Association between body mass index and semen quality: a systematic review and meta-analysis.

The continuous decline of human semen quality during the past decades has drawn much concern globally. Previous studies have suggested a link between abnormal BMI and semen quality decline, but the results remain inconsistent. This systematic review and meta-analysis aimed to evaluate the association between body mass index (BMI) and semen quality. We searched PubMed, Embase, and Web of Science for eligible studies from inception to April 17, 2022. We considered men with BMI < 25.0 kg/m2 as the reference and calculated the pooled weighted mean difference of men with overweight (BMI 25.0-29.9 kg/m2), obesity (BMI ≥ 30.0 kg/m2), class I obesity (BMI 30.0-34.9 kg/m2), and class II/III obesity (BMI ≥ 35.0 kg/m2). A total of 5070 articles were identified, of which 50 studies were included (71,337 subjects). Compared with men with BMI < 25.0 kg/m2, men with obesity had an average reduction of 0.24 ml in semen volume, 19.56 × 106 in total sperm number, 2.21% in total motility, 5.95% in progressive motility, and 1.08% in normal forms, respectively, while men with overweight had an average reduction of 0.08 ml in semen volume and 2.91% in progressive motility, respectively. The reduction of semen quality was more pronounced among men with obesity than that among men with overweight. Moreover, significant reductions in semen quality were identified in men with different classes of obesity, which were more pronounced in men with class II/III obesity than that in men with class I obesity. Across men from the general population, infertile or subfertile men, and suspiciously subfertile men, we identified significant semen quality reductions in men with obesity/overweight. In conclusion, obesity and overweight were significantly associated with semen quality reductions, suggesting that maintaining normal weight may help prevent semen quality decline.

Ozone, Heat Wave, and Cardiovascular Disease Mortality: A Population-Based Case-Crossover Study.

A case-crossover study among 511,767 cardiovascular disease (CVD) deaths in Jiangsu province, China, during 2015-2021 was conducted to assess the association of exposure to ambient ozone (O3) and heat wave with CVD mortality and explore their possible interactions. Heat wave was defined as extreme high temperature for at least two consecutive days. Grid-level heat waves were defined by multiple combinations of apparent temperature thresholds and durations. Residential O3 and heat wave exposures were assessed using grid data sets (spatial resolution: 1 km × 1 km for O3; 0.0625° × 0.0625° for heat wave). Conditional logistic regression models were applied for exposure-response analyses and evaluation of additive interactions. Under different heat wave definitions, the odds ratios (ORs) of CVD mortality associated with medium-level and high-level O3 exposures ranged from 1.029 to 1.107 compared with low-level O3, while the ORs for heat wave exposure ranged from 1.14 to 1.65. Significant synergistic effects on CVD mortality were observed for the O3 and heat wave exposures, which were generally greater with higher levels of the O3 exposure, higher temperature thresholds, and longer durations of heat wave exposure. Up to 5.8% of the CVD deaths were attributable to O3 and heat wave. Women and older adults were more vulnerable to the exposure to O3 and heat wave exposure. Exposure to both O3 and heat wave was significantly associated with an increased odds of CVD mortality, and O3 and heat wave can interact synergistically to trigger CVD deaths.

Long-term exposure to ambient fine particulate matter constituents and mortality from total and site-specific gastrointestinal cancer.

BACKGROUND: Ambient fine particulate matter (PM2.5) exposure has been associated with an increased risk of gastrointestinal cancer mortality, but the attributable constituents remain unclear. OBJECTIVES: To investigate the association of long-term exposure to PM2.5 constituents with total and site-specific gastrointestinal cancer mortality using a difference-in-differences approach in Jiangsu province, China during 2015-2020. METHODS: We split Jiangsu into 53 spatial units and computed their yearly death number of total gastrointestinal, esophagus, stomach, colorectum, liver, and pancreas cancer. Utilizing a high-quality grid dataset on PM2.5 constituents, we estimated 10-year population-weighted exposure to black carbon (BC), organic carbon (OC), sulfate, nitrate, ammonium, and chloride in each spatial unit. The effect of constituents on gastrointestinal cancer mortality was assessed by controlling time trends, spatial differences, gross domestic product (GDP), and seasonal temperatures. RESULTS: Overall, 524,019 gastrointestinal cancer deaths were ascertained in 84.77 million population. Each interquartile range increment of BC (0.46 µg/m3), OC (4.56 µg/m3), and nitrate (1.41 µg/m3) was significantly associated with a 27%, 26%, and 34% increased risk of total gastrointestinal cancer mortality, respectively, and these associations remained significant in PM2.5-adjusted models and constituent-residual models. We also identified robust associations of BC, OC, and nitrate exposures with site-specific gastrointestinal cancer mortality. The mortality risk generally displayed increased trends across the total exposure range and rose steeper at higher levels. We did not identify robust associations for sulfate, ammonium, or chlorine exposure. Higher mortality risk ascribed to constituent exposures was identified in total gastrointestinal and liver cancer among women, stomach cancer among men, and total gastrointestinal and stomach cancer among low-GDP regions. CONCLUSIONS: This study offers consistent evidence that long-term exposure to PM2.5-bound BC, OC, and nitrate is associated with total and site-specific gastrointestinal cancer mortality, indicating that these constituents need to be controlled to mitigate the adverse effect of PM2.5 on gastrointestinal cancer mortality.

Extreme temperature events and dementia mortality in Chinese adults: a population-based, case-crossover study.

BACKGROUND: The effect of exposure to extreme temperature events (ETEs) on dementia mortality remains largely unknown. We aimed to quantify the association of ETE exposure with dementia mortality. METHODS: We conducted a population-based, case-crossover study among 57 791 dementia deaths in Jiangsu province, China, during 2015-20. Daily mean temperatures were extracted from a validated grid dataset at each subject's residential address, and grid-specific exposures to heat wave and cold spell were assessed with a combination of their intensity and duration. We applied conditional logistic regression models to investigate cumulative and lag effects for ETE exposures. RESULTS: Exposure to ETE with each of all 24 definitions was associated with an increased odds of dementia mortality, which was higher when exposed to heat wave. Exposure to heat wave (daily mean temperature ≥95th percentile, duration ≥3 days (d); P95_3d) and cold spell (≤5th percentile, duration ≥3 d; P5_3d) was associated with a 75% (95% CI: 61%, 90%) and 30% (19%, 43%) increase in odds of dementia mortality, respectively. Definitions with higher intensity were generally associated with a higher odds of dementia mortality. We estimated that 6.14% of dementia deaths were attributable to exposure to heat wave (P90_2d) and cold spell (P10_2d). No effect modifications were observed by sex or age, except that the association for heat wave was stronger among women. CONCLUSIONS: Exposure to both heat wave and cold spell was associated with an increased odds of dementia mortality. Our findings highlight that reducing individual ETE exposures may be helpful in preventing deaths from dementia, especially among women in summer.

Association of short-term exposure to ambient fine particulate matter and ozone with outpatient visits for anxiety disorders: A hospital-based case-crossover study in South China.

BACKGROUND: The short-term adverse effects of ambient fine particulate matter (PM2.5) and ozone (O3) on anxiety disorders (ADs) remained inconclusive. METHODS: We applied an individual-level time-stratified case-crossover study, which including 126,112 outpatient visits for ADs during 2019-2021 in Guangdong province, China, to investigate the association of short-term exposure to PM2.5 and O3 with outpatient visits for ADs, and estimate excess outpatient visits in South China. Daily residential air pollutant exposure assessments were performed by extracting grid data (spatial resolution: 1 km × 1 km) from validated datasets. We employed the conditional logistic regression model to quantify the associations and excess outpatient visits. RESULTS: The results of the single-pollutant models showed that each 10 µg/m3 increase of PM2.5 and O3 exposures was significantly associated with a 3.14 % (95 % confidence interval: 2.47 %, 3.81 %) and 0.88 % (0.49 %, 1.26 %) increase in odds of outpatient visits for ADs, respectively. These associations remained robust in 2-pollutant models. The proportion of outpatient visits attributable to PM2.5 and O3 exposures was up to 7.20 % and 8.93 %, respectively. Older adults appeared to be more susceptible to PM2.5 exposure, especially in cool season, and subjects with recurrent outpatient visits were more susceptible to O3 exposure. LIMITATION: As our study subjects were from one single hospital in China, it should be cautious when generalizing our findings to other regions. CONCLUSION: Short-term exposure to ambient PM2.5 and O3 was significantly associated with a higher odds of outpatient visits for ADs, which can contribute to considerable excess outpatient visits.

Short-term exposure to ambient fine particulate matter constituents and myocardial infarction mortality.

Short-term ambient fine particulate matter (PM2.5) exposure has been related to an increased risk of myocardial infarction (MI) death, but which PM2.5 constituents are associated with MI death and to what extent remain unclear. We aimed to explore the associations of short-term exposure to PM2.5 constituents with MI death and evaluate excess mortality. We conducted a time-stratified case-crossover study on 237,492 MI decedents in Jiangsu province, China during 2015-2021. Utilizing a validated PM2.5 constituents grid dataset at 1 km spatial resolution, we estimated black carbon (BC), organic carbon (OC), sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and chloride (Cl-) exposure by extracting daily concentrations grounding on the home address of each subject. We employed conditional logistic regression models to evaluate the exposure-response relationship between PM2.5 constituents and MI death. Overall, per interquartile range (IQR) increase of BC (lag 06-day; IQR: 1.75 µg/m3) and SO42- (lag 04-day; IQR: 5.06 µg/m3) exposures were significantly associated with a 3.91% and 2.94% increase in odds of MI death, respectively, and no significant departure from linearity was identified in the exposure-response curves for BC and SO42-. If BC and SO42- exposures were reduced to theoretical minimal risk exposure concentration (0.89 µg/m3 and 1.51 µg/m3), an estimate of 4.55% and 4.80% MI deaths would be avoided, respectively. We did not find robust associations of OC, NO3-, NH4+, and Cl- exposures with MI death. Individuals aged ≥80 years were more vulnerable to PM2.5 constituent exposures in MI death (p for difference <0.05). In conclusion, short-term exposure to PM2.5-bound BC and SO42- was significantly associated with increased odds of MI death and resulted in extensive excess mortality, notably in older adults. Our findings emphasized the necessity of reducing toxic PM2.5 constituent exposures to prevent deaths from MI and warranted further studies on the relative contribution of specific constituents.

Solid-Phase Polymerization Using Anion-Exchange Resin Can Almost Completely Crosslink Hemoglobin to Prepare Hemoglobin-Based Oxygen Carriers.

Introduction: A limitation of hemoglobin-based oxygen carriers (HBOCs) as oxygen therapeutics is unpolymerized hemoglobin, which induces vasoconstriction leading to hypertension. The removal of unpolymerized hemoglobin from polymerized hemoglobin (PolyHb) is complex, expensive, and time-consuming. Methods: Herein, we developed a method to completely polymerize hemoglobin almost without unpolymerized hemoglobin. Hemoglobin was adsorbed on the anion-exchange resin Q Sepharose Fast Flow or DEAE Sepharose Fast Flow, and acetal, a crosslinker prepared from glutaraldehyde and ethylene glycol, was employed to polymerize the hemoglobin. The polymerization conditions, including reaction time, pH, resin type, and molar ratios of glutaraldehyde to ethylene glycol and hemoglobin to acetal, were optimized. The blood pressure and blood gas of mice injected with PolyHb were monitored as well. Results: The optimal polymerization condition of PolyHb was when the molar ratio of glutaraldehyde to ethylene glycol was 1:20, and the molar ratio of 10 mg/mL hemoglobin adsorbed on anion-exchange resin to glutaraldehyde was 1:300 for 60 min. Under optimized reactive conditions, hemoglobin was almost completely polymerized, with <1% hemoglobin remaining unpolymerized, and the molecular weight of PolyHb was more centrally distributed. Furthermore, hypertension was not induced in mice by PolyHb, and there were also no pathological changes observed in arterial oxygen, blood gas, electrolytes, and some metabolic indicators. Conclusion: The findings of this study indicate that the use of solid-phase polymerization and acetal is a highly effective and innovative approach to HBOCs, resulting in the almost completely polymerized hemoglobin. These results offer promising implications for the development of new methods for preparing HBOCs.

Association between exposure to ambient air pollution and semen quality: A systematic review and meta-analysis.

BACKGROUND: Accumulating evidence has linked exposure to ambient air pollution to a reduction in semen quality; however, the exposure-response associations are yet to be synthesized. OBJECTIVE: To summarize the exposure-response associations between air pollution and semen quality. METHODS: We systematically searched PubMed, Embase, and Web of Science for relevant studies published before April 20, 2022. Studies investigating the exposure-response association of PM2.5, PM10, SO2, NO2, CO, and O3 with semen quality written in English were included. Semen quality parameters included semen volume, sperm concentration, total sperm number, total motility, progressive motility, and normal forms. Random-effects and fixed-effects models were performed to synthesize associations in the meta-analysis. RESULTS: The search returned 850 studies, 11 of which were eligible for meta-analysis. Each 10 µg/m3 increase of exposure to PM10 and SO2 was respectively associated with a 2.18 % (95 % confidence interval [CI]: 0.10 %-4.21 %) and 8.61 % (1.00 %-15.63 %) reduction in sperm concentration, and a 2.76 % (0.10 %-5.35 %) and 9.52 % (5.82 %-13.93 %) reduction in total sperm number. Each 10 µg/m3 increase of exposure to PM2.5 and PM10 was respectively associated with a 1.06 % (95 % CI: 0.31 %-1.82 %) and 0.75 % (0.43 %-1.08 %) reduction in total motility, and a 0.55 % (0.09 %-1.01 %) and 0.31 % (0.06 %-0.56 %) reduction in progressive motility. No association was observed for PM2.5 or PM10 with semen volume; PM2.5, NO2, CO, or O3 with sperm concentration or total sperm number; and gaseous air pollutants with total or progressive motility. The association between air pollution and normal forms was not summarized due to insufficient number of studies. No significant publication bias was detected. CONCLUSIONS: Exposure to ambient PM2.5, PM10, and SO2 was inversely associated with sperm concentration, total sperm number, total motility, and/or progressive motility. Our findings add to the evidence that air pollution may lead to adverse effects on male reproductive system and suggest that reducing exposure to air pollution may help maintain better semen quality.

rs144012689 is a highly specific representative marker of HLA-B*15:02 in the Chinese population.

Objective: To develop an accurate and rapid real-time PCR technique for HLA-B*15:02 genotyping and investigate HLA-B*15:02 allele frequency in four ethnic populations in China. Materials & methods: Based on the highly specific representative markers, a real-time PCR assay was developed for HLA-B*15:02 genotyping, and HLA-B*15:02 allele frequencies were screened in four ethnic populations of China. Sequence-based typing was used to validate the accuracy of the assay. Results: The sensitivity and specificity of the assay were 100%, and the detection limit was 0.2 ng. The frequency of HLA-B*15:02 alleles distributed in the Bouyei population was significantly higher than in the Han group (p < 0.01). Neither the Tibetan nor the Uyghur population carried the HLA-B*15:02 haplotype. Conclusion: The authors developed an accurate HLA-B*15:02 genotyping method for evaluating the risk of adverse drug reactions induced by carbamazepine in various ethnic populations in China.

MiR-1254 and MEGF6 regulates oxaliplatin resistance in human colorectal cancer cells.

Colorectal cancer (CRC) remains one of the deadliest diseases in the whole world. Cancer recurrence and chemotherapeutic drug resistance limit the overall survival rate of patients with CRC. This study aimed to discover the latent miRNAs and genes associated with oxaliplatin resistance in CRC cells. The study found that miR-1254 is upregulated in oxaliplatin-resistant CRC cell line HCT116-R compared with its parental cell line HCT116 by transcriptome sequencing and small RNA sequencing. Meanwhile, MEGF6 (multiple EGF-like domains 6) was downregulated in HCT116-R cells. Transient transfection of miR-1254 mimics significantly reduced cell apoptosis, increased HCT116 tolerance to oxaliplatin, and enhanced MEGF6 expression. Furthermore, transfection of miR-1254 inhibitor increased apoptosis, decreased HCT116-R tolerance to oxaliplatin, and reduced MEGF6 expression. In addition, transient transfection of SiMEGF6 enhanced HCT116 cell resistance to oxaliplatin and reduced cell apoptosis. In summary, MEGF6 is a latent functional target of miR-1254 in regulating oxaliplatin resistance and apoptosis in human CRC cells, suggesting a potential therapeutic target for CRC.

KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cells.

Paclitaxel (PTX), a tubulin-binding agent, is widely used and has shown good efficacy in the initial period of treatment for non-small cell lung cancer (NSCLC). However, the relatively rapid acquisition of resistance to PTX treatments that is observed in virtually all cases significantly limits its utility and remains a substantial challenge to the clinical management of NSCLC. The aim of this study was to identify candidate genes and mechanisms that might mediate acquired paclitaxel resistance. In this work, we established paclitaxel-resistant cells (A549-T) from parental cell lines by step-dose selection in vitro. Using methylation chip analysis and transcriptome sequencing, 43,426 differentially methylated genes and 2,870 differentially expressed genes are identified. Six genes (KANK1, ALDH3A1, GALNT14, PIK3R3, LRG1, WEE2), which may be related to paclitaxel resistance in lung adenocarcinoma, were identified. Among these genes, KANK1 exhibited significant differences in methylation and expression between cell lines. Since KANK1 plays an important role in the development of renal cancer and gastric cancer, we hypothesised that it may also play a role in acquired resistance in lung adenocarcinoma. Transient transfection of SiKANK1 significantly reduced the expression of KANK1, reducing apoptosis, increasing cell migration, and enhancing the tolerance of A549 cells to paclitaxel. KANK1 acts as a tumour suppressor gene, mediating the resistance of lung adenocarcinoma A549 to paclitaxel. The reduction of KANK1 expression can increase the paclitaxel resistance of non-small cell lung cancer and increase the difficulty of clinical treatment.