Background Pyrethroid pesticides (PYRs) can cross the placental barrier to cause intrauterine fetal exposure, which may lead to developmental immunotoxicity (DIT). However, the specific effect of maternal PYR exposure during pregnancy on the cellular immune function of 1-year-old children remains unclear. Objective To explore the effect of PYRs exposure throughout the entire pregnancy on peripheral blood lymphocytes in 1-year-old children and potential sensitive window period of PYRs exposure. Methods A birth cohort was established by enrolling pregnant women in their first trimester and following them and their infants until one year of age. Ultra-high performance liquid chromatography-tandem mass spectrometry was used to detect the levels of PYRs metabolites, including 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), and cis-3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane carboxylic acid (cis-DBCA), in the urine of pregnant women during the first trimester (gestational weeks 6-12), the second trimester (gestational weeks 21-24), and the third trimester (gestational weeks 33-36). Peripheral blood leukocyte and lymphocyte counts were measured in children at 12 months of age using the Coulter principle combined with flow cytometry. Exposure levels of PYRs metabolites in each trimester were divided into low, moderate, and high exposure groups based on the 25th (P₂₅) and 75th (P₇₅) percentiles. Meanwhile, participants were classified as having repeated high or low exposure if their metabolite levels were > P₇₅ or <P₂₅ in at least two trimesters, respectively, while all others were categorized as having repeated moderate exposure. Generalized linear models were used to analyze the associations between trimester-specific and repeated PYRs metabolite exposure levels and the peripheral blood white blood cell (WBC) and lymphocyte counts in children aged 1 year. Results A total of 336 mother-child pairs were included in this study. For the pregnant women, the total detection rates of maternal urinary 3PBA, 4F3PBA, and cis-DBCA across the three trimesters of pregnancy were 80.5%, 100.0%, and 81.3%, respectively; and median creatinine-corrected concentrations were 0.24, 0.36, and 0.42 μg·g⁻¹, respectively. In children aged 1 year, the mean WBC and lymphocyte counts in peripheral blood were (8.9±2.0)×10⁹·L⁻¹ and (5.7±1.6)×10⁹·L⁻¹, respectively. The results of the generalized linear model analysis indicated that compared to the low exposure group, the high cis-DBCA exposure group during the third trimester of pregnancy had significantly lower peripheral blood WBC count (β=−0.87, 95%CI: −1.51, −0.23) and lymphocyte count (β=−0.64, 95%CI: −1.15, −0.13); and the repeated high-exposure group of cis-DBCA had significantly lower peripheral blood WBC count (β=−1.34, 95%CI: −2.34, −0.34) and lymphocyte count (β=−0.80, 95%CI: −1.60, −0.01) than the repeated low exposure group. Similarly, the repeated moderate-exposure group of cis-DBCA had a significantly lower peripheral blood WBC count (β=−0.83, 95%CI: −1.59, −0.07) than the repeated low exposure group. Conclusion High maternal exposure to PYRs with cis-DBCA as the major metabolite exposure is associated with decreased peripheral leukocyte and lymphocyte counts in children aged 1 year, and repeated high-level exposure throughout gestation appears to exacerbate DIT in offspring. The third trimester of pregnancy maybe a sensitive window for children's DIT induced by exposure to PYRs during pregnancy.

CRISPR-Cas-based biosensing systems have become important platforms for rapid nucleic acid detection because of their programmable sequence recognition and high specificity. In many diagnostic workflows, the CRISPR reaction is coupled with polymerase chain reaction or isothermal pre-amplification to enrich low-abundance targets before readout. This design improves sensitivity, but it also introduces additional primers and enzymes, requirements for temperature control and reaction compatibility, and a higher demand for contamination management. These factors make the whole assay less convenient for integrated and field-deployable point-of-care testing. Developing pre-amplification-free CRISPR assays is therefore not simply a pursuit of shorter protocols, but a way to simplify molecular diagnosis at the system level, especially in settings where rapid decisions, closed workflows, and minimal manual operation are required. Microfluidic devices provide an important engineering route for this purpose. Their small reaction volumes, precise fluid manipulation, high-throughput partitioning, and compatibility with portable readout make it possible to integrate target confinement, reaction control, signal acquisition, and quantitative analysis on a chip. Droplet microfluidics and microwell arrays can divide a sample into large numbers of independent microreactors, enabling digital counting of rare recognition events. Continuous-flow, centrifugal, and paper-based microfluidic formats further provide options for automated operation, low-cost fabrication, and on-site use. In this context, microfluidics is not only a signal-enhancement method, but also a platform that connects CRISPR molecular recognition with practical assay implementation. This review summarizes recent progress in microfluidic-based pre-amplification-free CRISPR-Cas biosensing for rapid detection. We focus on four related technical directions. crRNA engineering, including spacer-length tuning, multi-crRNA design, chemical modification, and allosteric regulation, can improve recognition kinetics, nuclease stability, and mismatch discrimination. Digital microfluidic detection based on droplets or microwell arrays converts single-molecule recognition events into countable positive partitions, thereby improving quantitative capability without target pre-amplification. Physical signal transduction interfaces couple CRISPR activity to electrochemical, electrochemiluminescent, fluorescent, or surface-enhanced Raman scattering readouts, making weak molecular signals easier to detect with portable instruments. On-chip cascade signal amplification strategies further enhance output intensity through enzymatic reactions, DNA circuits, nanomaterials, or cross-domain amplification modules while avoiding direct amplification of the target nucleic acid. Together, these strategies show that the performance of a pre-amplification-free assay depends not only on biochemical recognition, but also on how the reaction is confined, amplified, transduced, and operated. In addition to describing these mechanisms, this review compares different strategies in terms of sensitivity improvement, operational complexity, cost, and suitability for point-of-care testing. Representative applications in food authenticity identification and rapid pathogen screening are also discussed to illustrate how these platforms perform in practical scenarios. Finally, we analyze the remaining challenges, including the detection of low-abundance targets in complex matrices, on-chip sample preparation, device-to-device reproducibility, long-term reagent storage, and standardization. Future development will likely depend on tighter integration of sample processing, CRISPR reaction, signal readout, and data interpretation, ultimately moving pre-amplification-free CRISPR diagnostics toward automated and user-friendly sample-to-answer systems.

Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.

Obesity represents a complex, heritable condition shaped by interactions among genetic, epigenetic, metagenomic, and environmental factors. Nevertheless, the mechanistic contributions of genetic variation and epigenetic regulation to obesity pathogenesis remain incompletely elucidated. Advances in molecular profiling technologies have enabled the identification of numerous biomarkers associated with childhood obesity phenotypes. These discoveries facilitate understanding of obesity etiology and its links to chronic diseases. This review synthesizes current research on genomic and epigenomic biomarkers influencing childhood obesity susceptibility, advances our comprehension of etiological heterogeneity and intervention strategies, and offers conceptual frameworks for precision prevention based on epigenetic mechanisms.

AIM To investigate the effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage in rats with opioid-induced constipation(OIC)of Spleen-Kidney Yang Deficiency Syndrome.METHODS In contrast to the 10 rats of the blank group,the 50 rats of the modeling group were induced into models of OIC of Spleen-Kidney Yang Deficiency Pattern by 7 days consecutive administration of both subcutaneous loperamide injection and alternating gavage of activated carbon ice water and vinegar.Following successful modeling,rats were randomly allocated into the model group,the mosapride citrate tablet group(1.35 mg/kg),and the high-dose,medium-dose,and low-dose Yunpi Tongchang Formula groups(15.12,7.56,3.78 g/kg),with 8 mice in each group.Upon the completion of the 14 days treatment,the rats had their TCM Syndrome scores assessed;their fecal water content,initial black stool excretion time,and small intestine propulsion rate measured;their colon tissue morphology observed by HE staining;their serum levels of IL-6,TNF-α,and IL-1β detected by ELISA;their expressions of occludin and zonula occludens-1(ZO-1)in colon tissues detected by immunohistochemistry;their mRNA expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by RT-qPCR;and their protein expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by Western blot.RESULTS Compared to the blank group,the model group had higher TCM Syndrome scores(P＜0.01);lower fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);longer initial black stool excretion time(P＜0.01);more mucosal edema in colon tissue,obvious inflammatory infiltration,and glandular disorder;increased serum levels of IL-6,TNF-α and IL-1 β(P＜0.05);decreased colon expressions of ZO-1 and occludin(P＜0.01);and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.01).Compared to the model group,both the medium-dose Yunpi Tongchang Formula group and the mosapride citrate tablet group demonstrated effectively reduced TCM syndrome scores(P＜0.01);increased fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);and shorter initial black stool excretion time(P＜0.01);improved colon mucosal edema and inflammatory infiltration;decreased serum levels of IL-6,TNF-α and IL-1β(P＜0.01);upregulated protein expressions of ZO-1 and occludin(P＜0.01);and downregulated mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.05,P＜0.01).CONCLUSION Yunpi Tongchang Formula significantly ameliorates constipation symptoms in OIC rat models of Spleen-Kidney Yang Deficiency Syndrome because of its efficacy in attenuating intestinal inflammation and preserving the integrity of intestinal epithelial barrier structure,with its mechanistic action in downregulating TLR4/MyD88/NF-κB signaling pathway activation.

Objective:To observe the changes of growth parameters and glucose and lipid metabolism indexes in GHD children treated with rhGH for 2 years, and analyze the influence of sex and age on these indexes.Methods:Clinical data of children with 80 cases GHD admitted to the Endocrine and Nutrition Clinic of the Beijing Children's Hospital affiliated to the Capital Medical University from July 2016 to December 2022 were analyzed retrospectively. All patients were treated with rhGH. The growth parameters, growth factors, glucose metabolism and lipid metabolism indexes were collected and calculated before treatment and at 3, 6, 12, 18 and 24 months after treatment, the influence of sex and age on these indexes and the correlations between these indicators and height growth rate were analyzed. Independent-sample t-test was used to compare two groups with normal distribution, one-way ANOVA was used to compare multiple groups, and repeated measures ANOVA was used to compare the mean of each time point within groups. The nonparametric rank sum test was used for the comparison of non-normal distribution measurement data. Pearson correlation analysis was used to analyze the correlation between HGV and each index.Results:A total of 80 children were enrolled, 39 boys and 41 girls. Grouped by age, there were 20 in the 3.00-5.99 age group, 41 in the 6.00-9.99 age group, and 19 in the ≥10.00 age group. All patients after 24 months of treatment had a higher height ((135.13±13.17) cm), HtSDS (-0.73 (-1.04, -0.41)), body weight (29.25 (23.13, 35.00) kg), weight standard deviation score (WtSDS) (-0.44 (-1.03, 0.03)), and body mass index (BMI) (15.99 (14.90,16.92) kg/m 2) compared to before treatment ((115.44±12.87) cm, -2.11 (-2.57, -2.03), 20.00 (16.00,25.00) kg, -1.48 (-2.12, -0.89) and 15.30 (14.45, 16.21) kg/m 2) all increased, and the differences were statistically significant (all P<0.05). The increase in HtSDS in the group aged 3.00-5.99 (1.74±0.29) was higher than that in the group aged 6.00-9.99 (1.57±0.33) and ≥10.00 (1.39±0.45), and the difference was statistically significant ( F=4.84, P=0.010). All patients showed an increase in insulin-like growth factor 1 (IGF-1) (329.50 (268.00, 417.25) μg/L) and insulin-like growth factor binding globulin 3 (IGFBP-3) (6.27 (5.50,6.95) mg/L) after 24 months of treatment compared to before treatment (131.50 (96.48,177.25) μg/L, 4.07 (3.60,4.88) mg/L), with statistical significance (all P<0.05). After treatment for 3 months, 6 months, 12 months, 18 months, and 24 months, children aged ≥ 10.00 years old with IGF-1 (353.00 (221.00, 493.00), (414.84±147.91), 441.00 (287.00, 578.00), (421.68±138.30), 376.00 (290.00, 581.00) μg/L) were higher than these in 3.00-5.99 years old group (181.00 (151.25, 237.75), (216.30±68.48), 239.50 (216.75, 325.00), (284.30±89.12), 293.00 (245.25, 343.75)) μg/L and 6.00-9.99 age group (253.00 (193.50, 345.50), (294.59±90.37), 284.00 (217.50, 377.50), (325.76±90.04), 345.00 (265.00, 431.00) μg/L, the difference was statistically significant (all P<0.05). At 3 months, 6 months, 12 months, and 18 months of treatment, IGFBP-3 levels were observed in children aged ≥ 10.00 years old (6.15 (5.52, 6.46), (6.56±1.26), (6.78±1.33), (6.78±1.38) mg/L) higher than 3.00-5.99 years old group (4.69 (4.43,5.11), (5.18±0.63), (5.61±0.84), (6.08±1.00) mg/L) and 6.00-9.99 age group (5.51 (4.76, 6.35), (5.61±0.81), (5.72±0.78), (6.03±0.80) mg/L, the difference was statistically significant (all P<0.05). All children with HbA1C (5.40 (5.20, 5.58)%), fasting blood glucose (5.06 (4.76, 5.24) mmol/L), triglycerides (0.67 (0.53, 1.02) mmol/L), TyG index (2.24±0.48), and triglyceride/HDL-C ratio (1.05 (0.73, 1.50)) after 24 months of treatment compared to before treatment (5.10 (5.00, 5.28)%, 4.78 (4.51, 5.09) mmol/L, 0.57 (0.47, 0.72) mmol/L, (1.92±0.36), 0.86 (0.65, 1.08). The level of cholesterol increased, and the total cholesterol (3.74 (3.39, 4.31) mmol/L) decreased compared to before treatment (3.95(3.64, 4.54) mmol/L), with statistical significance (all P<0.05). Female patients had higher levels of triglycerides (0.79 (0.59, 1.09) mmol/L) and TyG index (2.31±0.49) than male patients (0.66 (0.53,0.89) mmol/L, (2.16±0.46)) after 18 months of treatment. The triglyceride/HDL-C at 12 months (1.10(0.67, 1.93)), 18 months (1.16(0.83, 1.68)), and 24 months (1.26 (0.79, 1.81)) of treatment ratio was also higher than male patients (0.76 (0.61, 1.09), 0.90 (0.72, 1.08), 0.98 (0.66, 1.30)). Female HDL-C levels at 18 months (1.52 (1.29,1.75) mmol/L) and 24 months (1.45(1.29,1.76) mmol/L) of treatment were significantly lower in males (1.72 (1.45, 1.84), 1.59 (1.43, 1.92) mmol/L) with statistical significance (all P<0.05). HGV was positively correlated with IGF-1 at 12 months ( r=0.243, P=0.030) , 18 months ( r=0.277, P=0.013) and 24 months ( r=0.289, P=0.009), and it was positively correlated with IGFBP-3 at 18 months ( r=0.242, P=0.030) and 24 months ( r=0.236, P=0.035), but it was negatively correlated with HDL-C at 18 months ( r=-0.331, P=0.003) and 24 months ( r=-0.281, P=0.012). Conclusions:RhGH can obviously improve HtSDS and WtSDS in GHD children. Growth factors, glucose metabolism and lipid metabolism should be monitored during the treatment. Especially for female patients (≥10.00 years old), we should closely monitor the indexes of glucose and lipid metabolism in order to avoid metabolic diseases.

Objective:To investigate the epidemiological characteristics and trends of birth defects related to assisted reproductive technology (ART) in Jiangxi Province from 2014 to 2023, and to explore the correlation factors of birth defect occurrence.Methods:A retrospective collection of ART treatment data and follow-up results from January 2014 to December 2023 across 18 reproductive centers in Jiangxi Province was conducted. The trend of birth defects and the rank order of defect types were analyzed. Exact probability methods were used to estimate the 95% confidence intervals ( CI) of the incidence rates, and Poisson regression was applied to identify independent correlation factors. Results:A total of 65 003 ART offspring were included in this study, comprising 2 025 offspring from intrauterine insemination (IUI) and 62 978 from in vitro fertilization and embryo transfer (IVF-ET). The overall incidence of birth defects was 13.46‰ (95% CI: 12.59‰-14.38‰), with 9.38‰ (95% CI: 5.66‰-14.61‰) for IUI and 13.59‰ (95% CI:12.70‰-14.53‰) for IVF-ET. The incidence of birth defects showed a decreasing trend from 2014 to 2023 (17.11‰ to 11.47‰, Ptrend=0.003). The top three birth defect types were circulatory system defects (3.71‰, 95% CI: 3.25‰-4.21‰), musculoskeletal system defects (2.37‰, 95% CI: 2.01‰-2.77‰), and congenital malformations of the face, ears, eyes, and neck (1.23‰, 95% CI: 0.98‰-1.53‰). Univariate analysis indicated that male offspring from IVF-ET had a higher incidence of birth defects than that in female offspring (14.72‰ vs. 12.31‰, P=0.009). Additionally, gestational age, birth weight, fetal number, cause of infertility, and year of delivery were significantly associated with birth defect incidence in IVF-ET offspring ( P<0.001, P<0.001, P<0.001, P=0.025, P=0.037). Multivariate analysis showed that in singleton pregnancies, male offspring, gestational age 32-36 weeks birth weight <1 500 g, and infertility with bilateral factors were independent risk factors for birth defects ( OR=1.21, 95% CI: 1.00-1.47, P=0.046; OR=1.90,95% CI: 1.41-2.56, P<0.001; OR=3.37, 95% CI: 1.33-8.51, P=0.010; OR=1.38, 95% CI: 1.12-1.69, P=0.003), while in multiple pregnancies, male offspring, gestational age <32 weeks, gestational age 32-36 weeks, birth weight <1 500 g, birth weight 1 500-2 499 g, maternal age 25-29 years and maternal age 30-34 years were independent risk factors ( OR=1.25, 95% CI: 1.03-1.52, P=0.023; OR=2.06, 95% CI: 1.35-3.15, P=0.001; OR=1.32,95% CI: 1.05-1.66, P=0.016; OR=1.98,95% CI: 1.19-3.28, P=0.009; OR=2.06,95% CI: 1.64-2.60, P<0.001; OR=2.00, 95% CI: 1.31-3.06, P=0.001; OR=1.90,95% CI: 1.24-2.92, P=0.003). Conclusion:Over the past 10 years, the incidence of birth defects in ART offspring in Jiangxi Province has shown a decreasing trend annually, with circulatory system malformations being the most common. The occurrence of birth defects in IVF offspring is primarily associated with maternal and infant characteristics, such as gender, gestational age, birth weight, number of fetuses, and cause of infertility, independent of ART treatment factors.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.