Background Large-for-gestational-age (LGA) births are associated with adverse perinatal outcomes and increased risks of offspring obesity, metabolic syndrome, and cardiovascular diseases later in life. Beyond traditional risk factors, exposure to environmental factors, especially fine particulate matter (PM_2.5), before and during pregnancy may contribute to excessive fetal growth; however, the roles of specific chemical constituents and critical exposure windows remain unclear. Objective To examine the associations between maternal exposures to PM_2.5 and its chemical constituents before and during pregnancy and the risk of delivering LGA infants. Methods Singleton pregnancies from the National Free Preconception Health Examination Project between 2010 and 2014 were included. Individual exposures to PM_2.5 and its constituents were estimated for preconception and pregnancy windows using geocoded residential addresses. The associations of single and mixed exposures with LGA risk were analyzed using generalized linear models (GLMs) and qg-computation. Results Exposures to PM_2.5 and its major chemical constituents were significantly associated with an increased LGA risk, with differences in effect magnitude across components. Secondary inorganic aerosols showed the strongest associations. For full-pregnancy exposure, nitrate (OR=1.330, 95%CI: 1.313, 1.347), ammonium (OR=1.279, 95%CI: 1.263, 1.295), and sulfate (OR=1.242, 95%CI: 1.227, 1.257) had larger effects on LGA risk than black carbon and organic matter. Analysis by exposure window indicated that the month preceding conception and the third trimester of pregnancy were critical exposure windows for susceptibility, while the strongest effect was observed for full-pregnancy exposure, suggesting a cumulative effect over time. Mixed exposure analysis further showed that nitrate and sulfate consistently accounted for the main positive contributions across different time windows. Conclusion Maternal exposures to PM_2.5 and its chemical components before and during pregnancy are associated with an elevated LGA risk. Nitrate and sulfate show consistent and strong associations across pregnancy stages, underscoring the importance of component composition and exposure timing in fetal overgrowth.

Objective: To examine the association between health behaviors and depressive symptoms among junior and senior high school students, so as to provide evidence for combined behavioral interventions targeting adolescent mental health. Methods: From September to November 2023, a stratified cluster random sampling method was used to recruit 104 834 junior and senior high school students from all 13 prefecture level cities (124 districts/counties) in Heilongjiang Province, China. Multivariable Logistic regression models, as well as multiplicative and additive interaction analyses were employed to analyze the associations between health behaviors and depressive symptoms, and Chi-square tests for trend were conducted to explore ,the changing tendency in the risk of depressive symptoms with increasing numbers of health behaviors among junior and senior high school students. Results: Healthy diet ( OR =0.66, 95% CI =0.63-0.68), healthy physical activity ( OR =0.47, 95% CI =0.45-0.49), healthy outdoor activity ( OR =0.55, 95% CI =0.52-0.57), healthy sleep ( OR =0.72, 95% CI =0.69-0.75), and healthy screen use ( OR =0.79, 95% CI =0.76-0.82) were independently associated with lower rates of depressive symptoms (all P <0.01). The risk of depressive symptoms decreased progressively with an increasing cumulative number of health behaviors ( χ 2 trend =996.73, P <0.01). Except for the interaction between healthy diet and healthy sleep, significant additive interactions were observed among the remaining health behaviors( RERI =0.07-0.23,all P <0.05). The probability of depressive symptoms was lower among girls with 2-3 healthy behaviors than among boys ( Z =2.51, 2.65), lower among urban students with 2-3 healthy behaviors than among suburban county students ( Z =-2.36, -2.04), and lower among senior high school students with 2-4 healthy behaviors than among junior high school students ( Z =2.17, 2.10, 2.04) (all P <0.05). Conclusions Health behaviors are significantly associated with depressive symptoms among junior and senior high school students. The probability of depressive symptoms is lower among girls, urban students, and senior high school students who engage in multiple healthy behaviors. Implementing combined interventions targeting multiple health behaviors in these populations may yield greater benefits.

ObjectiveMethylthioadenosine phosphorylase (MTAP) is found to be frequently deleted in malignant cancers, but the role of MTAP underlying metastasis and stemness of liver cancer remains far from clear. 5-fluorouracil (5-Fu) is clinically used in treating advanced liver cancer, however, chemoresistance is one of the major barriers impeding its efficacy. Liver cancer stem cells are considered to be the reservoir for tumor progression and chemoresistance. This study aims to explore the role of MTAP in regulating stemness and chemoresistance of 5-Fu in liver cancer. It is designed to elucidate the molecular mechanisms underlying MTAP-manipulated stemness. How MTAP influences metastasis and chemoresistance against 5-Fu in liver cancer is also elaborated. MethodsThe correlation of MTAP expression with stemness marker CD133 was evaluated by flow cytometry. Colony formation assays were conducted to analyze the tumorigenic ability. Western blot assays were applied to delineate the molecular mechanisms underlying MTAP-regulated stemness. Trans-well assays were conducted to analyze the metastatic potential of liver cancer cells.In vivo experiments were performed using subcutaneous xenograft and lung metastasis model on nude mice. Tumor size and weight were analyzed upon 5-Fu treatment. Metastatic nodules on lungs were evaluated. Immunohistochemical and TUNNEL assays were performed on slides obtained from tumor tissues. ResultsMTAP overexpression inhibited expression of CD133 and colony formation, which is further ablated by MTAP inhibitor. MTAP deprivation augmented stemness and colony formation, which is reversed by protein arginine methyltransferase 5 (PRMT5) overexpression but not its catalytically inactive counterparts. Critically, SRY-box transcription factor 2 (SOX2) was found to be a downstream regulator of MTAP/PRMT5, leading to stemness of liver cancer cells. MTAP overexpression suppressed SOX2 expression, while MTAP inhibition augmented expression of SOX2. Critically, MTAP overexpression inhibited migration and invasion of liver cancer cells. In vivo experiments in animal model found that MTAP deprivation promotes tumor growth and metastatic nodules of liver cancer. Additionally, MTAP overexpression inhibits tumor growth. Moreover, MTAP deprivation contributes to chemoresistance shown by increased tumor size and weight treated by 5-Fu. In contrast, MTAP overexpression led to further decline in tumor size and weight elicited by 5-Fu treatment. Accordingly, SOX2 was inhibited in tumor tissues after MTAP overexpression. Marker of proliferation Ki67 (Ki67) expression was dampened while apoptosis was found in MTAP-overexpressed tumor tissues. ConclusionIn this study, plethora of experimental studies collectively demonstrated that MTAP deprivation enhances stemness of liver cancer by regulating SOX2, exerting anti-cancer and chemoresistant role against 5-Fu in liver cancer. It is also worth noting that MTAP inhibition promoted metastasis of liver cancer. MTAP overexpression augmented tumor shrinking elicited by 5-Fu and SOX2 was involved in this process. These results concluded that MTAP/PRMT5/SOX2 signaling axis was involved in regulating stemness and chemoresistance of liver cancer. These findings help to exploit novel therapies by targeting stemness in MTAP-depleted liver cancer. It shed novel light on unveiling MTAP-regulated stemness in antagonizing 5-Fu treatment in liver cancer. It also adds mounting evidence to the theoretical basis for accomplishing personalized chemotherapy of liver cancer patients by targeting MTAP or its downstream PRMT5/SOX2.

OBJECTIVE To provide standardized whole-process guidance on drug traceability codes for medical institutions in Sichuan province， ensuring medication safety and compliance with medical insurance supervision requirements. METHODS Based on evidence-based principles and expert consensus， Expert Consensus on Whole-process Management of Drug Traceability Codes in Medical Institutions of Sichuan Province （hereinafter referred to as the Consensus） was formulated through systematic literature review， field investigations， establishment of a multidisciplinary expert committee and multiple rounds of questionnare consultation via the modified Delphi method， and finalized through consensus meetings. RESULTS & CONCLUSIONS The Consensus clarifies key operating procedures for code verification， code assignment and code return， whole-process operational standards for drug warehouse acceptance and storage， drug warehouse outbound delivery and pharmacy acceptance check， drug distribution and dispensing in pharmacy and intravenous admixture center， medication administration in nursing units and examination departments， as well as drug return process. Key recommendations are proposed such as improving the core functions of the drug traceability system， unifying the hospital-wide traceability code database， strengthening the management of traceability codes for backup medications， establishing a management organization and institutional framework， and optimizing the architectural design and data governance requirements of the drug traceability system. The release of the Consensus will provide scientific， standardized and implementable practical guidelines for medical institutions of Sichuan province， helping to improve closed-loop management of the drug traceability system， strengthen medication safety and fulfil medical insurance fund supervision.

The telomere structure in the cell nucleus is crucial for maintaining the stability and functions of chromosomes.Telomerase is a ribonucleoprotein reverse transcriptase,which catalyzes the elongation of telomeres using its own RNA as a template,thereby counteracting the shortening of telomeres caused by chromosome replication and cell division.Due to its overexpression in over 85％of malignant tumor cells,telomerase has emerged as a highly promising biomarker and a novel target for cancer therapy.In recent years,given the importance of precise quantification of telomerase activity in guiding medical diagnosis and treatment strategies,researchers have developed various high-performance telomerase detection techniques.Among these,electrochemical biosensing technique has cause much attention due to its high sensitivity,operational convenience,rapid response,and ease of miniaturization.This paper focused on the latest advances in electrochemical sensing technique for detection of telomerase activity,aiming to provide inspiration for designing novel telomerase activity detection strategies by elucidating three unique properties of telomerase primer extension products.

Objective:To explore the epidemiological characteristics, clinical manifestations, laboratory findings, and imaging features of children with HRV-associated pneumonia, and to analyze the clinical features and risk factors associated with severe HRV pneumonia, providing references for clinical management.Methods:A single-center, retrospective, observational study was conducted, including 1 001 cases of HRV-positive children with pneumonia admitted to the Respiratory Department of the Affiliated Children′s Hospital of Capital Institute of Pediatrics from January 2019 to December 2023. Among them, 584 cases (58.3%) were male and 417 cases (41.7%) were female, with an age range of 0.1 to 14.9 years, a median age of 3.42 years, and a mean age of (3.92±2.75) years. According to clinical guidelines, the cases were divided into a mild pneumonia group (855 cases, 510 males, 345 females) and a severe pneumonia group (146 cases, 73 males, 73 females). Basic information, clinical, laboratory, and imaging data were collected from the electronic medical record system. Comparisons between different age groups, diagnoses, and pneumonia severity groups were performed using the χ2 test. Multivariate logistic regression analysis was used to identify risk factors for the severity of HRV pneumonia. Results:Among the 1 001 cases of HRV-associated bronchopneumonia, 146 cases (14.6%) were severe pneumonia. The age of severe HRV pneumonia patients was significantly higher than that of the mild pneumonia group (5.2 years vs. 3.7 years, t=-6.050, P<0.01). Severe HRV pneumonia had a higher incidence in autumn and winter (60.9%). Severe HRV pneumonia was associated with higher levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), neutrophils, and creatinine (correlation coefficients 0.198, 0.334, 0.104, 0.142, P<0.01), and lower levels of albumin (correlation coefficient 0.308, P<0.01). Multivariate logistic regression analysis showed that co-infection with Streptococcus pneumoniae or Mycoplasma was an independent risk factor for severe HRV pneumonia [ OR=1.611, 95% confidence interval ( CI):1.066-2.435, P<0.05; OR=3.355, 95% CI:2.062-5.458, P<0.01]. Conclusion:The infection rate of HRV is higher in preschool and school-age children. Severe HRV pneumonia is associated with increased levels of LDH, CRP, neutrophils, and creatinine, as well as decreased levels of albumin. Co-infection with Streptococcus pneumoniae or Mycoplasma may be an independent risk factor for severe HRV pneumonia. High-risk children require enhanced monitoring and early intervention to improve prognosis.

Objective To construct a visual imaging decision model for evaluating the prognosis of hepatocellular carcinoma(HCC)patients treated with interventional therapy based on MRI features.Methods A total of 130 HCC patients were selected.All of them underwent MRI examination upon admission,and then the interventional therapy was implemented after clinical evaluation.The patients were followed up for 2 years after the last interventional therapy,and then were divided into poor prognosis group(50 cases)and good prognosis group(80 cases)according to the follow-up results.The risk factors affecting the poor prognosis of HCC patients treated with interventional therapy were screened.A nomogram model was constructed based on the risk factors,and its prediction efficiency was then evaluated.Results The incomplete capsule,unsmooth tumor margin,portal vein tumor thrombus,cirrhosis,apparent diffusion coefficient(ADC)value,red blood cell distribution width within 24 h after admission,and aspartate aminotransferase were significantly different between the poor prognosis group and the good prognosis group(P＜0.05),and these indicators were the risk factors affecting the poor prognosis of HCC patients treated with interventional therapy(P＜0.05).Based on the above risk factors,a nomogram model of poor prognosis risk for the HCC patients treated with interventional therapy was constructed,and the sensitivity,specificity,and area under the curve(AUC)for predicting poor prognosis of HCC patients treated with interventional therapy were 90.00％,81.80％and 0.899[95％confidence interval(CI)0.827-0.972],respectively.Conclusion The risk nomogram model of poor prognosis of HCC patients treated with interventional therapy based on incomplete capsule,unsmooth tumor margin,portal vein tumor thrombus,cirrhosis,ADC value,red blood cell distribution width,and aspartate aminotransferase has good predictive efficacy.

BACKGROUND:The cryopreservation technology enables tissues/cells to be stored for a long time in a low-temperature environment while maintaining the integrity of their activity and function,which is of great significance for the construction of cell therapy,tissue engineering and biological sample banks.Cryoprotective agents often contain dimethyl sulfoxide and serum.To avoid the toxic side effects of dimethyl sulfoxide,the complexity of serum components and immune responses,although some finished cryoprotective agents have been marketed,they are faced with many difficulties such as high cost and limited application.Therefore,there is an urgent need to develop a cryoprotective agent with clear components and the ability to solve the above problems.OBJECTIVE:To evaluate the effects of a novel cryoprotectant on cryopreservation efficiency of different tissue and cell sources.METHODS:By applying the novel cryoprotectant as an experimental group with the commercially available and widely used cryoprotectant(control group)to umbilical cord Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,NK and CIK cells,comparative analyses were conducted in terms of cell morphology,number,viability,surface markers,differentiation potential,and cell-killing toxicity assay before cryopreservation and after resuscitation thawing.We confirmed the cryopreservation effect of the new cryoprotectant and its potential application value.RESULTS AND CONCLUSION:(1)The novel cryoprotectant facilitated the normal growth of cryopreserved Wharton's jelly tissue upon recovery,exhibiting mesenchymal stem cell morphology.No significant differences were observed between the experimental and control groups in terms of cell recovery rate,surface markers,and differentiation potential.(2)There was no significant difference in the number and viability of cells between the experimental group and the control group after cryopreservation of cord blood/peripheral blood mononuclear cells,and the cryo-resuscitated cell numbers and viability of derived NK cells/CIK cells did not show significant difference between the experimental and control groups.(3)For NK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportion of CD56+CD16+cell subpopulations between the experimental group and the control group.For CIK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportions of CD3+CD8+and CD3+CD56+cell subpopulations between the experimental group and the control group.(4)In terms of cytotoxicity testing,when the effective-target ratio of immune cells and melanoma cell line Mel624 was 20:1,whether it was NK cells/CIK cells derived from cord blood or peripheral blood mononuclear cells,there was no significant difference in the tumoricidal activity of cells between the experimental group and the control group.These findings suggest that the novel cryoprotectant can replace existing commercially available and widely used cryoprotectants,and is applicable to Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,as well as NK and CIK cells,providing a solid technical foundation for the scaling,standardization,and commercialization of universal cryoprotectants.

Objective To investigate whether successful percutaneous coronary intervention(PCI)could improve symptoms and quality of life(QOL)in left main disease and/or 3-vessel disease patients with diabetes.Methods Patients with left main disease and/or 3-vessel disease who underwent PCI in the First Affiliated Hospital of Air Force Medical University from April 2018 to May 2021 were consecutively enrolled and subdivided into 2 groups:diabetes and no diabetes.Detailed baseline characteristics,symptoms,including dyspnea and angina,assessed with the Rose dyspnea scale(RDS),Seattle angina questionnaire(SAQ),the European quality of life-5 dimensions(EQ-5D)and 12-item short-form health survey(SF-12)questionnaire respectively,procedural details,and 1 month and 1 year follow-up data were collected.Results Among 440 left main disease and/or 3-vessel disease patients,disease was present in 176(40.00％),who had more hypertension,peripheral artery disease,and LCX lesion(all P＜0.05).The incidence of major adverse cardiovascular events(MACE)and all-cause mortality were similar between the two groups(both P＞0.05)at 1 month follow-up,while all-cause mortality in diabetes patients was significantly higher than those without diabetes at 1 year follow-up(P=0.013).Low left ventricular ejection fraction was an independent risk factor for MACE and all-cause mortality at 1 month and 1 year follow-up after successful revascularization(all P＜0.05).Most importantly,symptoms,including dyspnea and angina,and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up(all P＜0.05).Diabetes patients showed improved dyspnea and QOL at similar degree to the non-diabetes patients(all P＞0.05)and a more significantly relieved angina(P=0.013).Additionally,the number of chronic total occlusion(CTO)per patient was identified as an independent risk factor of dyspnea(OR 0.723,95％CI 0.525～0.997,P=0.048)and angina relief(OR 0.686,95％CI 0.473～0.995,P=0.047),and the contrast volume(OR 0.995,95％CI 0.992～0.999,P=0.008)as an independent risk factor of QOL improvement in diabetic patients.Conclusions Successful PCI is beneficial for relieving symptoms and improving quality of life in patients with diabetes who have left main disease and/or 3-vessel disease.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.