ObjectiveTo investigate the relationship between the non-fasting triglyceride and glucose （TyG） index and hyperglycemia in pregnancy during the third trimester in high altitudes. MethodsThis study selected clinical and laboratory data of 774 Tibetan singleton pregnant women who delivered at Chaya People's Hospital of Qamdo city in Xizang autonomous region， from January 2023 to April 2025. The non-fasting TyG index was calculated from non-fasting triglyceride （TG） and random plasma glucose （PG）. Based on the tertiles of the non-fasting TyG index values， the individuals were split into three groups （corresponding to non-fasting TyG index of 8.89 and 9.21， respectively）. The baseline clinical characteristics， lipid levels and the occurrence of developing hyperglycemia in pregnancy were compared among the three groups. Statistical analyses were performed using ANOVA， Kruskal-Wallis H test， Chi-square test， or Fisher exact test and the relationship between the non-fasting TyG index and hyperglycemia in pregnancy were examined using multivariate logistic regression models and curve fitting. ResultsA total of 774 Tibetan singleton pregnant women were included， with a average age of 27.3 ± 6.1 years， a pre-delivery body mass index （Pre-BMI） of （25.2±2.3）kg/m² ， a proportion of 26.7% （207/774） primigravid women， the mean non-fasting TyG index was 9.1 ± 0.4。Thirty pregnant women were diagnosed with hyperglycemia in pregnancy， with a detection rate of 3.9% （30/774）. Statistically significant differences in serum total cholesterol （TC）， TG， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） levels were identified when comparing different non-fasting TyG groups （all P values <0.05）. Subsequent trend test analysis indicated that the levels of TC， TG， LDL-C， and PG gradually increased with elevated the non-fasting TyG index （ F_{trend TC}=95.61， P<0.001； F_{trend TG}=1 051.91， P<0.001； F_{trend LDL-C} = 97.20， P < 0.001； F_{trend TG}=195.20； P<0.001）. After adjustment for maternal age， pre-delivery BMI， altitude， TC， LDL-C， and HDL-C， multivariate Logistic regression models revealed independent positive associations between non-fasting TyG index and hyperglycemia in pregnancy （Model 1： OR=2.72， 95% CI： 1.13-6.53， P=0.026； Model 2： OR=2.56， 95% CI： 1.01-6.50， P=0.048； Model 3： OR=2.72， 95% CI： 1.06-6.97， P=0.037； Model 4： OR=4.02， 95% CI： 1.42-11.40， P=0.009） and the incident of hyperglycemia in pregnancy showed an increasing tendency as increasing with the non-fasting TyG index， however， this association did not statistical significance （P _trend >0.05）. Curve fitting by restricted cubic splines （RCS） were used to assess linearity between non-fasting TyG and hyperglycemia in pregnancy， and there was a linear dose-response relationship between non-fasting TyG and hyperglycemia in pregnancy （P _{for non-linear} = 0.515）. ConclusionNon-fasting TyG index in the third trimester is a risk factor for hyperglycemia in pregnancy among the Tibetan singleton pregnant women at high altitudes and there was a possible linear dose-response relationship between the non-fasting TyG index and hyperglycemia in pregnancy.

OBJECTIVE: To investigate the role of telomerase reverse transcriptase (TERT) in alleviating doxorubicin (DOX)-induced cardiotoxicity. METHODS: (1) Cell experiments: rat H9c2 cardiomyocytes were divided into control group (CON group), null adenovirus transfection group (NC group), TERT overexpression adenovirus transfection group (TERT group), DOX group (treated with 1 μmol/L DOX for 12 hours), DOX+NC group, and DOX+TERT group (null adenovirus or TERT overexpression adenovirus were transfected for 24 hours and then treated with 1 μmol/L DOX for 12 hours). The mRNA expression of TERT in cardiomyocytes was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The level of mitochondrial membrane potential was detected by immunofluorescence. The expression levels of intracellular Bax, Bcl-2, microtubule-associated protein 1 light chain 3 (LC3) and p62 were detected by Western blotting. (2) Animal experiments: male C57BL/6 mice were randomly divided into a sham operation group (Sham group), DOX group (acute cardiotoxicity model was constructed by intraperitoneal injection of DOX 15 mg/kg), DOX+NC group and DOX+TERT group (modeled after transfection with airborne adenovirus or TERT overexpression adenovirus for 7 days). After 7 days of modeling, the area of myocardial fibrosis was detected by Sirius scarlet staining, and cardiac function was detected by echocardiography. RESULTS: (1) Cellular experiments: the mRNA expression level of TERT was significantly higher in the TERT group compared with the CON and NC groups. Compared with the CON group, the TERT mRNA expression level of cardiomyocytes in the DOX group and the DOX+NC group were significantly lower, the level of mitochondrial membrane potential was significantly lower, the protein expressions of Bax and LC3 were significantly increased, and the protein expressions of Bcl-2 and p62 were significantly decreased. No significant differences were found between the DOX group and DOX+NC group. Compared with the DOX group and DOX+NC group, the TERT mRNA expression level was increased in the DOX+TERT group (relative expression: 1.02±0.10 vs. 0.61±0.05, 0.54±0.03, both P < 0.05), the level of mitochondrial membrane potential was significantly increased (1.14±0.05 vs. 0.96±0.01, 0.96±0.01, both P < 0.05), the protein expressions of Bax and LC3 were significantly decreased, and the protein expressions of Bcl-2 and p62 were significantly increased (Bax/β-actin: 0.88±0.01 vs. 1.31±0.02, 1.26±0.01; LC3-II/I: 2.16±0.05 vs. 2.64±0.06, 2.58±0.02; Bcl-2/β-actin: 0.65±0.01 vs. 0.40±0.01, 0.41±0.01; p62/β-actin: 0.45±0.01 vs. 0.23±0.02, 0.29±0.01; all P < 0.05). (2) Animal experiments: compared with the Sham group, the percentage of myocardial fibrosis area was significantly increased and left ventricular ejection fraction (LVEF) and fractional shortening (FS) were significantly decreased in the DOX group and DOX+NC group. Compared with the DOX group and DOX+NC group, the percentage of myocardial fibrotic area was significantly decreased in the DOX+TERT group (%: 2.33±0.06 vs. 3.76±0.07, 3.87±0.06, both P < 0.05), and the LVEF and FS were significantly increased [LVEF (%): 67.00±1.14 vs. 54.60±1.57, 53.40±2.18; FS (%): 38.60±0.51 vs. 30.60±1.10, 30.00±0.71; all P < 0.05]. CONCLUSION Up-regulation of TERT expression can inhibit DOX-induced cardiomyocyte autophagy and apoptosis, attenuate DOX-induced myocardial fibrosis in mice, improve cardiac function, and thus alleviate DOX-induced cardiotoxicity.
Animals ; Doxorubicin/toxicity* ; Telomerase/metabolism* ; Myocytes, Cardiac/metabolism* ; Rats ; Male ; Cardiotoxicity ; Mice, Inbred C57BL ; Mice ; Membrane Potential, Mitochondrial ; Adenoviridae ; bcl-2-Associated X Protein/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Transfection ; Apoptosis

OBJECTIVE To establish a core competency evaluation system for drug clinical trial quality management personnel in China and validate its application. METHODS Based on the scope of work， responsibilities， and role positioning of quality management personnel in drug clinical trials， a preliminary draft of the core competency evaluation system was constructed through literature analysis and expert consultation. The draft was refined through a Delphi method involving 17 experts who provided feedback and revisions， ultimately forming a complete evaluation system. The developed system was applied to conduct electronic surveys from March to May 2024 among 110 quality management personnel from 38 drug clinical trial institutions， comparing their scores on indicator importance and self-assessed capabilities. RESULTS The response rate of both rounds of questionnaire survey was 100%， with Kendall’s W coefficients of 0.256 and 0.277 （P＜0.001 for both）， and an expert authority coefficient of 0.946. The finalized evaluation system for core competencies of clinical trial quality management personnel comprised 9 primary indicators， covering individual professional competence， communication skills， implementation condition verification， informed consent process review， clinical trial execution monitoring， adverse event disposal， reporting and documentation， trial record examination， trial report auditing， and inspection of other tasks， and 107 secondary indicators. Empirical research revealed significant discrepancies between importance scores and self-assessed competency scores across 70 indicators among 110 respondents （P＜0.05）. Indicators with relatively notable gaps between importance scores and self-assessed competency scores included in-depth understanding of Good Clinical Practice （GCP） requirements （0.34-point gap）， familiarity with national and institutional clinical trial inspection priorities （0.24-point gap），etc. CONCLUSIONS The indicator system constructed in this study has good scientificity and reliability. Clinical trial quality management personnel demonstrate deficiencies in multiple critical competencies， highlighting the urgent need for targeted training programs to enhance their overall professional capabilities.

Purpose To detect the expression of peroxiso-mal membrane protein 4(PXMP4)in breast cancer tissues and to explore the effect of PXMP4 on the proliferation,invasion,and epithelial-mesenchymal transition(EMT)of breast cancer cells.Methods Bioinformatics and immunohistochemistry(IHC)were used to detect the expression of PXMP4 in breast cancer tissues.In breast cancer cells,Western blot was used to detect the expression of Cyclin D1,E-cadherin,vimentin and N-cadherin after knockdown and overexpression of PMXP4.The proliferation ability of breast cancer cells was analyzed by CCK-8 and plate cloning assay.Scratch healing and Transwell assay an-alyzed the migration and invasion ability of breast cancer cells.Lentivirus was used to construct a PXMP4-silenced MCF-7 cell line,and the PXMP4-silenced MCF-7 cells were injected into the subcutaneous or tail vein of mice to observe lung metastasis and the number of subcutaneous tumors.Results Bioinformat-ics and IHC showed that the expression of PXMP4 in breast cancer tissues was significantly increased(P＜0.05),and the prognosis of breast cancer patients with high expression of PXMP4 was poor(P＜0.05).The clinicopathological analysis showed that the expression of PXMP4 was correlated with tumor grade and lymph node metastasis(P＜0.05).In vitro knock-down of PMXP4 inhibited the proliferation,invasion and EMT process of breast cancer cells(P＜0.05).Conversely,overex-pression of PXMP4 promoted the proliferation,invasion and EMT process of breast cancer cells(P＜0.05).In vivo,the number of lung metastases,the size of subcutaneous tumor,and the expression of Ki67 in tumor tissue were significantly de-creased after silenced PXMP4(P＜0.05).Conclusion PXMP4 is related to tumor grading and lymph node metastasis.PXMP4 promotes proliferation,invasion and EMT process of breast cancer cells.

Objective:To investigate the association between serum uric acid,pulmonary function and airflow obstruction in Chinese Taiwan healthy subjects.Methods:All the cross-sectional analysis was performed in the population over 40 years old using the physical examination data of Chinese Taiwan MJ Health Resource Center between 1996 and 2016 stratification by gender.The correlation analyses between serum uric acid were done and multivariate Logistic regression analysis was used to explore the effect of serum uric acid on airflow obstruction.Results:A total of 35 465 people were included in the study,in-cluding 16 411 men and 19 054 women.Among them,the serum uric acid concentration of men was higher than that of women,and the serum uric acid concentration of the people with airflow obstruction was higher than that of the people without airflow obstruction.There was a negative correlation between serum uric acid level and the forced expiratory volume in one second(FEV1)and the force vital capacity(FVC)in women(P＜0.05),but in men the correlation didn't exist(P＞0.05).After adjusting for age,education,smoking status,drinking status,work strength,body mass index,history of cough,his-tory of hypertension,history of diabetes,history of dyslipidemia,white blood cells and blood albumin,the airflow obstruction in women was more likely to exist with the serum uric acid elevated(OR=1.12,95％CI:1.02-1.22,P＜0.05).The results showed that women with hyperuricemia were more likely to have airflow obstruction than those without hyperuricemia(OR=1.36,95％CI:1.06-1.75,P＜0.05).There was no correlation between serum uric acid concentration and airflow obstruction in men(OR=1.04,95％CI:0.96-1.13,P＞0.05),also the hyperuricemia and airflow obstruction(OR=1.12,95％CI:0.89-1.39,P＞0.05).Conclusion:There is a negative correlation between serum uric acid and FEV1 and FVC in relatively healthy women,and there is an association between elevated serum uric acid and airflow obstruction in women,but not in men.Further prospective studies are needed to explore whether high serum uric acid level can increase the risk of airflow obstruction.

Objective To examine the quinolone resistance and mechanisms of resistance,including prevalence of transferable mechanisms of quinolone resistance(TMQR)genes in carbapenem-resistant Klebsiella pneumoniae(CRKP).Methods Antimicrobial susceptibility was tested for CRKP isolated from 7 hospitals in China during 2019 by broth microdilution method.Genome sequencing analysis was performed on Illumina HiseqX sequencing platform.The virulence genes,multilocus sequence typing(MLST),chromosome quinolone resistance-determining region(QRDR)variation,and prevalence of TMQR genes in CRKP were analyzed.Results Overall,98.4％and 99.2％of the 481 CRKP strains were non-susceptible to levofloxacin and ciprofloxacin,respectively.ST11(77.8％)and ST15(15.8％)were the dominant clones.Among the 303 CRKP strains carrying virulence gene(CV-CRKP),ST11 type and ST15 type strains accounted for 92.1％and 5.0％,respectively,while ST11 and ST15 type strains accounted for 53.4％and 34.3％in the 178 CRKP strains without the virulence gene(non-CV-CRKP).All of the ST11 and ST 15 type strains were resistant to quinolones associated with gyrA and parC mutation.All of the quinolone-sensitive strains were not ST11 type or not ST15 type.TMQR analysis showed that qnrS1(61.1％,294 strains),qnrB4(10.0％,48 strains)and aac(6)-Ib-cr(18.7％,90 strains)were most prevalent in CRKPs,while qnrB1(4 strains),qnrB2(2 strains),qnrD1(2 strains)and qnrB6(1 strain)were infrequently identified in CRKPs.Specifically,qnrB4 was mainly identified in high-level levofloxacin-resistant strains(MIC≥8 mg/L),while aac(6)-Ib-cr was found mainly in ciprofloxacin-resistant strains(MIC＞8 mg/L).Conclusions Clinical CRKPs were highly resistant to quinolone.The rate of QRDR variation were high in quinolone resistant CRKP strains,with high TMQR gene carriage.

Objective:To explore the effect of sinomenine(SIN)on LPS-induced apoptosis and autophagy of lung epithelial cells through the JNK/c-Jun signaling pathway.Methods:MLE-12 lung epithelial cells were cultured,and the toxicity of SIN was detected by CCK-8.Apoptosis was detected by flow cytometry,the number of autophagosomes was detected by immunofluorescence,and the expression levels of apoptosis,autophagy and JNK/c-Jun signaling pathway-related proteins were detected by Western blot.Results:After LPS modeling,apoptosis rate and the number of autophagosomes were increased,the protein levels of Cleaved caspase-3,Bax,and Beclin-1,and LC3Ⅱ/LC3Ⅰ,p-JNK/JNK and p-c-Jun/c-Jun were increased(P<0.05);Bcl-2 and P62 protein levels were decreased(P<0.05).SIN treatment can significantly improve the effects of LPS on apoptosis and autophagy,as well as the regulation of the JNK/c-Jun signaling pathway(P<0.05).Treatment with the autophagy inhibitor 3-MA or the JNK agonist ANISO could partially reverse the protective effect of SIN on LPS-induced lung epithelial cells(P<0.05).Conclusion:SIN may increase autophagy and pro-tect lung epithelial cells damaged by LPS by regulating proteins related to the JNK/c-Jun signaling pathway.

Objective To investigate the correlation between gene polymorphisms of coagulation factor Ⅻ(FⅫ)rs1801020 and resistin rs1862513 and unexplained recurrent spontaneous abortion(URSA).Methods A total of 189 patients diagnosed with URSA and 191 healthy postpartum women during the same period were selected from the obstetric clinic of Changning Maternity and Infant Health Hospital from January 2020 to December 2022.The probe PCR was used to detect gene polymorphisms of rs1801020 and rs1862513 in peripheral blood,and the differences in genotype distribution between the groups were observed.Results The frequencies of geno-types and alleles for F Ⅻ rs1801020 in the URSA-A group were 4.9％(CC),35.7％(CT),59.5％(TT),22.7％(C),and 77.3％(T),respectively.In the control A group,the frequencies were 8.0％(CC),47.1％(CT),44.9％(TT),31.5％(C)and 68.5％(T).The frequencies of genotypes and alleles for resistin rs1862513 in the URSA-B group were 11.3％(CC),47.3％(CG),41.4％(GG),34.9％(C)and 65.1％(G).In the control B group,the frequencies were 10.2％(CC),34.1％(CG),55.7％(GG),27.3％(C)and 72.7％(G).There was no significant difference in genotype frequency of the two loci(P＞0.05),but there was a sig-nificant difference in allele frequency(P＜0.05).The distribution frequency of F Ⅻ rs1801020 T allele in the URSA group was higher than that in the control group(X2=6.32,OR=1.567,95％CI:1.100-2.238,P=0.012).The distribution frequency of resistin rs1862513 G allele in URSA group was lower than that in con-trol group(X2=4.96,OR=1.433,95％CI:1.050-1.969,P=0.026).The mutation of F Ⅻ rs1801020 C to T was a risk factor for the occurrence of URSA,while the mutation of rs1862513 C to G was a protective factor for the occurrence of URSA(P＜0.05).The combined genotype analysis showed that compared to the popu-lation carrying the rs1801020 CC+rs1862513 CC genotype combination,the population carrying the rs1801020 TT+rs1862513 CG genotype had a significantly higher risk of URSA(OR=5.684,95％CI:1.210-30.920,P=0.035).Conclusion FⅫ rs1801020 T allele may increase the risk of URSA and resistin rs1862513 G al-lele may the risk of URSA.People with rs1801020 TT+rs1862513 CG genotype combination is more likely to develop URSA than those with rs1801020 CC+rs1862513 CC genotype combination.