Background Air pollution exposure has a significant impact on maternal and child health. However, the research on the association between ambient ozone (O₃) exposure during pregnancy and the risk of premature birth in newborns is limited, and the conclusions are inconsistent. Objective To investigate the association of ambient O₃ exposure during pregnancy with the risk of preterm birth in Guangdong Province. Methods Data of pregnant women in Guangzhou from 2013 to 2019 and Foshan from 2018 to 2023 were collected, and O₃ concentrations during different trimesters were assessed according to maternal residential addresses. Bilinear interpolation was used to evaluate the concentrations of air pollution. A cohort study design was adopted in our study. Restricted cubic spline curves were used to evaluate the exposure-response relationship between O₃ exposure and preterm birth risk and explore potential exposure threshold of O₃. Logistic regression models were used to evaluate the association of O₃ exposure with preterm birth. Results A total of 702 924 pregnant women were included in this study, of whom 43 051 (6.12%) were preterm. The average O₃ exposure concentrations of pregnant women during the first, second, third, and whole trimesters were 95.51, 97.51, 100.60, and 97.87 μg·m⁻³, respectively. We observed J-shaped associations between O₃ exposure and preterm birth risk during the second, third, and whole trimesters of pregnancy using restricted cubic spline curves. This study found that there were threshold concentrations between O₃ exposure and preterm birth risk during different gestational periods, and the threshold concentrations in the first, second, third, and whole trimesters were 112.32, 99.83, 111.74, and 112.46 μg·m⁻³, respectively. During the second, third, and whole trimesters of pregnancy, after adjusting for maternal age, baby sex, pre-pregnancy body mass index, mode of delivery, baby birth weight, gestational diabetes, and gestational hypertension, the odds ratios (OR) of preterm birth were 1.02 (95%CI: 1.01, 1.04), 1.02 (95%CI: 1.00, 1.03), and 1.17 (95%CI: 1.13, 1.21) for each 10 μg·m⁻³ increase in O₃ concentration above the O₃ threshold. No significant association was found between O₃ exposure and the risk of preterm birth during the first trimester. Conclusion There is a nonlinear association between the risk of preterm birth and O₃ exposure during pregnancy, and higher concentrations of O₃ exposure during pregnancy are associated with the risk of preterm birth. Above the O₃ threshold concentration during pregnancy, especially during the second, third, and whole trimesters, the risk of preterm birth elevates with the increase of O₃ exposure concentrations.

ObjectiveTo investigate the mechanism of Atractylodis Macrocephalae Rhizoma（AMR） in the treatment of slow-transmission constipation（STC） by observing the effects of AMR on short-chain fatty acids and intestinal barries in STC mice. MethodForty-eight male KM mice were randomly divided into blank group， model group， AMR low-， medium-， high-dose groups（2.5， 5， 10 g·kg^-1） and mosapride group（2.5 mg·kg^-1）. Except for the blank group， all groups were gavaged with loperamide suspension（5 mg·kg^-1） twice daily for 14 d to construct the STC mouse model. At the same time， each drug administration group was given the corresponding drug by gavage for consecutive 14 d， the blank and model groups were gavaged with equal volume of distilled water. The effects of the treatment of AMR on body mass， defecation frequency， fecal water content and intestinal propulsion rate of mice were observed， the pathological changes of mouse colon were observed by hematoxylin-eosin（HE） staining and periodic acid-Schiff（PAS） staining， the levels of gastrin（GAS） and motilin（MTL） in serum were detected by enzyme-linked immunosorbent assay（ELISA）， gas chromatography-mass spectrometry（GC-MS） was used to detect the contents of short-chain fatty acids（SCFAs） in mouse feces， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to determine the mRNA and protein expression levels of zonula occludens-1（ZO-1）， Occludin， and Claudin-1 in the colon of mice. ResultCompared with the blank group， the body mass， defecation frequency， fecal water content and intestinal propulsion rate of mice in the model group were significantly decreased（P<0.05， P<0.01）， the arrangement of colonic tissues was disordered， and the number of goblet cells was reduced， the levels of GAS and MTL in serum were significantly decreased（P<0.01）， and the levels of SCFAs in the feces were on a decreasing trend， with the contents of acetic acid， propionic acid， butyric acid， isobutyric acid and valeric acid were significantly decreased（P<0.05， P<0.01）， the mRNA and protein expression levels of ZO-1， Occludin and Claudin-1 in the colonic tissues were significantly decreased（P<0.01）. The above results suggested that STC mouse model was successfully constructed. Compared with the model group， the body mass， defecation frequency， fecal water content and intestinal propulsion rate of mice in AMP administration groups all increased significantly（P<0.05， P<0.01）， the mucosal layer of the colonic tissues was structurally intact without obvious damage， and the number of goblet cells increased， serum levels of GAS and MTL were significantly increased（P<0.01）， the contents of SCFAs in the feces were all on a rising trend， with the contents of acetic， propionic， butyric and isobutyric acids rising significantly（P<0.05， P<0.01）， the mRNA and protein expression levels of ZO-1， Occludin and Claudin-1 in the colonic tissues were significantly increased（P<0.05， P<0.01）. ConclusionAMR is able to improve the constipation symptoms in STC mice， and its mechanism may be related to increasing the contents of SCFAs in the intestine as well as promoting the mRNA and protein expression levels of ZO-1， Occludin and Claudin-1 in the colon.

Objective To investigate the expression level of serum tRNA derived tRF-17-79MP9PP(tRF-17)in patients with breast cancer and evaluate its correlation with the prognostic of the patients.Methods The serum samples were collected from 70 patients with breast cancer admitted to Jiangsu Cancer Hospital during June 2016 and December 2019 and 25 age-matched healthy women,and the clinical data of the patients were recorded.The expression level of serum tRF-17 was detected by real-time fluorescence quantitative PCR(qRT-PCR).The receiver operating characteristics(ROC)curve was used to evaluate the diagnosis value of tRF-17 in breast cancer patients.The correlations of tRF-17 with blood inflammatory indicators and tumor markers were analyzed by Spearman correlation analysis.The deadline for follow-up was April 2023.The factors influencing the prognosis of breast cancer were analyzed by the univari-ate and multivariate COX regression analysis.Results The expression levels of serum tRF-17 in breast cancer patients(3.99[0.70,10.46])were significantly lower than that in healthy controls(14.09[5.14,21.34],Z=-3.575,P＜0.01).The area under the ROC curve of tRF-17 for diagnosing breast cancer was 0.742(95％CI:0.635-0.849,P＜0.01).The average survival time of patients with high expression of tRF-17 was significantly higher than that of patients with low expression(75.97 months vs 56.06 months,log-rank P＜0.01).The COX proportional hazards model analysis showed that lymph node metastasis and the expression level of serum tRF-17 were independent risk factors affecting the prognosis of the patients(HR=1.723,95％Cl:1.084-2.739,P＜0.05;HR=0.189,95％CI:0.041-0.862,P＜0.05).Conclusion Serum tRF-17 is low expressed in breast cancer patients,and its expression level is an inde-pendent risk factor affecting the prognosis of breast cancer patients,which may be used as a biomarker to evaluate the prognosis of the patients.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective To explore the feasibility of radiomics features combined with different machine learning methods based on CT scans to predict lymphovascular and perineural invasion in patient with gastric cancer.Methods A total of 142 patients with gas-tric cancer lymphovascular confirmed by operative pathological examination were retrospectively selected.Among all patients,there were 96 positive cases and 46 negative cases.Among 137 patients with perineural invasion,there were 76 positive cases and 61 nega-tive cases.The 3D-Slicer package was used for delineation,and the Pyradiomics package was used to extract radiomics features.All data were randomly divided into training set and test set in an 8∶2 ratio.Intraclass correlation coefficient(ICC),Pearson correla-tion analysis,least absolute shrinkage and selection operator(LASSO)algorithm were used for feature selection.Support vector machine(SVM),K-nearest neighbor(KNN),decision tree(DT),random forest(RF),extreme tree(ET),extreme gradient boosting(XGBoost),and LightGBM were used to compare the models of lymphovascular and perineural invasion,respectively.Receiver operating characteris-tic(ROC)curve and area under the curve(AUC)were used to evaluate the predictive performance of these models.Results The lymphovascular group AUC of SVM,KNN,DT,RF,ET,XGBoost,and LightGBM in the training set were 0.926,0.753,1.000,0.999,1.000,1.000,and 0.917,and the AUC in the test set were 0.894,0.692,0.456,0.678,0.753,0.650,and 0.650,respectively.The perineural invasion group AUC of SVM,KNN,DT,RF,ET,XGBoost,and LightGBM in the training set were 0.864,0.794,1.000,1.000,1.000,1.000,and 0.866,and the AUC in the test set were 0.861,0.706,0.700,0.672,0.731,0.667,and 0.678,respectively.Conclusion Based on venous phase CT radiomics features combined with machine learning methods,it is feasible to predict lymphovascu-lar and perineural invasion of gastric cancer preoperatively.Among the variousmachine learning methods,SVM shows the best predictive performance for lymphovascular and perineural invasion in patient with gastric cancer.

Objective To investigate the determinants of linezolid-associated neurological adverse reactions in patients with multidrug-resistant tuberculosis and develop a risk prediction model for such adverse events.Methods A prospective cohort study design was employed to select 120 patients with drug-resistant pulmonary tuberculosis who received a chemotherapy regimen containing linezolid at Guangzhou Chest Hospital from April 2023 to January 2024 as the study population.Clinical data,adverse reactions,and plasma concentration of linezolid were collected during fasting and at 2 hours post-medication.Univariate analysis and multivariate logistic regression were conducted to identify factors influencing linezolid-related neurological adverse reactions.Furthermore,a prediction model for such adverse reactions was developed,and its predictive efficacy and calibration ability were evaluated using ROC analysis.Results Re-treatment(OR=2.540,P=0.028),coexistence of cavities(OR=4.092,P=0.021),anemia(OR=10.921,P=0.005),and Cmin≥0.7665 mg/L(OR=6.813,P<0.001)are independent risk factors for the occurrence of linezolid-related neurological adverse reactions.The prediction model,based on these four factors,exhibits an AUC of 0.851(95%CI:0.774～0.929),accompanied by a Youden index of 0.590,a sensi-tivity of 66.7%,and a specificity of 92.3%.Moreover,the prediction model demonstrates excellent calibration ability.(Hosmer-lemeshow χ2=8.719,P=0.273).Conclusion In MDR/RR-TB patients,the presence of cavita-tion,retreatment,and anemia may confer a heightened risk of linezolid-related neurological adverse reactions.A risk prediction model incorporating these four indicators demonstrates significant predictive value for the occurrence of such adverse events.

Zinc ions are the most abundant trace elements in the human body,second only to iron.They function as critical second messengers in cells and are essential for maintaining the normal structure and function of proteins.Consequently,they are involved in a range of vital cellular processes,including cell cycle progression and division.The regulation of the intracellular zinc ion balance primarily depends on two major families of metal transporters:ZnT(SLC30 A)and ZIP(SLC39 A).In the con-text of cancer,the disruption of zinc ion homeostasis and the abnormal expression of zinc transporters are closely linked to tu-morigenesis and cancer progression.However,varying findings among studies regarding the specific roles of zinc ions and zinc transporters in cancer present a significant challenge for the development and clinical application of therapies targeting zinc ion homeostasis.This paper provides a comprehensive review and analysis of the functions of zinc ions and zinc transporters in canc-er,along with an overview of emerging therapeutic strategies targeting zinc ion homeostasis.

Objective To investigate the progression of breast cancer in mice induced by chronic binding stress and the regulatory mechanism of Xiaoyao SAN based on TGF-β1/CD147 signal pathway.Methods 40 BABL/c mice were randomly divided into tumor group,model group,Xiaoyaosan group and Mifepristone group,and then 4T1 cell line was inoculated into the armpits of each group of mice.After Tumor formation,mice in all groups except tumor group were subjected to chronic restraint stress for 21 days.Meanwhile,mice in Xiaoyaosan and Mifepristone groups were gavaged with the corresponding drugs,and mice in the other two groups were gavaged with normal saline.After the modeling,the mice were sacrificed after anaesthesia.The weight and volume of the tumors and visceral index of the mice were measured.The contents of serum tumor markers(CA199,CEA,VEGF),serum neurotransmitters(DA and CORT),and inflammatory mediators(TGF-β1 and IL-10)in tumor tissues were detected by Elisa.The expressions of iNOS and Arg-1,the polarization markers of macrophages,and the expressions of CD147 and its downstream signaling molecules MMP2,MMP9 and VEGF in tumor tissues were all detected by immunohistochemistry and Western blot.Results Compared with tumor group,in model group,tumor weight and volume,serum CA199,CEA,VEGF,CORT content,tumor TGF-β1 and IL-10 content were significantly increased;visceral index and serum DA content were significantly reduced;the expression of M2-type polarization marker Arg-1 in tumor macrophages was significantly increased,while the expression of M1-type polarization marker iNOS was significantly decreased;the expressions of CD147 and its downstream signaling molecules MMP2,MMP9 and VEGF were significantly increased.Both Xiaoyaosan and mifepristone could effectively reverse the above changes.Conclusion The mechanism of chronic restraint stress promoting breast cancer progression in mice is related to the increased release of TGF-β1 from M2-type polarization of tumor-associated macrophages,which activates CD147 and its downstream related signals.Xiaoyaosan could relieve the M2-type polarization of macrophages caused by increased corticosterone under stress conditions,reduce the production of TGF-β1,inhibit CD147 and its downstream signal,and thus inhibit the progression of breast cancer caused by chronic restraint stress in mice.

Objective:To analyze the clinical phenotype and genetic characteristics for a child with Canavan disease.Methods:A child who was admitted to the Children's Hospital Affiliated to Shandong University on April 9, 2021 for inability to uphold his head for 2 months and increased muscle tone for one week was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:Genetic testing revealed that the child has harbored compound heterozygous variants of the ASPA gene, including a paternally derived c. 556_559dupGTTC (p. L187Rfs*5) and a maternally derived c.919delA (p. S307Vfs*24). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:The c. 556_559dupGTTC (p.L187Rfs*5) and c. 919delA (p.S307Vfs*24) compound heterozygous variants of the ASPA gene probably underlay the pathogenesis of Canavan disease in this child.

Male ; Humans ; Aged ; Sleep Duration ; Aging ; Testosterone ; China ; Sleep