To investigate the correlation of polymorphisms at the rs1837253 and rs3806933 loci of the thymic stromal lymphopoietin(TSLP)gene with asthma susceptibility and Eos,IgE,and FeNO levels in children.A total of 143 asthmatic children were selected as the study group,and 112 healthy children undergoing routine health examinations at the same hospital were chosen as the control group.The MassARRAY SNP genotyping technology was used to detect the genotypes at two loci,while serum IgE levels were determined by using the turbidimetric scattering method.The distribution differences in genotype and allele frequencies between the two groups were analyzed,along with the effects of different genotypes on Eos,IgE,and FeNO levels.There was no statistically significant difference in the distribution of rs1837253 allele and genotype frequencies as well as rs3806933 allele frequencies between the two groups(P＞0.05).However,asthma group rs3806933 CT genotype frequency was higher than the control group,and CC genotype frequency was lower than the control group(P＜0.05).Compared with the wild-type genotypes,children who carried rs1837253 CT+CC and rs3806933 CT,CT+TT genotypes had an increased risk of asthma(CT+CC vs TT:OR=2.737,95%CI:1.514-4.945;CT vs CC:OR=2.058,95%CI:1.194-3.543;CT+TT vs CC:OR=1.843,95%CI:1.109-3.062).There was an overall statistical difference in Eos counts among the three genotypes at the rs1837253 locus in the asthma group(P＜0.05,correction for multiple comparisons P＞0.05),but not in the control group(P＞0.05).There were no statistically significant differences in Eos%,IgE,and FeNO levels among the genotypes at the two loci and no significant difference in Eos counts among genotypes at the rs3806933 loci(P＞0.05).Taken together,polymorphisms at rs1837253 and rs3806933 loci in the promoter region of the TSLP gene are associated with asthma susceptibility in children.rs3806933 CT genotype may serve as a potential genetic marker for asthma,and rs1837253 CT+CC and rs3806933 CT+TT genotypes are risk factors for asthma in children;the rs1837253 locus polymorphism tended to affect blood Eos counts,while the two SNPs were not associated with Eos%,serum IgE,and FeNO levels.

Objective To investigate the expression and clinical value of γδT cells and related inflammatory factors in endometrial polyps(EP).Methods Subjects were patients with infertility due to EP(EP group,n=57)and infertility due to non-uterine factors(Control group,n=44).EP tissues and normal endometrial tissues were taken,respectively.The general characteristics of the two groups were evaluated by independent samples T-test or Wilcoxon rank sum test.The expressions of CD3 and TCRγδ in proliferative endometrium and endometrial polyps were observed by immunofluorescence,and the expressions of IL-17 and IFN-γ in tissue homogenate were detected by ELISA.Uni-variable linear regression was used to analyze the correlation between the number of γδT cells and the expression level of IL-17 and IFN-γ.Results Both the number of γδT cells and he levels of IL-17 and IFN-γsignificantly increased in endometrial polyp tissues,and the relationship between is linear(all P＜0.05).Conclu-sion γδT cells are associated with EP among infertile women,which may lead to embryo implantation failure by affecting the expression of inflammatory factors and regulating the imbalance of cell subsets.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective To observe the therapeutic effect of probiotics combined with montelukast in children with Mycoplasma pneumoniae pneumonia(MPP)complicated with myocardial injury.Methods A total of 102 children with MPP and myocardial injury were selected as the study objects,and were randomly divided into control group and observation group,with 51 cases in each group.The control group was treated with montelukast,and the observation group was treated with probiotics based on the control group.The clinical efficacy,symptom resolution time,hospital stay,myocardial injury index,inflammatory cytokines,intestinal flora level and incidence of adverse reactions were compared between the two groups.Results The total effective rate of the observation group was 92.16％,which was significantly higher than 76.47％of the control group(P＜0.05).The disappearance time of symptoms of fever,cough,shortness of breath,chest tightness and chest pain and hospital stay in the observation group were significantly shorter than those in the control group(P＜0.05).After treat-ment,the levels of cardiac troponin T(cTnT),B-type natriuretic peptide(BNP),myoglobin(Mb)and cardiac fatty acid binding protein(H-FABP)in the observation group were significantly lower than those in the control group(P＜0.05);the levels of interleukin-1 receptor 1(IL-1R1),gamma-interferon(γ-IFN)and high mobility group protein 1(HMGB1)in the observation group were significantly lower than those inthe control group(P＜0.05);the number of Bifidobacteria,Lactobacillus aci-dophilus,Enterococcus faecalis and Bacillus cereus in the observation group were significantly higher than the control group,while the number of Escherichia coli and Salmonella were significantly lower than those in the control group(P＜0.05).There was no significant difference in the incidence of ad-verse reactions between the two groups(P＞0.05).Conclusion Probiotics combined with monte-lukast have good efficacy in MPP children with myocardial injury,which can shorten the time of symp-tom resolution and hospital stay,improve the indexes of myocardial injury in children,inhibit the lev-el of inflammatory cytokines,adjust the structure of intestinal flora disorder,and have good safety.

Our recent studies for nonnucleoside reverse transcriptase inhibitors identified a highly potent compound JK-4b against WT HIV-1 (EC₅₀ = 1.0 nmol/L), but the poor metabolic stability in human liver microsomes (t _1/2 = 14.6 min) and insufficient selectivity (SI = 2059) with high cytotoxicity (CC₅₀ = 2.08 μmol/L) remained major issues associated with JK-4b. The present efforts were devoted to the introduction of fluorine into the biphenyl ring of JK-4b, leading to the discovery of a novel series of fluorine-substituted NH₂-biphenyl-diarylpyrimidines with noticeable inhibitory activity toward WT HIV-1 strain (EC₅₀ = 1.8-349 nmol/L). The best compound 5t in this collection (EC₅₀ = 1.8 nmol/L, CC₅₀ = 117 μmol/L) was 32-fold in selectivity (SI = 66,443) compared to JK-4b and showed remarkable potency toward clinically multiple mutant strains, such as L100I, K103N, E138K, and Y181C. The metabolic stability of 5t was also significantly improved (t _1/2 = 74.52 min), approximately 5-fold higher than JK-4b in human liver microsomes (t _1/2 = 14.6 min). Also, 5t possessed good stability in both human and monkey plasma. No significant in vitro inhibition effect toward CYP enzyme and hERG was observed. The single-dose acute toxicity test did not induce mice death or obvious pathological damage. These findings pave the way for further development of 5t as a drug candidate.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Brain development requires a delicate balance between self-renewal and differentiation in neural stem cells (NSC), which rely on the precise regulation of gene expression. Ten-eleven translocation 2 (TET2) modulates gene expression by the hydroxymethylation of 5-methylcytosine in DNA as an important epigenetic factor and participates in the neuronal differentiation. Yet, the regulation of TET2 in the process of neuronal differentiation remains unknown. Here, the protein level of TET2 was reduced by the ubiquitin-proteasome pathway during NSC differentiation, in contrast to mRNA level. We identified that TET2 physically interacts with the core subunits of the glucose-induced degradation-deficient (GID) ubiquitin ligase complex, an evolutionarily conserved ubiquitin ligase complex and is ubiquitinated by itself. The protein levels of GID complex subunits increased reciprocally with TET2 level upon NSC differentiation. The silencing of the core subunits of the GID complex, including WDR26 and ARMC8, attenuated the ubiquitination and degradation of TET2, increased the global 5-hydroxymethylcytosine levels, and promoted the differentiation of the NSC. TET2 level increased in the brain of the Wdr26^+/- mice. Our results illustrated that the GID complex negatively regulates TET2 protein stability, further modulates NSC differentiation, and represents a novel regulatory mechanism involved in brain development.
Animals ; Mice ; DNA-Binding Proteins/genetics* ; Cell Differentiation ; Neural Stem Cells ; Translocation, Genetic ; Ubiquitins/genetics* ; Ligases/genetics*

Objective: To explore physical health status and influencing factors of preschool children in Tibet, so as to provide a scientific reference and theoretical basis for the healthy development of physical fitness. Methods: Data were collected from children (3-6 years old) of Xizang national physical fitness monitoring, and a total of 1 521 preschool children were recruited who received questionnaire survey and physical fitness test. Independent sample t-test and one-way ANOVA were used to compare the differences in physical fitness indexes of preschool children in different groups. Chi square test and binary Logistic regression model were used to analyze the factors affecting physical health of preschool children. Results: The total qualified rate of physical fitness was 79.75%, among which the excellent rate was 3.16%, the good rate was 15.12%, the qualified rate was 61.47% and the unqualified was 20.25%. From the perspective of BMI, the excellent physical fitness rate (3.74%) and good physical fitness rate ( 17.47% ) were highest in healthy weight preschool children, and the qualified physical fitness rate of overweight preschool children (69.03%) was higher than that of obese (55.88%) and healthy weight preschool children (60.68%)( χ 2=53.56, P <0.01). From the perspective of ethnic, Tibetan children s physique proficiency (3.69%), good rate ( 17.13% ) than with the elevation of the Han nationality (0.74%, 5.88%), fraction defective (16.97%), lower than that of Han nationality (35.29%) ( χ 2=53.71, P <0.01); The results of chest circumference, skinfold thickness, body fat percentage, tennis throw distance, continuous jump of both feet, sitting forward bend and balance beam walking of Tibetan children were higher than those of Han children, and the results of quiet heart rate and standing long jump were lower than those of Han children ( t = 2.72 , 10.95, 9.66, 3.68, 3.88, 8.04, 3.56, 8.70, -4.39 , -4.40, P <0.01). Binary Logistic regression analysis showed that Tibetans ( OR =2.29), breastfeeding ( OR =1.51), body dynamics outdoor daily exercise duration 30-90 min (30-<60 min ;OR = 2.03 ; 60-90 min: OR =2.22) were positively correlated with physical health of preschool children ( P <0.05). Conclusions The total physical qualification rate of preschool children aged 3-6 years old in Tibet is lower than the national average. Ethnic group, feeding pattern during infancy, and physical activity are all factors that affected the physical fitness of preschool children in Tibet. It is of great significance to improve the physique of preschool children in Tibet to promote their sustainable and healthy development.

Objective To observe the therapeutic effect of probiotics combined with montelukast in children with Mycoplasma pneumoniae pneumonia(MPP)complicated with myocardial injury.Methods A total of 102 children with MPP and myocardial injury were selected as the study objects,and were randomly divided into control group and observation group,with 51 cases in each group.The control group was treated with montelukast,and the observation group was treated with probiotics based on the control group.The clinical efficacy,symptom resolution time,hospital stay,myocardial injury index,inflammatory cytokines,intestinal flora level and incidence of adverse reactions were compared between the two groups.Results The total effective rate of the observation group was 92.16％,which was significantly higher than 76.47％of the control group(P＜0.05).The disappearance time of symptoms of fever,cough,shortness of breath,chest tightness and chest pain and hospital stay in the observation group were significantly shorter than those in the control group(P＜0.05).After treat-ment,the levels of cardiac troponin T(cTnT),B-type natriuretic peptide(BNP),myoglobin(Mb)and cardiac fatty acid binding protein(H-FABP)in the observation group were significantly lower than those in the control group(P＜0.05);the levels of interleukin-1 receptor 1(IL-1R1),gamma-interferon(γ-IFN)and high mobility group protein 1(HMGB1)in the observation group were significantly lower than those inthe control group(P＜0.05);the number of Bifidobacteria,Lactobacillus aci-dophilus,Enterococcus faecalis and Bacillus cereus in the observation group were significantly higher than the control group,while the number of Escherichia coli and Salmonella were significantly lower than those in the control group(P＜0.05).There was no significant difference in the incidence of ad-verse reactions between the two groups(P＞0.05).Conclusion Probiotics combined with monte-lukast have good efficacy in MPP children with myocardial injury,which can shorten the time of symp-tom resolution and hospital stay,improve the indexes of myocardial injury in children,inhibit the lev-el of inflammatory cytokines,adjust the structure of intestinal flora disorder,and have good safety.

OBJECTIVE To evaluate the clinical efficacy and safety of original and generic entecavir(ETV) in the treatment of chronic hepatitis B. METHODS Domestic and foreign literatures were systematically reviewed to evaluate the efficiency and safety. Qualitative combined with quantitative methods were used to evaluate and analyze. RESULTS Meta-analysis results showed that there were no significant differences in HBV-DNA negative conversion rate, ALT normalization rate, serum HBeAg negative conversion rate, HBeAg serum conversion rate, HBeAg/HBeAb serum conversion rate and incidence of adverse reactions between generic and original ETVs after 12 and 48 weeks of medication. Subgroup analysis of different treatment courses showed no statistical significance in each index. CONCLUSION The results of this study shows no significant differences between the two drugs in terms of clinical efficacy and safety considerations. However, limited by the quality and quantity of included literature, a large sample and multicenter RCT is still needed to confirm the conclusion.