Ru Xia HOU,
Ting Ting YANG,
Jia Jia LIU,
Hao CHEN,
Wen KANG,
Jun Ming LI,
Xiao Tong SHI,
Yi LIANG,
Jun Yu LIU,
Bin ZHAO,
Xiang Yu WANG
, Available online , doi: 10.3967/bes2024.102
Objective This study aimed to explore the spatial heterogeneity and risk factors for dental caries in 12-year-old children in Shanxi province , China. Methods The data encompassed 3,721 participants from the two most recent oral health surveys conducted across 16 districts in Shanxi Province in 2015 and 2018. Eighteen specific variables were analyzed to examine the interplay between socioeconomic factors, medical resources and environmental conditions. The Geo-detector model was employed to assess the impacts and interactions of these ecological factors. Results Socioeconomic factors (Q = 0.30, P < 0.05) exhibited a more substantial impact compared to environmental (Q = 0.19, P < 0.05) and medical resource factors (Q = 0.25, P < 0.05). Notably, the urban population percentage (UPP) demonstrated the most significant explanatory power for the spatial heterogeneity in caries prevalence, as denoted by its highest q-value (q = 0.51, P < 0.05). Additionally, the spatial distribution’s heterogeneity of caries was significantly affected by SO2 concentration (q = 0.39, P < 0.05) and water fluoride levels (q = 0.27, P < 0.05) among environmental factors. Conclusion The prevalence of caries exhibited spatial heterogeneity, escalating from North to South in Shanxi Province, China, influenced by socioeconomic factors, medical resources, and environmental conditions to varying extents.
, Available online , doi: 10.3967/bes2024.103
Objective This study aimed to identify differentially methylated genes (DMGs) associated with natural killer cells in patients with autoimmune thyroiditis (AIT), focusing on the influence of varying water iodine exposure levels. Methods Participants were divided into categories based on median water iodine (MWI) concentrations: iodine-fortified areas (IFA, MWI < 10 µg/L), iodine-adequate areas (IAA, 40 ≤ MWI ≤ 100 µg/L), and iodine-excessive areas (IEA, MWI > 300 µg/L). A total of 176 matched AIT cases and controls were recruited and divided into 89, 40, and 47 pairs for IFA, IAA, and IEA, respectively. DMGs were identified using 850k BeadChip analysis for 10/10 paired samples. Validation of DNA methylation and mRNA expression levels of the DMGs was conducted using MethylTarget™ and QRT-PCR for 176/176 paired samples. Results KLRC1, KLRC3, and SH2D1B were identified as significant DMGs. Validation revealed that KLRC1 was hypomethylated and highly expressed, whereas KLRC3 was hypermethylated and highly expressed in individuals with AIT. Furthermore, KLRC1 was hypomethylated and highly expressed in both IFA and IEA. Conclusion The DNA methylation status of KLRC1 and KLRC3 may play crucial roles in AIT pathogenesis. Additionally, DNA methylation of KLRC1 seems to be influenced by different iodine concentrations in water.
ZENG Wei,
LUO Ming,
DU Pengcheng,
LI Zhenpeng,
PENG Yao,
WANG Mengyu,
ZHAO Wenxuan,
ZHANG Huayao,
LI Yang,
LUO Pengjie,
WU Yannong,
XU Jialiang,
LI Xu,
LU Xin,
KAN Biao
, Available online , doi: 10.3967/bes2024.104
Objectives Our study aimed to conduct genomic characterization of Salmonella strains carrying the blaNDM-1 gene in the intestinal tract of healthy individuals. The objectives were to underscore the importance of genomic surveillance for drug resistance in both commensal and pathogenic bacteria among healthy populations, and to establish protocols for regulating drug resistance plasmids based on the completion of a comprehensive map of drug resistance plasmid genomes. Methods We performed antimicrobial susceptibility testing and employed second- and third-generation sequencing techniques to analyze Salmonella strains harboring the blaNDM-1 gene, to surveil drug-resistant bacteria in the intestines of healthy subjects. Sequence comparison was conducted using both core- and pan-genome approaches. Concurrently, conjugation experiments were carried out to assess the efficiency of plasmid transfer. Results We isolated a carbapenem-resistant Salmonella enterica serovar Typhimurium strain from a healthy food worker in China. This strain harbored an IncHI2/IncHI2A plasmid carrying blaNDM-1 along with multiple antibiotic resistance genes (ARGs). Our findings highlight the potential for asymptomatic carriers to facilitate the transmission of ARGs. Pan-genomic analysis revealed that blaNDM-1-positive plasmids could traverse bacterial species barriers, facilitating cross-host transmission. Conclusions This study marks the first detection of blaNDM-1 in Salmonella strains isolated from healthy individuals. We underscore the risk associated with the transmission of conjugative hybrid plasmids carrying blaNDM-1, which have the potential to be harbored and transmitted among healthy individuals. Enhanced surveillance of drug-resistant pathogens and plasmids in the intestinal microbiota of healthy individuals could provide insights into the risk of ARG transmission and pathways for population-wide dissemination via ARG transfer factors.
, Available online , doi: 10.3967/bes2024.100
Objective To investigate the role of sea-level cerebral blood flow (CBF) in predicting acute mountain sickness (AMS) using three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL). Methods Forty-eight healthy volunteers reached an altitude of 3650 m by air after undergoing a head magnetic resonance imaging (MRI) including 3D-pCASL at sea level. The CBF values of the bilateral anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA), and posterior inferior cerebellar artery (PICA) territories and the laterality index (LI) of CBF were compared between the AMS and non-AMS groups. Statistical analyses were performed to determine the relationship between CBF and AMS, and the predictive performance was assessed using receiver operating characteristic (ROC) curves. Results The mean cortical CBF in women (81.65±2.69 ml/100 g/min) was higher than that in men (74.35±2.12 ml/100 g/min) (P < 0.05). In men, the cortical CBF values in the bilateral ACA, PCA, PICA, and right MCA were higher in patients with AMS than in those without. Cortical CBF in the right PCA best predicted AMS (AUC = 0.818). In women, the LI of CBF in the ACA was different between the AMS and non-AMS groups and predicted AMS with an AUC of 0.753. Conclusion Although the mechanism and prediction of AMS are quite complicated, higher cortical CBF at sea level, especially the CBF of the posterior circulatory system, may be used for prediction in male volunteers using non-invasive 3D-pCASL.
, Available online , doi: 10.3967/bes2024.083
Objective In recent decades, China has implemented a series of policies to address air pollution. We aimed to assess the health effects of these policies on stroke burden attributable to ambient fine particulate matter (PM2.5). Methods Joinpoint regression was applied to explore the temporal tendency of stroke burden based on data from the Global Burden of Disease 2019 study. Results The age-standardized rates of disability-adjusted life year (DALY) for stroke attributable to ambient PM2.5 in China, increased dramatically during 1990−2012, subsequently decreased at an annual percentage change (APC) of −1.98 (95% confidence interval [CI]: −2.26, −1.71) during 2012−2019. For ischemic stroke (IS), the age-standardized DALY rates doubled from 1990 to 2014, and decreased at an APC of −0.83 (95% CI: −1.33, −0.33) during 2014−2019. Intracerebral hemorrhage (ICH) showed a substantial increase in age-standardized DALY rates from 1990 to 2003, followed by declining trends, with APCs of −1.46 (95% CI: −2.74, −0.16) during 2003−2007 and −3.33 (95% CI: −3.61, −3.06) during 2011−2019, respectively. Conversely, the age-standardized DALY rates for subarachnoid hemorrhage (SAH) generally declined during 1990−2019. Conclusion Our results clarified the dynamic changes of the ambient PM2.5−attributable stroke burden in China during 1990−2019, highlighting the health effects of air quality improvement policies.
Kang Lyu,
Shaodong Liu,
Yanli Liu,
Jinlong You,
Xue Wang,
Min Jiang,
Chun Yin,
Desheng Zhang,
Yana Bai,
Minzhen Wang,
Shan Zheng
, Available online , doi: 10.3967/bes2024.113
Objective Previous studies on the association between lipid profiles and chronic kidney disease (CKD) have yielded inconsistent results and no defined thresholds for blood lipids. Methods A prospective cohort study including 32,351 subjects who completed baseline and follow-up surveys over 5 years was conducted. Restricted cubic splines and Cox models were used to examine the association between the lipid profiles and CKD. A regression discontinuity design was used to determine the cutoff value of lipid profiles that was significantly associated with increased the risk of CKD. Results Over a median follow-up time of 2.2 (0.5, 4.2) years, 648 (2.00%) subjects developed CKD. The lipid profiles that were significantly and linearly related to CKD included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C, and TG/HDL-C, whereas low-density lipoprotein cholesterol (LDL-C) and LDL-C/HDL-C were nonlinearly correlated with CKD. TC, TG, TC/HDL-C, and TG/HDL-C showed an upward jump at the cutoff value, increasing the risk of CKD by 0.90%, 1.50%, 2.30%, and 1.60%, respectively, whereas HDL-C showed a downward jump at the cutoff value, reducing this risk by 1.0%. Female and participants with dyslipidemia had a higher risk of CKD, while the cutoff values for the different characteristics of the population were different. Conclusions There was a significant association between lipid profiles and CKD in a prospective cohort from Northwest China, and TG, TC/HDL-C, while TG/HDL-C showed a stronger risk association. The specific cutoff values of lipid profiles may provide a clinical reference for screening or diagnosing CKD risk.
, Available online , doi: 10.3967/bes2024.112
Objective High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. Methods In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. Results Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. Conclusion Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure.
, Available online , doi: 10.3967/bes2024.111
Objective Mitochondrial reactive oxygen species (mtROS) could cause damage to pancreatic β-cells, rendering them susceptible to oxidative damage. Hence, investigating the potential of the mitochondria-targeted antioxidant (Mito-TEMPO) to protect pancreatic β-cells from ferroptosis by mitigating lipid peroxidation becomes crucial. Methods MIN6 cells were cultured in vitro with 100 μmol/L sodium palmitate (SP) to simulate diabetes. FerroOrange was utilized for the detection of Fe2+ fluorescence staining, BODIPY581/591C11 for lipid reactive oxygen species, and MitoSox-Red for mtROS. Alterations in mitophagy levels were assessed through the co-localization of lysosomal and mitochondrial fluorescence. Western blotting was employed to quantify protein levels of Acsl4, GPX4, FSP1, FE, PINK1, Parkin, TOMM20, P62, and LC3. Subsequently, interventions were implemented using Mito-TEMPO and Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) to observe changes in ferroptosis and mitophagy within MIN6 cells. Results We found that SP induced a dose-dependent increase in Fe2+ and lipid ROS in MIN6 cells while decreasing the expression levels of GPX4 and FSP1 proteins. Through bioinformatics analysis, it has been uncovered that mitophagy assumes a crucial role within the ferroptosis pathway associated with diabetes. Additionally, SP decreased the expression of mitophagy-related proteins PINK1 and Parkin, leading to mtROS overproduction. Conversely, Mito-TEMPO effectively eliminated mtROS while activating the mitophagy pathways involving PINK1 and Parkin, thereby reducing the occurrence of ferroptosis in MIN6 cells. CCCP also demonstrated efficacy in reducing ferroptosis in MIN6 cells. Conclusion In summary, Mito-TEMPO proved effective in attenuating mtROS production and initiating mitophagy pathways mediated by PINK1 and Parkin in MIN6 cells. Consequently, this decreased iron overload and lipid peroxidation, ultimately safeguarding the cells from ferroptosis.
, Available online , doi: 10.3967/bes2024.109
Objectives To analyze the epidemiological characteristics and epidemic situation of children with Kashin–Beck disease (KBD) in China, and provide the basis for formulating prevention and control measures. Methods Fixed-point monitoring, moving-point monitoring, and full coverage of monitoring were promoted successively from 1990 to 2023. Some children (7–12 years old) underwent clinical and right-hand X-ray examinations every year. According to the KBD diagnosis criteria, clinical and X-ray assessments were used to confirm the diagnosis. Results In 1990, the national KBD detectable rate was 21.01%. X-ray detection decreased to below 10% in 2003 and below 5% in 2007. Between 2010 and 2018, the prevalence of KBD in children was less than 0.4%, which fluctuated at a low level, and has decreased to 0% since 2019. Spatial epidemiological analysis indicated a spatial clustering of adult patients prevalence rate in the KBD areas. Conclusion The evaluation results of the elimination of KBD in China over the last 2 years showed that all villages in the monitored areas have reached the elimination standard. While the adult KBD patients still need for policy consideration and care.
, Available online , doi: 10.3967/bes2024.110
Objective The DNA double-strand break (DSB) repair system plays a key role in eliminating DNA damage in hematopoietic cells caused by benzene, toluene, ethylbenzene, and xylene (BTEX) compounds, and the polymorphisms of genes controlling this DNA repair system are linked to the different genetic susceptibilities of individuals to respond to the effects of BTEXs. In addition, there is some evidence that BTEX can induce hematological abnormalities through changing the function of micro RNAs regulating the DSB system, but there is no report on the association of their polymorphisms with BTEX-related disorders. This study aimed to explore the relationship between important polymorphisms in miRNA-100 and miRNA-506, two key regulators of the hematopoietic DSB system, including miRNA-100 RS543412 C>T and miRNA-506 RS5905008 A>G, and hematological abnormalities in BTEX-exposed workers. Methods This study included 138 patients who were exposed to BTEX compounds and had one or more abnormalities in their hematological indices and 145 healthy individuals with the same exposure conditions but without any abnormal hematological defects. Polymorphism genotyping was performed using polymerase chain reaction restriction fragment length polymorphism. Results The results revealed that frequency of the T allele as well as the TT and CT genotypes of the miR-100-RS543412C>T single nucleotide polymorphism was significantly lower in patients than in healthy participants (allelic P = 0.005; genotype P = 0.013). Moreover, individuals with TT and CT genotypes in the codominant (CT vs. CC, OR: 0.546, P = 0.034; TT vs. CC, OR: 0.335, P = 0.004), dominant (CT+TT vs. CC, OR: 0.486, P = 0.008), and recessive (TT vs. CC+CT, OR: 0.507, P = 0.038) models had a lower risk of hematological abnormalities. We also observed that the combined heterozygous genotype of the two polymorphisms was significantly different (P = 0.028) between the two groups and was associated with a reduced risk of abnormalities in blood indices (OR: 0.089, P = 0.03). Conclusion These findings suggest that this miR-single nucleotide polymorphism may be a protective non-coding signature underlying the risk of BTEX exposure-related hematological abnormalities. However, this hypothesis requires further investigation.
HU Jing Kun,
TANG Hou Lin,
KANG Wen Ting,
WANG Shu Yu,
XU Jie,
ZHAO De Cai,
HAO Yang,
WANG Xin Lun,
LYU Fan,
ZHANG Guang,
XU Peng
, Available online , doi: 10.3967/bes2024.105
Objective Antiretroviral drugs covered by medical insurance have been gradually used by people living with human immunodeficiency virus (PLWH) in recent years in China. This study aimed to analyze their willingness to pay (WTP) for antiretroviral drugs. Methods A mixed-methods study design involving a cross-sectional survey and in-depth interviews was conducted. A cross-sectional survey was performed to collect data on the general characteristics, economic status, antiretroviral therapy (ART) status, and WTP of PLWH in 18 Chinese cities from August 2022 to February 2023. Multivariate logistic regression was used to analyze the factors associated with WTP. Representatives of PLWH were interviewed via in-depth interviews, and the data were thematically analyzed. Results Among the 941 PLWH, 271 (28.80%) were willing to pay for antiretroviral drugs covered by medical insurance. For basic medical insurance for urban and rural residents, PLWH with the following characteristics were more willing to pay: an educational level of senior high school or technical secondary school, having an undergraduate degree or higher, frequently working away from their hometowns, and homosexual transmission. Off-farm workers and recipients of government medical aid were more unwilling to pay. For basic medical insurance for urban employees, PLWH with the following characteristics were more willing to pay: frequently working away from their hometowns; homosexual transmission; personal annual income ≥100,000 CNY; and adverse events of antiretroviral drugs. The main reasons for PLWH’s WTP for antiretroviral drugs covered by medical insurance were that the drugs had fewer adverse events and were easier to administer. The main reasons for PLWH’s unwillingness to pay were financial difficulties and privacy concerns. Conclusion Nearly one-third of PLWH are willing to pay for antiretroviral drugs covered by medical insurance. In the future, PLWH with a high WTP can be guided to use these drugs.
WANG Li,
WANG Miao Miao,
XU Cheng Dong,
WANG Pei Han,
YOU Mei Ying,
LI Zi Han,
CHEN Xin Mei,
LIU Xin Yu,
LI Xu Dong,
WANG Yuan Yuan,
HU Yue Hua,
YIN Da Peng
, Available online , doi: 10.3967/bes2024.068
Objective The occurrence of chickenpox in rapidly developing areas poses substantial seasonal risk to children. However, certain factors influencing local chickenpox outbreaks have not been studied. Here, we examined the relationship between spatial clustering, heterogeneity of chickenpox outbreaks, and socioeconomic factors in Southern China. Methods We assessed chickenpox outbreak data from Southern China between 2006 and 2021, comprising both relatively fast-growing parts and slower sub-regions, and provides a representative sample of many developing regions. We analyzed the spatial clustering attributes associated with chickenpox outbreaks using Moran’s I and local indicators of spatial association and quantified their socioeconomic determinants using Geodetector q statistics. Results There were significant spatial heterogeneity in the risk of chickenpox outbreaks, with strong correlations between chickenpox risk and various factors, particularly demographics and living environment. Furthermore, interactive effects among specific are factors, such as population density and per capita residential building area, percentage of households with toilets, percentage of rental housing, exhibited q statistics of 0.28, 0.25, and 0.24, respectively. Conclusion This study provides valuable insights into the spatial dynamics of chickenpox outbreaks in rapidly developing regions, revealing the socioeconomic factors affecting disease transmission. These implications extend the formulation of effective public health strategies and interventions to prevent and control chickenpox outbreaks in similar global contexts.
, Available online , doi: 10.3967/bes2024.101
Objective This study aimed to investigate the prevalence of Epstein-Barr virus (EBV) infection in patients with and without cancer. Methods A total of 26,648 participants who underwent whole-blood EBV DNA (WBEBV) assays between January 1, 2020, and August 31, 2023, were included. The chi-square test was used for categorical data analysis, and R software was used to analyze the differences in EBV DNA load levels and the diagnostic capabilities of WBEBV. Results Positive rates were 10.2% and 25.4% for healthy controls (HC) and patients, respectively. The positivity rate for EBV-associated neoplasms (EN) was the highest at 7.53%, followed by leukemia (Le) at 5.49%. The subgroup analysis showed that the positivity rate for abnormal proliferation or hyperplasia (APH) was 31.9%, followed by 30.5% for Le. The WBEBV of patients with transplants (TP), especially living-related transplants (LT), was the highest among all subgroups. WBEBV at diagnosis was used to differentiate between infectious mononucleosis (IM) and chronic active Epstein-Barr virus (CAEBV), with a sensitivity of 67.4% (95% confidence interval [CI]: 57.6–75.8) and specificity of 72% (95% CI: 63.3–79.3). We conclude that the prevalence of EBV infection is low in the healthy population in this region and that a high EBV load at bas`eline is more common in LT, IM, and Lymphocyte Leukemia (LL). Conclusion This study used a large-sample survey to characterize the prevalence of whole-blood EBV levels in various diseases, including the stages and subtypes. The EBV detection rate was higher in patients with malignant disease than in those with benign disease. Our study provides clinicians with baseline information regarding EBV-associated diseases.
, Available online , doi: 10.3967/bes2024.097
Objective Because of the limited number of studies and small sample sizes, whether metabolic syndrome (MS) leads to the occurrence and progression of osteoporosis and the possible underlying mechanisms require further investigation. This study aimed to investigate the association between MS and osteoporosis, along with its influencing factors. Methods This observational cross-sectional study included 139,470 individuals aged ≥ 18 years who underwent health examinations from September 2014 to March 2022. Based on bone mineral density (BMD) screening results, the participants were categorized into a suspected osteoporosis or non-osteoporosis group (control). Participants were further divided into those who met 0 MS criteria, 1 MS criterion, 2 MS criteria, and ≥ 3 MS criteria (MS group). Participants who had undergone health examinations at least twice formed the follow-up cohort; a self-matched analysis was performed on those with follow-up periods ≥ 5 years and unchanged MS grouping. Results Several examination indicators in the suspected osteoporosis group showed statistically significant differences compared with the control group. The proportion of suspected osteoporosis in the MS group was significantly increased compared with that in the 0 MS criteria group (odds ratio [OR]: 1.215, Z = 29.11, P < 0.001, 95% confidence interval: 1.199–1.231). After adjusting for age, sex, smoking, and alcohol consumption, the 2 MS criteria group and MS group still had OR values > 1 (P < 0.001). In the follow-up cohort, the proportion of suspected osteoporosis increased gradually with an increase in the number of MS criteria met at baseline and during each follow-up visit (P < 0.05), with the highest proportion observed in the MS group. However, the proportion of suspected osteoporosis did not increase significantly over time in the different MS groups (P > 0.05). In the follow-up cohort, the proportion of individuals transitioning from normal BMD to suspected osteoporosis was higher in the MS group after ≥ 5 years of follow-up compared with the group meeting 0 MS criteria (0.08% versus 1.15%, χ2 = 10.76, P = 0.001). There was no significant difference in BMD values for the 0 MS criteria group after 5 years (P > 0.05), whereas the other three groups experienced a significant decrease in BMD values after 5 years (P < 0.05). Conclusion MS is an independent risk factor for osteoporosis, and the effect of risk factors related to MS on osteoporosis may exceed that of aging alone. The specific mechanisms warrant further investigation.
, Available online , doi: 10.3967/bes2024.096
Objective To explore the effectiveness of a nutritional intervention in rescuers who screened positive for depression. Methods A randomized controlled trial design was employed. From June to August, 2022, 4,460 rescuers were screened using the Self-Rating Depression Scale (SDS), and 1,615 positive cases were identified. Thirty-one volunteers were recruited and randomly divided into a nutritional intervention group and a control group. The intervention group received health education and nutritional intervention (a compound paste therapy primarily composed of red roses and Seville orange flowers), while the control group received psychological education. SDS scores were assessed before and after the intervention. Results There was a statistically significant decline in SDS scores in the nutritional intervention group after the intervention ( P < 0.05). Furthermore, the SDS scores of the intervention group were significantly lower than those of the control group, both before and after the intervention ( P < 0.05). No severe adverse reactions were observed during safety evaluation. Conclusion The nutritional intervention effectively reduced the depression scores in rescuers. Early nutritional intervention is recommended for rescuers who initially screen positive for depression.
, Available online , doi: 10.3967/bes2024.094
Objective To examine the precise function of influenza A virus target genes (IATGs) in malignancy. Methods Using multi-omics data from the TCGA and TCPA datasets, 33 tumor types were evaluated for IATGs. IATG expression in cancer cells was analyzed using transcriptome analysis. Copy number variation was assessed using GISTICS 2.0. Spearman’s analysis was used to correlate mRNA expression with methylation levels. GSEA was used for the enrichment analysis. Pearson’s correlation analysis was used to examine the association between IATG mRNA expression and IC50. ImmuCellAI algorithm was used to calculate the 24 immune cell lines. Results In 13 solid tumors, IATG mRNA levels were atypically expressed. Except for UCS, UVM, KICH, PCPG, THCA, CHOL, LAMI, and MESO, most cancers contained somatic IATG mutations. The main copy number variants (CNV) types in IATGs are heterozygous amplifications and deletions. In most tumors, IATG mRNA expression is adversely associated with methylation. RT-PCR demonstrated that EGFR, ANXA5, CACNA1C, CD209, UVRAG were upregulated and CLEC4M was downregulated in KIRC cell lines, consistent with the TCGA and GTEx data. Conclusion Genomic changes and clinical characteristics of IATGs were identified, which may offer fresh perspectives linking the influenza A virus to cancer.
LI Ying,
LU Run Ze,
DONG Li Yan,
SUN Li Tao,
ZHANG Zong Yi,
ZHAO Ya Ting,
DUAN Qing,
ZHANG Li Jie,
JIANG Fa Chun,
JIA Jing,
MA Hui Lai
, Available online , doi: 10.3967/bes2024.092
Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome (HFRS) in Qingdao City, China. Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022. Descriptive epidemiologic, seasonal decomposition, spatial autocorrelation, and spatio-temporal cluster analyses were performed. Results A total of 2,220 patients with HFRS were reported over the study period, with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52%. The male:female ratio was 2.8:1. 75.3% of patients were aged between 16 and 60 years old, 75.3% of patients were farmers, and 11.6% had both “three red” and “three pain” symptoms. The HFRS epidemic showed two-peak seasonality: the primary fall-winter peak and the minor spring peak. The HFRS epidemic presented highly spatially heterogeneous, street/township-level hot spots that were mostly distributed in Huangdao, Pingdu, and Jiaozhou. The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak. Conclusion The distribution of HFRS in Qingdao exhibited periodic, seasonal, and regional characteristics, with High spatial clustering heterogeneity. The typical symptoms of “three red” and “three pain” in patients with HFRS were not obvious.
, Available online , doi: 10.3967/bes2024.088
Objectives The combined use of bedaquiline and delamanid (BDQ-DLM) is limited by an increased risk of prolonging the QTc interval. We retrospectively evaluated patients who received DLM/BDQ-containing regimens at a TB-specialized hospital. We aimed to present clinical efficacy and safety data for Chinese patients. Methods This case–control study included patients with multidrug-resistant tuberculosis (MDR-TB) treated with BDQ alone or BDQ plus DLM. Results A total of 96 patients were included in this analysis: 64 in the BDQ group and 32 in the BDQ + DLM group. Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM, 46 patients (71.9%) in the BDQ group and 29 (90.6%) in the BDQ-DLM group achieved sputum culture conversion during treatment. The rate of sputum culture conversion did not differ between the two groups. The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group. The most frequent adverse event was QTc interval prolongation; however, the frequency of adverse events did not differ between the groups. Conclusion In conclusion, our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB. Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.
JIAN Le Yao,
YANG Bo,
MA Ru Lin,
GUO Shu Xia,
HE Jia,
LI Yu,
DING Yu Song,
RUI Dong Sheng,
MAO Yi Dan,
HE Xin,
SUN Xue Ying,
LIAO Sheng Yu,
GUO Heng
, Available online , doi: 10.3967/bes2024.085
Objective This study aimed to explore the relationships between residential greenness and cardiometabolic risk factors among rural adults in Xinjiang and thus provide a theoretical basis and data support for improving the health of residents in this region. Methods We recruited 9,723 adult rural residents from the 51st Regiment of the Third Division of the Xinjiang Production and Construction Corps in September 2016. The normalized difference vegetation index (NDVI) was used to estimate residential greenness. The generalized linear mixed model (GLMM) was used to examine the association between residential greenness and cardiometabolic risk factors. Results Higher residential greenness was associated with lower cardiometabolic risk factor prevalence. After adjustments were made for age, sex, education, and marital status, for each interquartile range (IQR) increase of NDVI500-m, the risk of hypertension was reduced by 10.3% (OR = 0.897, 95% CI = 0.836–0.962), the risk of obesity by 20.5% (OR = 0.795, 95% CI = 0.695–0.910), the risk of type 2 diabetes by 15.1% (OR = 0.849, 95% CI = 0.740–0.974), and the risk of dyslipidemia by 10.5% (OR = 0.895, 95% CI = 0.825–0.971). Risk factor aggregation was reduced by 20.4% (OR = 0.796, 95% CI = 0.716–0.885) for the same. Stratified analysis showed that NDVI500-m was associated more strongly with hypertension, dyslipidemia, and risk factor aggregation among male participants. The association of NDVI500-m with type 2 diabetes was stronger among participants with a higher education level. PM10 and physical activity mediated 1.9%–9.2% of the associations between NDVI500-m and obesity, dyslipidemia, and risk factor aggregation. Conclusion Higher residential greenness has a protective effect against cardiometabolic risk factors among rural residents in Xinjiang. Increasing the area of green space around residences is an effective measure to reduce the burden of cardiometabolic-related diseases among rural residents in Xinjiang.
, Available online , doi: 10.3967/bes2024.081
Objective Microcystin-leucine-arginine (MC-LR) exposure induces lipid metabolism disorders in the liver. Secreted frizzled-related protein 5（SFRP5）is a natural antagonist of winglesstype MMTV integration site family, member 5A (Wnt5a) and an anti-inflammatory adipocytokine. In this study, we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5, which has anti-inflammatory effects, can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase (JNK) pathway. Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders. Subsequently, mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR, and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed. Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner. SFRP5 overexpression in AML12 cells suppressed MC-LR-induced inflammation. Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK. Conclusion MC-LR can induce lipid metabolism disorders in mice, and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.
ZHANG Wei Jia,
ZHAO Jie Rong,
YIN Qi Kai,
LIU Sheng Hui,
WANG Rui Chen,
FU Shi Hong,
LI Fan,
HE Ying,
NIE Kai,
LIANG Guo Dong,
XU Song Tao,
YANG Guang,
WANG Huan Yu
, Available online , doi: 10.3967/bes2024.078
Objective Genotypes (G) 1, 3, and 5 of the Japanese encephalitis virus (JEV) have been isolated in China, but the dominant genotype circulating in Chinese coastal areas remains unknown. We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis (JE) in the coastal provinces of China. Methods In this study, we collected serum specimens from patients with JE in three coastal provinces of China (Guangdong, Zhejiang, and Shandong) from 2018 to 2020 and conducted JEV cross-neutralization tests against G1, 3, and 5. Results Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong (92 patients), Zhejiang (192 patients), and Guangdong (77 patients), China, from 2018 to 2020. Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV. Two cases were confirmed to be infected with G1 JEV, 32 with G3 JEV, and two with G5 JEV. Conclusion G3 was the primary infection genotype among JE cases with a definite infection genotype, and the infection caused by G5 JEV was confirmed serologically in China.
, Available online , doi: 10.3967/bes2024.082
Objective Chlorination is often used to disinfect recreational water in large amusement parks; however, the health hazards of chlorination disinfection by-products (DBPs) to occupational populations are unknown. This study aimed to assess the exposure status of chlorinated DBPs in recreational water and the health risks to employees of large amusement parks. Methods Exposure parameters of employees of three large amusement parks in Shanghai were investigated using a questionnaire. Seven typical chlorinated DBPs in recreational water and spray samples were quantified by gas chromatography, and the health risks to amusement park employees exposed to chlorinated DBPs were evaluated according to the WHO's risk assessment framework. Results Trichloroacetic acid, dibromochloromethane, bromodichloromethane, and dichloroacetic acid were detected predominantly in recreational water. The carcinogenic and non-carcinogenic risks of the five DBPs did not exceed the risk thresholds. In addition, the carcinogenic and non-carcinogenic risks of mixed exposure to DBPs were within the acceptable risk limits. Conclusion Typical DBPs were widely detected in recreational water collected from three large amusement parks in Shanghai; however, the health risks of DBPs and their mixtures were within acceptable limits.
, Available online , doi: 10.3967/bes2024.080
Objective Our study aimed to provide a comprehensive overview of the current status and dynamic trends of the human immunodeficiency virus (HIV) prevalence in Sichuan, the second most heavily affected province in China, and to explore future interventions. Methods The epidemiological, behavioral, and population census data from multiple sources were analyzed to extract inputs for an acquired immunodeficiency syndrome (AIDS) Epidemic Model (AEM). Baseline curves, derived from historical trends in HIV prevalence, were used, and the AEM was employed to examine future intervention scenarios. Results In 2015, the modeled data suggested an adult HIV prevalence of 0.191% in Sichuan, with an estimated 128,766 people living with HIV/AIDS and 16,983 individuals with newly diagnosed infections. Considering current high-risk behaviors, the model predicts an increase in the adult prevalence to 0.306% by 2025, projecting an estimated 212,168 people living with HIV/AIDS and 16,555 individuals with newly diagnosed infections. Conclusion Heterosexual transmission will likely emerge as the primary mode of AIDS transmission in Sichuan. Furthermore, we anticipate a stabilization in the incidence of AIDS with a concurrent increase in prevalence. Implementing comprehensive intervention measures aimed at high-risk groups could effectively alleviate the spread of AIDS in Sichuan.
, Available online , doi: 10.3967/bes2024.079
Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease (NAFLD). Methods Literature from Web of Science, PubMed, and Embase between January 1980 and September 2022 was systematically searched. Meta-analyses of the genetic variants were conducted using at least five data sources. The epidemiologic credibility of the significant associations was graded using the Venice criteria. Results Based on literature screening, 399 eligible studies were included, comprising 381 candidate gene association, 16 genome-wide association, and 2 whole-exome sequencing studies. We identified 465 genetic variants in 173 genes in candidate gene association studies, and 25 genetic variants in 17 genes were included in the meta-analysis. The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD, with cumulative epidemiological evidence of an association graded as strong for two variants in two genes (HFE, TNF), moderate for four variants in three genes (TM6SF2, GCKR, and ADIPOQ), and weak for five variants in five genes (MBOAT7, PEMT, PNPLA3, LEPR, and MTHFR). Conclusions This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD, which may help understand the genetic architecture of NAFLD risk.
, Available online , doi: 10.3967/bes2024.114
SONG Le Quan,
HE Zhi Wei,
PAN Jun Miao,
DONG Ji,
WANG Hao Yu,
ZHANG Jing,
YAO Bin Wei,
XU Xin Ping,
WANG Hui,
ZHAO Li,
PENG Rui Yun
, Available online , doi: 10.3967/bes2024.099
, Available online , doi: 10.3967/bes2024.098
ZHANG Dong Dong,
CHEN Wei Ling,
GU Min Qi,
LI Xi,
WU Yu Ying,
FU Xue Ru,
TANG Ping,
HU Fu Lan,
LI Jing,
SUN Xi Zhuo,
HU Dong Sheng,
ZHANG Ming
, Available online , doi: 10.3967/bes2024.093
, Available online , doi: 10.3967/bes2024.091
, Available online , doi: 10.3967/bes2024.086
, Available online , doi: 10.3967/bes2024.084
Despite well-known limitations, mice remain useful as model animals to study tuberculosis (TB) pathogenesis, the basic immune response, the extent of lung pathology as well as efficacy of new drugs against Mycobacterium tuberculosis[1,2]. There are four routes of tuberculosis infection in mice: aerosol generation and exposition, intravenous injection, intranasal administration, and subcutaneous administration[3], and the first two are the most commonly used. The low-dose aerosol model was found to best fit the dissemination of TB cases in the community while intravenous infection is useful to study strain virulence[4]. Intra-nasal and intra-tracheal inoculation techniques have a high degree of variability in the delivery of bacilli into the alveoli and the generation of an aerosol cloud of very small droplet nuclei containing the bacilli was shown to be the most reproducible method[1]. In the case of the intravenous tail injection, the administered doses are higher compared to the aerosol route. The intravenous infection leads to the initial infection established in the lungs followed by the dissemination of the bacteria through the body of the animal. The genetic background of mice plays an important role in susceptibility to the infection and further progression to disease. Intravenous infection can lead to a rapid development of disease and an increased animal lethality after 28 days of the infection but this concerns susceptible C3H/HeJ mice lineage and not resistant C57BL/6 lineage[5]. The latter is resistant to infection and develops severe pulmonary damage after a long period since intravenous infection, around 200 days. Therefore, this design is relevant to study the virulence and is appropriate for observation of the long-term therapy of multi-drug resistant (MDR) M. tuberculosis infection.
, Available online , doi: 10.3967/bes2024.095
Melanocytes derived from neural crest cells harbor the BRAFV600E mutation, which is the predominant driver of nevus formation in humans. This mutation leads to malignant cell proliferation and subsequent cell cycle arrest, culminating in oncogene-induced senescence and nevus development. Nevertheless, emerging evidence has highlighted the heterogeneity of cellular senescence markers in BRAFV600E-induced senescent melanocytes. Moreover, the capacity of melanocytes within nevi to regain their proliferative ability raises questions about the molecular mechanisms by which BRAFV600E, via the mitogen-activated protein kinase signaling pathway, triggers nevus formation. This study provides an overview and discussion of the molecular mechanisms underpinning BRAFV600E-induced melanocyte nevus formation and the relevant animal models employed for their elucidation. It also highlights the significance of elucidating dynamic changes in cytoplasmic and nuclear substrates that interact with phosphorylated extracellular signal-regulated protein kinases 1 and 2 and underscores the value of using targeted BRAFV600E animal models created through gene editing technologies.
, Available online , doi: 10.3967/bes2024.090
Cerebral hemorrhage, the second most prevalent subtype of stroke, exacerbates blood-brain barrier (BBB) disruption, leading to vasogenic edema, plasma protein extravasation, and infiltration of neurotoxic substances. The brain's clearance capacity plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery post-hemorrhage. This study aims to investigate the impact of circadian rhythms on BBB function, neuronal damage, and clearance capabilities. A Neurovascular Unit (NVU) model was established through a four-cell co-culture of neurons, astrocytes, microglia, and brain microvascular endothelial cells (BMECs). Circadian rhythms were found to play a pivotal role in preserving BBB integrity, reducing oxidative stress-induced neuronal damage and apoptosis, and enhancing the phagocytic capabilities of microglial cells. The study underscores the potential circadian modulation of BBB integrity through key protein expressions, including Occludin, melatonin receptor 1A (MTNR1A), Aquaporin-4 (AQP4), and Low-density lipoprotein receptor-related protein 1 (LRP1). This comprehensive exploration of the NVU under circadian influence provides valuable insights into enhancing brain clearance abilities post-cerebral hemorrhage. The study emphasizes the significance of circadian regulation in neurological disorders, proposing potential therapeutic interventions and highlighting the importance of maintaining circadian rhythms for optimal brain health. The findings lay the foundation for future research targeting circadian-influenced mechanisms within the NVU to improve outcomes for patients post-cerebral hemorrhage.
, Available online , doi: 10.3967/bes2024.077
Objective A high sodium (HS) diet is believed to affect bone metabolism processes. Clarifying its impact on osseointegration of titanium (Ti) implants holds significant implications for postoperative dietary management of implanted patients. Methods This investigation probed the impact of sodium ions (Na+) on neovascularization and osteogenesis around Ti implants in vivo, utilizing micro-computed tomography, hematoxylin and eosin staining, and immunohistochemical analyses. Concurrently, in vitro experiments assessed the effects of varied Na+ concentrations and exposure durations on human umbilical vein endothelial cells (HUVECs) and MC3T3-E1 cells. Results In vivo, increased dietary sodium (0.8%-6%) led to a substantial decline in CD34 positive HUVECs and new bone formation around Ti implants, alongside an increase in inflammatory cells. In vitro, an increase in Na+ concentration (140 mmol/L–150 mmol/L) adversely affected the proliferation, angiogenesis, and migration of HUVECs, especially with prolonged exposure. While MC3T3-E1 cells initially exhibited less susceptibility to high Na+ concentrations compared to HUVECs during short-term exposure, prolonged exposure to a HS environment progressively diminished their proliferation, differentiation, and osteogenic capabilities. Conclusion These findings suggest that HS diet had a negative effect on the early osseointegration of Ti implants by interfering with the process of postoperative vascularized bone regeneration.
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