, Available online , doi: 10.3967/bes2024.151
The thresholds and the methods for estimating the optimal serum 25-hydroxyvitamin D [25(OH)D] thresholds have not reached a consensus. Bone turnover markers (BTMs) as well as GC gene polymorphisms, were reported to be associated with vitamin D status. Therefore, this study aimed to investigate possible 25(OH)D cutoffs for the associations between 25(OH)D and BTMs, and how GC gene variation influences such cutoffs in Chinese women of childbearing age. In total, 1505 non-pregnant or non-lactating women (18–45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds. The median serum 25(OH)D was 16.63 (11.96–22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84-15.23) ng/mL], β-CTX [13.94 (12.49–15.39) ng/mL], and P1NP [13.87 (12.37–15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68–13.91) ng/mL], β-CTX [12.23 (10.22–14.23) ng/mL], and P1NP [11.85 (10.40–13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81–13.68) ng/mL], β-CTX [13.05 (11.78–14.32) ng/mL], and P1NP [12.81 (11.57–14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued. In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
, Available online , doi: 10.3967/bes2025.005
Objective This study examines utilizes the advantages of machine learning algorithms to discern key determinants in prognosticate postoperative circulatory complications (PCCs) for older patients. Methods This secondary analysis of data from a randomized controlled trial involved 1720 elderly participants in five tertiary hospitals in Beijing, China. Participants aged 60-90 years undergoing major non-cardiac surgery under general anesthesia. The primary outcome metric of the study was the occurrence of PCCs, according to the European Society of Cardiology and the European Society of Anaesthesiology diagnostic criteria. The analysis metrics contained 67 candidate variables, including baseline characteristics, laboratory tests, and scale assessments. Results Our feature selection process identified key variables that significantly impact patient outcomes, including the duration of ICU stay, surgery, and anesthesia; APACHE-II score; intraoperative average heart rate and blood loss; cumulative opioid use during surgery; patient age; VAS-Move-Median score on the 1st to 3rd day; Charlson comorbidity score; volumes of intraoperative plasma, crystalloid, and colloid fluids; cumulative red blood cell transfusion during surgery; and endotracheal intubation duration. Notably, our Random Forest model demonstrated exceptional performance with an accuracy of 0.9872. Conclusion We have developed and validated an algorithm for predicting PCCs in elderly patients by identifying key risk factors.
, Available online , doi: 10.3967/bes2024.152
Objective Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms. Methods In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods (GNRs) and tetrahedral framework nucleic acids (tFNA) loaded with the anti-tumor drug doxorubicin (DOX). Results Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation. Conclusion This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.
Bingsong Zhang,
Haibin Yu,
Xin Peng,
Haiyi Yan,
Siran Li,
Shutong Luo,
Renhuizi Wei,
Zhujiang Zhou,
Yalin Kuang,
Yihuan Zheng,
Chulan Ou,
Linhua Liu,
Yuehua Hu,
Jindong Ni
, Available online , doi: 10.3967/bes2025.024
Objective Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. Methods We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. Results We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011–2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four perfluoroalkyl substances (PFAS) and gout risk (2007–2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. Conclusion GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
, Available online , doi: 10.3967/bes2025.022
Objective Burning solid cooking fuel contributes to household air pollution and is associated with frailty. However, how solid cooking fuel use contributes to the development of frailty has not been well illustrated. Methods This study recruited 8,947 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study, 2011–2018. Group-based trajectory modeling was employed to identify frailty trajectories. Multinomial logistic regression was used to assess the association between solid cooking fuel use and frailty trajectories. Population-attributable fractions were used to estimate the frailty burden from solid fuel use. Results We identified three frailty trajectories: low-stable (n = 5,789), moderate-increasing (n = 2,603), and fast-increasing (n = 555). Solid fuel use was associated with higher odds of being in the moderate-increasing (OR: 1.24, 95% CI: 1.08–1.42) and fast-increasing (OR: 1.48, 95% CI: 1.14–1.92) trajectories. These associations were strengthened by longer solid fuel use (P for trend < 0.001). Switching to clean fuel significantly reduced the risk of being in these trajectories compared with persistent solid fuel users. Without solid fuel, 8% of moderate- and 19% of fast-increasing trajectories demonstrated frailty development like the low-stable group. Conclusion Solid cooking fuel use is associated with frailty trajectories in middle-aged and older Chinese populations.
, Available online , doi: 10.3967/bes2025.021
Objective To explore the protective effects and underlying mechanisms of H2S against lipid peroxidation-mediated carbonyl stress in the uranium-treated NRK-52E cells. Methods Cell viability was evaluated using CCK-8 assay. Apoptosis was measured using flow cytometry. Reagent kits were used to detect carbonyl stress markers malondialdehyde, 4-hydroxynonenal, thiobarbituric acid reactive substances, and protein carbonylation. Aldehyde-protein adduct formation and alcohol dehydrogenase, aldehyde dehydrogenase 2, aldo-keto reductase, nuclear factor E2-related factor 2 (Nrf2), and cystathionine β-synthase (CBS) expression were determined using western blotting or real-time PCR. Sulforaphane (SFP) was used to activate Nrf2. RNA interference was used to inhibit CBS expression. Results GYY4137 (an H2S donor) pretreatment significantly reversed the uranium-induced increase in carbonyl stress markers and aldehyde-protein adducts. GYY4137 effectively restored the uranium-decreased Nrf2 expression, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2, accompanied by a reversal of the uranium-decreased expression of CBS and aldehyde-metabolizing enzymes. The application of CBS siRNA efficiently abrogated the SFP-enhanced effects on the expression of CBS, Nrf2 activation, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2 and concomitantly reversed the SFP-enhanced effects of the uranium-induced mRNA expression of aldehyde-metabolizing enzymes. Simultaneously, CBS siRNA reversed the SFP-mediated alleviation of the uranium-induced increase in reactive aldehyde levels, apoptosis rates, and uranium-induced cell viability. Conclusion H2S induces Nrf2 activation and nuclear translocation, which modulates the expression of aldehyde-metabolizing enzymes and the CBS/H2S axis. Simultaneously, the Nrf2-controlled CBS/H2S axis may at least partially promote Nrf2 activation and nuclear translocation. These events form a cycle-regulating mode through which H2S attenuates the carbonyl stress-mediated NRK-52E cytotoxicity triggered by uranium.
, Available online , doi: 10.3967/bes2025.019
Objective To analyze the prevalence and burden of headache disorders in China and its provinces from 1990 to 2021. Methods Using data from the Global Burden of Disease Study (GBD) 2021, the number of prevalent cases, prevalence rate, disability-adjusted life years (DALYs), and age-standardized DALY rates were analyzed by sex, age group, and province for headache disorders and their subtypes (migraines and tension-type headaches [TTHs]) between 1990 and 2021. Percentage changes during this period were also estimated. Results In 2021, approximately 426 million individuals in China were affected by headache disorders, with an age-standardized prevalence rate of 27,582.61/100,000. The age-standardized DALY rate for all headache disorders was 487.15/100,000. Between 1990 and 2021, the number of prevalent cases increased by 37.78%, while the prevalence of all headache disorders, migraines, and TTHs increased by 6.92%, 7.57%, and 7.86%, respectively. The highest prevalence was observed in the 30–34 age group (39,520.60/100,000). Migraine accounts for a larger proportion of DALYs attributable to headache disorders, whereas TTH has a greater impact on its prevalence. In 2021, the highest age-standardized DALY rates for headache disorders were observed in Heilongjiang (617.85/100,000) and Shanghai (542.86/100,000). Conclusion The prevalence of headache disorders is increasing in China. Effective health education, improve diagnosis and treatment are essential, particularly for middle-aged working populations and women of childbearing age.
, Available online , doi: 10.3967/bes2025.020
Objective Cigarette smoking exacerbates progression of pulmonary tuberculosis (TB) . The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention, but it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aims to analyze the characteristics of pulmonary TLS in smoking TB patients and therefore to explore the possible role of TLS in smoking-related lung injury in TB. Methods Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection due to pulmonary TB were included in this study. Pathological and immunohistological analysis was conducted to evaluate the quantity of TLS, and chest CT was used to assess the severity of lung lesions. The correlation between TLS quantity and TB lesion severity scores was analyzed. Immune cells and chemokines for TLS formation were also evaluated and compared between smoker and nonsmoker patients. Results Smoking TB patients had significantly more TLS than non-smokers (P < 0.001). TLS quantity in both lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and CXCL13 expression in smoker patients with TB (P < 0.001). Conclusion Smoking TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
, Available online , doi: 10.3967/bes2025.018
Objective To describe survival trends and global patterns of esophageal cancer (EC) using survival data from population-based cancer registries. Methods We systematically searched PubMed, EMBASE, Web of Science, SEER, and SinoMed databases for articles published up to 31 December 2023. Eligible EC survival estimates were evaluated according to country or region, period, sex, age group, pathology, and disease stage. Results After 2010, Jordan exhibited the highest age-standardized 5-year RSRs/NSRs at 41.1% between 2010 and 2014, while India had the lowest, at 4.1%. Survival rates generally improved with diagnostic age across most countries, with significant increases in South Korea and China, of 12.7% and 10.5% between 2000 and 2017, respectively. Survival was higher among women compared to men, ranging from 0.4%-10.9%. Survival rates for adenocarcinoma and squamous cell carcinoma were similar, differing by about 4%. In China, the highest age-standardized RSRs/NSRs was 33.4% between 2015 and 2017. Meanwhile, the lowest was 5.3%, in Qidong (Jiangsu province) between 1992-1996. Conclusion Global EC survival rates have improved significantly in recent decades, but substantial geographical, sex, and age disparities still exist. In Asia, squamous cell carcinoma demonstrated superior survival rates compared to adenocarcinoma, while the opposite trend was observed in Western countries. Future research should clarify the prognostic factors influencing EC survival and tailor prevention and screening strategies to the changing EC survival patterns.
Xiaobing Liu,
Jun Wang,
Yajie Li,
Hongxing Tan,
Deqian Mao,
Yanyan Liu,
Weidong Li,
Wei Yu,
Junan Yan,
Jianhua Piao,
Chongzheng Guo,
Xiaoli Liu,
Xiaoguang Yang
, Available online , doi: 10.3967/bes2025.017
Objective This study aimed to explore minimum iodine excretion and to build a dietary iodine recommendation for Chinese adults using the obligatory iodine loss hypothesis. Methods Data from 171 Chinese adults (19–21 years old) were collected and analyzed based on three balance studies in Shenzhen, Yinchuan, and Changzhi. The single exponential equation was accordingly used to simulate the trajectory of 24 h urinary iodine excretion as the low iodine experimental diets offered (iodine intake: 11−26 μg·day−1) and to further deduce the dietary reference intakes (DRIs) for iodine, including estimated average requirement (EAR) and recommended nutrient intake (RNI). Results The minimum iodine excretion was estimated as 57, 58, and 51 μg·day−1 in three balance studies, respectively. Moreover, it was further suggested as 57, 58, and 51 μg·day−1 for iodine EAR, and 80, 81, and 71 μg·day−1 for iodine RNI or expressed as 1.42, 1.41, and 1.20 μg·day−1·kg−1 of body weight. Conclusion The iodine DRIs for Chinese adults were established based on the obligatory iodine loss hypothesis, which provides scientific support for the amendment of nutrient requirements.
Yuliang Feng,
Wei Li,
Mingfeng Jiang,
Hongrong Zhong,
Wei Wu,
Lvbo Tian,
Guo Chen,
Zhenhua Chen,
Can Luo,
Rongmei Yuan,
Xingyu Zhou,
Jiandong Li,
Xiaorong Yang,
Ming Pan
, Available online , doi: 10.3967/bes2025.014
Objective This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. Methods Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. Results LASV was detected in the patient’s CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. Conclusion The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
, Available online , doi: 10.3967/bes2025.011
Objective To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. Methods From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. Results Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4°C and 26°C. The relative risk had two peaks at 1.30°C (1.834, 95% CI: 1.204–2.794) and 31.4°C (1.143, 95% CI : 0.901–1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2°C and 18.1°C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. Conclusion The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Mengjiao Xu,
Wen Deng,
Tingting Jiang,
Shiyu Wang,
Ruyu Liu,
Min Chang,
Shuling Wu,
Ge Shen,
Xiaoxue Chen,
Yuanjiao Gao,
Hongxiao Hao,
Leiping Hu,
Lu Zhang,
Yao Lu,
Yao Xie,
Minghui Li,
Wei Yi
, Available online , doi: 10.3967/bes2024.182
Objective : Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. Methods : Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. Results FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. Conclusion To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
, Available online , doi: 10.3967/bes2024.180
Objective To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) against cholestatic liver fibrosis in mice. Methods BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells (HSCs). HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation (BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues. Results BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore, BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell (HSC) activation and collagen fiber formation. Conclusion The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
, Available online , doi: 10.3967/bes2024.177
Objective To explore the correlation between chromosome 8 open reading frame 76 (C8orf76) and cyclin-dependent kinase 4 (CDK4) and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer (CRC). Methods We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4. Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram. Results C8orf76 and CDK4 levels were positively correlated in two independent human CRC cohorts (n = 83 and n = 597). A consistent positive correlation was observed between C8orf76 and CDK4 expression in the CRC cell lines. The nomogram included prognostic genes (C8orf76 and CDK4) and pathological N and M stages. The concordance index (C-index) in our cohort was 0.776, which suggests that the ability of the indicators to predict the overall survival of patients with CRC in our cohort was strong. Conclusions We found that C8orf76 was positively correlated with CDK4 in both the cohorts as well as in CRC cell lines. Therefore, C8orf76 and CDK4 can be used as potential biomarkers to predict the prognosis of CRC.
, Available online , doi: 10.3967/bes2024.175
Objective To evaluate the impact of endometrial polyps (EP) on postoperative pregnancy outcomes in infertile women with endometriosis (EMs). Methods PubMed, Embase, The Cochrane Library, CNKI, VIP, SinoMed, and WanFang Data databases were searched to include clinical studies on the effect of EP on pregnancy outcomes in patients with EMs, published before August 31, 2020. A meta-analysis was performed using Rev Man 5.3 software after two investigators independently screened the literature, extracted information, and evaluated the risk of bias of the included studies. Results The meta-analysis included ten studies (651 and 1040 in the combined EP and uncomplicated EP groups, respectively). The spontaneous pregnancy rate, clinical pregnancy rate, and live birth rate were significantly lower in the group with combined EPs than in the group without combined EPs [Odd’s ratio (OR)=0.63, 95% confidence interval (CI): 0.50-0.80, P = 0.0001; OR = 0.63, 95% CI: 0.48-0.84, P = 0.001; OR = 0.63, 95% CI: 0.42-0.96, P = 0.03], and the rate of embryonic abortion was significantly higher than that in the uncomplicated EP group [OR = 3.10, 95% CI: 1.52-6.32, P = 0.002]. Conclusion EP may adversely affect pregnancy outcomes in patients with infertility and EMs. Even after surgical treatment, EP can still reduce natural pregnancy, clinical pregnancy, and live birth rates in infertile women with EMs and increase the risk of embryo arrest in these women.
, Available online , doi: 10.3967/bes2024.170
Objective Observational studies have shown inconsistent associations of loneliness or social isolation (SI) with ischemic heart disease (IHD), with unknown mediators. Methods Using data from genome-wide association studies of predominantly European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects of loneliness (N = 487,647) and SI traits on IHD (N = 184,305). SI traits included whether individuals lived alone, participated in various types of social activities, and how often they had contact with friends or family (N = 459,830 to 461,369). A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators, including metabolic, behavioral and psychological factors. Results Loneliness increased IHD risk (OR 2.129; 95% confidence interval [CI], 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol and low-density lipoprotein cholesterol. For SI traits, only fewer social activities increased IHD risk (OR, 1.815; 95% CI, 1.189 to 2.772), mediated by hypertension, high-density lipoprotein cholesterol, triglycerides, fasting insulin and smoking cessation. No reverse causality of IHD with loneliness and SI was found. Conclusion These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD, with several mediators as prioritized targets for intervention.
, Available online , doi: 10.3967/bes2024.159
Objective To identify prognostic genes associated with lysosome-dependent cell death (LDCD) in patients with gastric cancer (GC). Methods Differentially expressed genes (DEGs) were identified using The Cancer Genome Atlas - Stomach Adenocarcinoma. Weighted gene co-expression network analysis was performed to identify the key module genes associated with LDCD score. Candidate genes were identified by DEGs and key module genes. Univariate Cox regression analysis, and least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were performed for the selection of prognostic genes, and risk module was established. Subsequently, key cells were identified in the single-cell dataset (GSE183904), and prognostic gene expression was analyzed. Cell proliferation and migration were assessed using the Cell Counting Kit-8 assay and the wound healing assay. Results A total of 4,465 DEGs, 95 candidate genes, and 4 prognostic genes, including C19orf59, BATF2, TNFAIP2, and TNFSF18, were identified in the analysis. Receiver operating characteristic curves indicated the excellent predictive power of the risk model. Three key cell types (B cells, chief cells, and endothelial/pericyte cells) were identified in the GSE183904 dataset. C19orf59 and TNFAIP2 exhibited predominant expression in macrophage species, whereas TNFAIP2 evolved over time in endothelial/pericyte cells and chief cells. Functional experiments confirmed that interfering with C19orf59 inhibited proliferation and migration in GC cells. Conclusion C19orf59, BATF2, TNFAIP2, and TNFSF18 are prognostic genes associated with LDCD in GC. Furthermore, the risk model established in this study showed robust predictive power.
, Available online , doi: 10.3967/bes2024.157
Objective Blood culture remains the gold standard for diagnosing bloodstream infections. Clinical laboratories must ensure the quality of blood culture processes from receipt to obtaining definitive results. We examined laboratory analytical indicators associated with positive blood culture results. Methods Blood cultures collected from Peking Union Medical College Hospital between January 1, 2020, and December 31, 2022, were retrospectively analyzed. The mode of transportation (piping logistics delivery vs. staff), source of blood cultures (outpatient/emergency department vs. inpatient department), rotation of personnel, and time of reception (8:00–19:59 vs. 20:00–07:59) were compared between blood culture-positive and -negative results. Results Between 2020 and 2022, the total positive rate of blood culture was 8.07%. The positive rate of blood cultures in the outpatient/emergency department was significantly higher than that in the inpatient department (12.46% vs. 5.83%; P < 0.0001). The time-to-detection of blood cultures was significantly affected by the delivery mode and personnel rotation. The blood culture positive rate of the total pre-analytical time within 1 h was significantly higher than that within 1-2 h or > 2 h (P < 0.0170). Conclusion Laboratory analytical indicators such as patient source, transportation mode, and personnel rotation significantly impacted the positive detection rate or time of blood culture.
, Available online , doi: 10.3967/bes2024.155
Objective Data on homocysteine (Hcy) status and its determinants are limited among women during pregnancy and postpartum. This cross-sectional study aimed to investigate Hcy levels during pregnancy and postpartum, and to explore the determinants like geographic factor. Methods This study was conducted in women at mid-pregnancy, late-pregnancy and postpartum from southern, central and northern China. Approximately 132 women were included in each stratum by the three phases and regions. Plasma Hcy concentrations were assessed using high-performance liquid chromatography (HPLC), with hyperhomocysteinemia defined as > 10.0 µmol/L. Quantile regression was to estimate medians and interquartile ranges (IQRs), and logistic regression to examine the determinants of hyperhomocysteinemia. Results For 1190 women included, the median (IQR) Hcy concentration was 5.66 (4.62, 7.37) μmol/L. The adjusted median in mid-pregnancy, late-pregnancy and postpartum women was 4.75 (4.13, 5.54), 5.72 (4.81, 6.85) and 7.09 (5.65, 8.75) μmol/L, respectively, showing an increasing trend (P < 0.001). This increasing trend persisted across the three regions. Higher Hcy concentrations were observed in women residing in northern region and those with younger age or lower economic status. A total of 106 (8.9%) women had hyperhomocysteinemia, with a higher prevalence in those residing in northern region (16.0%), or in postpartum women (16.5%). Conclusion Hcy levels, varying with geographic region, maternal age and economic status, are increased from mid-pregnancy to late-pregnancy and postpartum, indicating a need to monitor Hcy levels in pregnant and postpartum women to controlling potential risks related to elevated Hcy levels.
, Available online , doi: 10.3967/bes2024.122
Objective To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization (MR) study. Methods A two-sample MR study was performed using summarized statistics from the genome-wide association studies (GWAS) conducted in reproductive traits, as well as GWAS data on overall psoriasis, psoriatic arthritis (PsA), and psoriasis vulgaris (PV). Besides univariable MR (UVMR), multivariable MR and two-step MR was used to calculate the independent effects and quantify the proportion mediated by education or body mass index (BMI). Results Genetically predicted early age at first sexual intercourse (AFS) led to an increased risk of overall psoriasis [Odds ratio (OR)UVMR: 0.54]; 36.13% of this effect was mediated through BMI and 47.79% through educational attainment. The direct negative casual association between age at first birth (AFB)-PsA was dominant (ORUVMR: 0.76), with 49.61% proportion of the mediation due to BMI. The mediating effect was found for BMI on the AFS-PV relationship, which accounted for 26.27% of the proportion. AFS was inversely associated with the risk of overall psoriasis and PV, with considerable mediation by BMI and educational attainment. Conclusion Early AFB may cause a higher risk of PsA, while the AFS-PsA association was fully mediated by BMI.
, Available online , doi: 10.3967/bes2025.023
, Available online , doi: 10.3967/bes2025.012
Objective Recent studies have overturned the traditional concept of the lung as a "sterile organ" revealing that pulmonary microbiota dysbiosis and abnormal surfactant proteins (SPs) expression are involved in the progression of silicosis. This study aimed to investigate the relationship between abnormal SPs expression and dysbiosis of lung microbiota in silica-induced lung fibrosis, providing insights into mechanisms of silicosis. Methods Lung pathology, SPs expression, and microbiota composition were evaluated in silica-exposed mice. A mouse model of antibiotic-induced microbiota depletion was established, and alveolar structure and SPs expression were assessed. The roles of the lung microbiota and SPs in silicosis progression were further evaluated in mice with antibiotic-induced microbiota depletion, both with and without silica exposure. Results Silica exposure induced lung inflammation and fibrosis, along with increased expression of SP-A expression. Antibiotics (Abx)-induced microbiota depletion elevated SP-A and SP-D expression. Furthermore, silica exposure altered lung microbiota composition, enriching potentially pathogenic taxa. However, antibiotic-induced microbiota depletion prior to silica exposure reduced silica-mediated lung fibrosis and inflammation. Conclusion Lung microbiota is associated with silica-induced lung injury. Overproduction of SP-A and SP-D, induced by Abx-induced microbiota depletion, may enhance the resistance of mouse lung tissue to silica-induced injury.
, Available online , doi: 10.3967/bes2025.006
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