantitation and CD19+ of both groups were significantly decreased,and the level of CD19+ of observation group was significantly lower than that of the control group (P ＜0.05),the level of albumin,total protein and CD3+,CD3+CD4+ of both groups were significantly increased,and the level of CD3+,CD3+CD4+of observation group were significantly higher than those of the control group (P＜0.05).The incidence of adverse reactions in observation group was significantly lower than that of the control group (P ＜0.05).Conclusion:Mycophenolate mofetil combined with glucocorticosteroid was more effective and safe on the children with anaphylatic purpura nephritis than that of cyclophosphamide combined with prednisone.

As the population ages worldwide,dementia patients increase at a high rate of 7.7 million each year,which has a huge impact on quality of life of the elder.It is not surprising,therefore,that early detection of individuals at high risk for dementia and the development of effective interventions are major public health priorities.There is increasing evidence that gait slowing occurs early in the course of dementia,precedes declines in cognitive tests,and is a strong predictor of dementia.Hence,incorporating gait performance into risk assessments is a novel and simple approach that can help improve dementia prediction.The motoric cognitive risk syndrome (MCR) is a predementia syndrome characterized by the presence of cognitive complaints and slow gait in older individuals without dementia or mobility disability.In addition,studies have shown MCR as a predictor of other negative outcomes in older adults,including disability,falls and death.However,the concept of MCR is still in its early stage and approach to the syndrome is not yet well established in China.This review aims to demonstrate the various aspects of MCR syndrome including its pathophysiology,diagnosis,epidemiology,and relationship with other geriatric conditions.

The cases of paradoxical brain embolism (PBE) due to venous aneurysms and patent foramen ovale (PFO) are extremely scarce, with only 5 cases caused by popliteal venous aneurysm reported in the literature to date, while PBE caused by deep femoral venous aneurysm (DFVA) and PFO has not been reported. Herein, an unusual case of PBE in a 15-year-old girl with PFO who still had cerebral infarction and pulmonary embolism after transcatheter closure was present. She was finally diagnosed as PFO with DFVA by angiography. Furthermore, clinical characteristics of 6 cases were summarized to improve the clinicians′ recognition of the rare risk factor of stroke-venous aneurysms of the lower extremity deep veins.

Objective:To analyze the gene mutation, clinical manifestations and prognosis of children with steroid resistant nephrotic syndrome (SRNS), and to provide reference for the treatment of hereditary SRNS in children.Methods:The clinical data of 29 patients with SRNS and whole exon sequencing (WES) diagnosed in Xi′an Children′s Hospital from January 1, 2018 to December 31, 2020 were retrospectively analyzed.Results:In 29 cases of SRNS with genetic testing, 10 cases (34.5%) were gene mutations, including 2 cases of congenital nephrotic syndrome. The onset age of the patients with gene mutation ranged from 0.1 to 10.7(4.06±3.73)years, and the median age of onset was 3.3 years. The clinical type was mainly nephritis (8/10), and the pathological type was mainly focal segmental glomerulosclerosis (FSGS) (5/7). The main mutant genes were NPHS1 (2 cases), NPHS2 (2 cases), WT1 (2 cases), SMARCAL1 (1 case), COQ8B (1 case), TRPC6 (1 case) and COL4A3 gene (1 case). The main types of genetic variation were missense mutations, and 6 (60%) cases were new mutations that had never been reported in the database containing human pathogenic mutations before. Compared with the non-gene mutation group, 24 hour urinary protein was higher [(177.92±164.59)mg/(kg·24 h) vs (84.99±40.79)mg/(kg·24 h)] in gene mutation group, with statistically significant difference ( P<0.05). In the gene mutation group, there were 2 cases of complete remission, including 1 case of complete remission treated with coenzyme Q10, 1 case of partial remission, and 8 cases of immunosuppression treatment, with an effective rate of 2/8, while in the non-gene mutation group, the effective rate of immunosuppression treatment was 17/19, with statistically significant difference in prognosis between the two groups ( P<0.05). Conclusions:The pathological type of children with hereditary SRNS is mainly FSGS, which are often ineffective to immunosuppressive therapy, poor prognosis and easy to progress to end-stage renal disease. Gene detection is of great significance for etiological diagnosis, treatment and prognosis evaluation in children with SRNS.

The somatic cells can be induced into ES-like stem cells when retrovirally infected the defined transcription factors including Oct4, Sox2, Klf4 and c-Myc. These ES-like cells are named induced pluripotent stem (iPS) cells and this method is called iPS technology. Until the end of 2009, iPS cell lines have been generated in various animal species, such as mouse, human, rhesus monkey, rat and pig. Mouse iPS cells are also used to generate chimera mice and viable mice through the tetraploid complementation. Although iPS cells are extremely similar to ES cells in both morphology and growth features, to generate iPS cells do need the defined culture procedures. Based on the update global iPS technology development and the iPS studies in our laboratory, this paper focused on the establishment of iPS cell lines and improvement of iPS cell culture condition.
Animals ; Cell Culture Techniques ; methods ; Cell Differentiation ; Embryonic Stem Cells ; cytology ; metabolism ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Kruppel-Like Transcription Factors ; genetics ; metabolism ; Octamer Transcription Factor-3 ; genetics ; metabolism ; Proto-Oncogene Proteins c-myc ; genetics ; metabolism ; SOXB1 Transcription Factors ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism

0bjective To analyze the clinical characteristics, pathological types, treatment and prognosis in children with steroid resistant nephrotic syndrome (SRNS) in Northwest China, in order to provide reference for the treatment of SRNS. Methods:The clinical data, renal pathological results, treatment plan and efficacy of 102 children diagnosed with SRNS in the Department of Nephrology, Xi'an Children's Hospital of Shaanxi Province from January 1st, 2018 to December thirty-first, 2020 were analyzed retrospectively. All children were divided into groups according to age, clinical classification, pathological type, treatment scheme and treatment outcome, and the risk factors affecting the prognosis of children with SRNS were discussed. The measurement datas conforming to normal distribution were expressed as xˉ± s, and t test was used for comparison between groups. Measurement datas that did not conform to normal distribution were represented by M ( Q1, Q3), and Kruskall-Wallis test was used for comparison between groups.Enumeration datas were compared by χ 2 test. Risk factors were analyzed by multiple factor Logistic regression analysis. Results:The median age of onset of 102 children with SRNS was 3.0 years. Focal segmental glomerulosclerosis (FSGS) accounted for 36.3% (37/102), minimal lesions accounted for 33.3% (34/102), and mesangial proliferative glomerulonephritis accounted for 23.5% (24/102). The prevalence rates of hypertension (35.1% (13/37)), 24-h urine protein quantification (130.5 (91.5, 159.6) mg/(kg·24 h) and renal insufficiency (21.6% (8/37)) in FSGS group were higher than those in non-FSGS group (13.8% (9/65), 65.8 (51.2,85.5) mg/(kg·24 h), 4.6% (3/65)). The differences between the two groups were statistically significant (statistical values were χ 2=6.32, Z=5.90, χ 2=7.09; P values were 0.012, <0.001, 0.008). Logistic multivariate regression analysis showed that the hypertension ( OR=4.055, 95% CI 1.178-3.962) and 24 hour urinary protein ( OR=1.036, 95% CI 1.020-1.053) were associated with the increased risk of FSGS ( P values were 0.026 and <0.001). ROC curve ananlysis showed that the optimal critical value of 24 hour urinary protein was 85.65 mg/(kg·24 h) in FSGS. After treatment, complete remission was 61.8%(63/102), partial remission was 14.7%(15/102), and no remission was 23.5%(24/102). By the end of follow-up the treatment effective rate in the small lesion group (94.1%(32/34)) was higher than that in the FSGS Group (51.3%(19/37)), and the difference between the two groups was statistically significant (χ 2=16.02, P<0.001). In the initial immunosuppressive treatment, the complete remission rate of hormone combined with calcineurin inhibitor group (77.1%(37/48)) was higher than that of hormone combined with cyclophosphamide Group (11.1%(3/27)). There was significant difference between the two groups ( Z=32.28, P<0.001). Conclusion:The most common pathological type in children with SRNS was FSGS, and the age of onset was generally small. The prognosis of patients with pathological type FSGS was the worst, and the prognosis of small lesions was better. Hypertension and 24-hour urinary protein quantification were the risk factors of FSGS. Calcineurin inhibitors were the first choice for the second-line immunosuppressants of SRNS in children.

Objective:To analyze the level of homocysteine (HCY) and its influencing factors in different ethnic groups in Lhasa, and to explore its reference interval.Methods:Reference interval study. The serum HCY (μmol/L) level of 820 healthy subjects was analyzed in Tibet autonomous region People′s hospital from January to December 2018. All the subjects were divided into groups according to ethnicity, gender, age and season. The general linear model was used to analyze the differences in serum HCY levels groups. According to the CLSI C28 document, the Nested ANOVA and Z test were used to analyze and determine whether or not different groups need to establish the reference interval. Results:Ethnicity, age and gender had significant effects on serum HCY. The level of HCY in Tibetan was higher than that in Han (P<0.001); the level of Hcy in male was higher than that in female ( P<0.001); the level of HCY in over-50 year old group was higher than that in under-50 year old group ( P=0.01). There was no significant difference in serum HCY level in seasonal distribution ( P=0.22). Nested ANOVA and Z tests confirmed that the HCY reference interval in Lhasa should be established according to ethnicity and gender in clinical application. The reference interval of HCY level in Lhasa area was established according to difference genders, including<22.41 μmol/L for Tibetan men,<18.41 μmol/L for Tibetan women. Conclusions:The serum HCY levels of the apparent healthy people in Lhasa area were slightly different among people of different ethnicities, genders and ages. We established the reference intervals of HCY of different ethnic groups and gender groups in Tibet and our results have practical significance for the prevention and treatment of cardiovascular and cerebrovascular diseases at high altitude.

OBJECTIVETo investigate the etiology of severe hand-foot-mouth disease (HFMD) in children in Henan province.

METHODSA total of 244 HFMD cases admitted to a hospital in Zhengzhou from April to June of 2014 were recruited for research sampling, Real-time RT-PCR, virus isolation, VP1 sequencing and alignment methods were used to test the enterovirus-related etiology. SPSS 17.0 was used in performing statistical analysis.

RESULTSThere were 109 severe and 135 mild cases among all the 244 HFMD cases. The number of enterovirus positive stool samples was 229, with positive rate as 93.85%. EV71, Cox A16 and Cox A10 made up 83.84%, 5.68% and 8.30% of the enterovirus etiologicy, strains, respectively. EV71 infection caused 8 HFMD cases with heart-lung failure and 2 death, Cox A10 infection led to 1 HFMD case with heart-lung failure and death. There were statistically differences seen regarding the enterovirus infection rates between severe and the mild HFMD cases (χ(2)=5.312,P=0.021). Statistically significant difference was seen in the constituent ratio of EV71, Cox A16 and the others by Fisher' s exact test (P=0.048). There was statistically significant difference seen between the cardiorespiratory failure rate and the fatality rate by EV71 and Cox A10 infection (χ(2)=0.051,P=0.821; χ(2)=2.198,P=0.138). Cox A10 strains idenfied in Henan in 2014 belonged to genotype 6. The rates on homology of nucleotide and amino acid among the Cox A10 strains in Henan in 2014 were 94.3%-99.7% and 96.3%-100.0% respectively.

CONCLUSIONSEV71 still remained the most common pathogen that causing severe HFMD in children, with the increasing Cox A10 percentage in the pathogens spectrum of HFMD infection. Cox A10 strains in Henan in 2014 belonged to genotype 6. Genotype 6 Cox A10 had appeared and widely distributed in Henan for long time, but not yet variated or reconstructed. Cox A10 infection could lead to cardio-respiratory failure thus called for the monitoring program on non-EV71 and non-Cox A16 enterovirus, especially Cox A10 to be strenthened.

Amino Acids ; genetics ; Biometry ; Child ; Enterovirus A, Human ; classification ; genetics ; isolation & purification ; Enterovirus Infections ; epidemiology ; virology ; Evolution, Molecular ; Genotype ; Hand, Foot and Mouth Disease ; epidemiology ; prevention & control ; virology ; Hospitals ; statistics & numerical data ; Humans ; Real-Time Polymerase Chain Reaction