ObjectiveTo investigate the disruptive effects of perinatal exposure to the environmental endocrine disruptor bisphenol AF (BPAF) on hepatic lipid metabolism in prepubertal (postnatal day 21, PND21) male offspring rats, and to provide scientific evidence for assessing the obesogenic effect of BPAF. MethodsSprague-Dawley (SD) rats aged 8 weeks were used in this study. Pregnant rats were divided into BPAF dose groups (2, 10, 50 mg·kg⁻¹) and a vehicle control group (corn oil), with 6 confirmed pregnant females per group. Gavage administration started from gestational day 0 and continued until the end of lactation. At PND21, one male offspring per litter was randomly selected. Serum concentrations of glucose (GLU), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), leptin (LEP), free fatty acid (FFA), as well as oxidative stress markers superoxide dismutase (SOD) and malondialdehyde (MDA), were measured. Pathological changes in liver and adipose tissues were evaluated, and the expression levels of genes related to hepatic lipid metabolism were measured. ResultsCompared to the vehicle control group, the 50 mg·kg⁻¹ group showed significantly increased serum LEP and MDA levels in male offspring (P<0.05), and significant upregulation of hepatic lipoprotein lipase (Lpl), fatty acid synthetase (Fas), and peroxisome proliferator-activated receptor γ (Pparg) gene expression (P<0.05). The 2 mg·kg⁻¹ group exhibited a significant increase in adipocyte length (P<0.05), while the 50 mg·kg⁻¹ group showed significant increases in both adipocyte area and length (P<0.05). No significant abnormalities were observed in liver histopathological examination. ConclusionPerinatal exposure to 50 mg·kg⁻¹ BPAF induced adipocyte hypertrophy, elevated leptin levels, upregulation of lipid synthesis gene expression, and enhanced oxidative stress in prepubertal male offspring, suggesting that BPAF may exert environmental obesogenic effects by disrupting lipid metabolism pathways.

ObjectiveTo analyze the epidemiological characteristics and trends of varicella in Taizhou, Zhejiang Province from 2014 to 2023, and to provide evidence for surveillance, prevention, and control of varicella in Taizhou. MethodIndividual case data of varicella reported in Taizhou from 2014 to 2023 were collected and analyzed. Descriptive epidemiological methods were used to analyze the distribution characteristics of varicella, and Joinpoint regression models were applied to assess trends in incidence rates. ResultsA total of 29 845 cases of varicella were reported in Taizhou from 2014 to 2023, with an annual incidence rate of 47.65/100 000. A total of 22 varicella-related public health events were recorded, accounting for 13.25% of all reported outbreaks during the same period. The annual reported incidence rates for males and females were 51.49/100 000 and 43.56/100 000, respectively. The average annual incidence rate was significantly higher in males than that in females. The age of onset was mainly from 5 to 20 years old, with a total of 20 382 cases reported, accounting for 68.29% of the total cases. Students constituted the majority of cases (62.15%). A distinct seasonal pattern was observed, with a major incidence peak from November to January of the next year and a secondary peak period from May to June. Varicella cases were reported in all counties and districts. The average annual incidence rates in urban districts, mountainous counties and coastal cities were 53.28/100 000, 50.24/100 000 and 41.46/100 000, respectively. Joinpoint regression identified 2019 as a turning point in the overall incidence trend, dividing the period into two phases, but the changes in trend of the two phases were not statistically different (P>0.05). Age-specific analyses revealed divergent trends: incidence rates among the 1‒ and 5‒year-old groups showed steady declines over the 10-year period (APC=-8.481%, P=0.006; APC=-11.690%, P=0.006). The incidence rate of 10‒year-old group showed a rapid decreasing trend from 2019 to 2023 (APC=-21.670%, P=0.026). In contrast, the 15‒ and 20‒year-old groups showed significant increases during the first phase (APC=20.531%, P=0.001; APC=10.778%, P=0.038). ConclusionFrom 2014 to 2023, the reported incidence rate of varicella was higher in males than that in females. The highest average annual incidence rate occurred in the 10‒19-year-old age group, with regional variations observed across different areas. The peak incidence period was from November to January of the following year. The overall incidence of varicella in Taizhou was slightly lower than that of the national average level. However, the number of varicella-related outbreaks reported during the same period remained relatively high, underscoring the need for continued and comprehensive prevention and control measures.

Background Other infectious diarrhea (OID) refers to infectious diarrhea other than cholera, dysentery, and typhoid/paratyphoid fever. In the global climate change context, frequent extreme temperature events pose a significant threat to population health, yet the association between extreme temperatures and OID remains unclear. Objective To understand the impact of extreme temperature events on the incidence of OID in Taizhou region, and provide a scientific basis for formulating targeted public health intervention strategies. Methods Case data of OID from 2016 to 2024 and meteorological and pollutant data of Taizhou, Zhejiang during the same period were collected. The case data were derived from National Notifiable Infectious Diseases Reporting System, while the meteorological data and pollutant data were obtained from National Meteorological Science Data Center and Taizhou Ecology and Environment Bureau, respectively. An extreme heat event is defined as a period of two or more consecutive days in the warm season during which the daily mean temperature exceeds the 90th percentile value for that season. Similarly, an extreme cold event is defined as a period of two or more consecutive days in the cold season during which the daily mean temperature falls below the 10th percentile value. A distributed lag nonlinear model based on Poisson regression was used to assess the impact of extreme temperatures on OID incidence. Furthermore, subgroup analyses were conducted by gender and age. Results From 2016 to 2024, a total of 108 670 OID cases were reported in Taizhou, with higher incidence in males (61 253 cases) than females (47 417 cases). In terms of single-day lag effect, exposure to extreme cold presented an inverted U-shaped risk pattern: a significant risk effect began to emerge on the 4th day after exposure, continued to rise, and reached a peak on the 7th day (RR=1.044, 95%CI: 1.029, 1.058), whereas extreme heat had no significant impact. In terms of cumulative lag effect, exposure to extreme cold presented a J-shaped cumulative effect curve: short-term exposure (0-2 days) showed no risk effect, but as time extended (0-9 days), a risk effect emerged and reached the maximum risk value during the 0-12 d cumulative period (RR=1.243, 95%CI: 1.057, 1.461). In contrast, extreme heat had no cumulative lag effect. The subgroup analysis revealed that under extreme cold exposure, the single-day lag effects for both males and females exhibited an inverted U-shaped curve, with the risk peaking on day 7 for males (RR=1.045, 95%CI: 1.026, 1.065) and day 8 for females (RR=1.041, 95%CI: 1.019, 1.064). The risk pattern in the 1-5 years age group was similar to that of the overall population but with a higher effect size (RR=1.063, 95%CI: 1.041, 1.085). In terms of the cumulative lag effects, the cumulative risk curves for both males and females under extreme cold exposure showed a J-shaped pattern with varied risk profiles. Significant variations in risk patterns were observed across different age groups. No significant cumulative lag effects were observed for extreme heat exposure in any subgroup. Conclusion Extreme cold can increase the incidence of OID in Taizhou, and the risk effects are heterogeneous among different groups. No risk effect is observed for extreme heat.

Objective:To establish a gas chromatography-mass spectrometry method(GC-MS-MS)for determining the content of methyl p-toluenesulfonate(MTS),ethyl p-toluenesulfonate(ETS),and isopropyl p-toluenesulfonate(IPTS)in tosufloxacin tosylate hydrate.Methods:The HP-1MS(0.250 mm ×30 m,0.50 μm)column was used at progamming temperature,the injection temperature was 250 ℃.The MS conditions were as follow:the ionization mode was EI,the electron voltage was 70 V,the ion source temperature was 250 ℃,the scanning method was MRM,the quantitative ion pairs for MTS,ETS and IPTS were m/z 91 →65,m/z 155→91 and m/z 91→65.Results:The linearity ranges of MTS,ETS and IPTS were 48.779-975.59 ng·mL-1(r=0.998 5),54.586-1 091.7 ng·mL-1(r=0.998 4)and 46.241-924.82 ng·mL-1(r=0.999 8).The average recoveries were 99.47％,99.15％,98.83％(n=9).The MTS,ETS and IPTS were not detected in the 7 batches of tosufloxacin tosylate hydrate.Conclusion:The established method can be used for the determination of MTS,ETS,and IPTS content in tosufloxacin tosylate hydrate.

AIM:To investigate the antiviral effica-cy and mechanism of Qingre Xiaoyanning(QRXYN)in vivo,and provide experimental basis for their prevention and treatment of influenza A virus.METHODS:We constructed a mouse model infect-ed with influenza A H3N2 virus.To evaluate the therapeutic effect of QRXYN on influenza A virus,we measured the body weight changes,pathologi-cal changes in lung tissue,hemagglutination titer,and viral load in mouse.To evaluate the possible mechanism of QRXYN's anti influenza A virus infec-tion,we used the ELISA to measure the levels of TNF-α,IL-1β,IL-4,IFN-γ,and vascular cell adhesion molecule-1(VCAM-1)in mouse bronchoalveolar Ia-vage fluid;used flow cytometry to assess the pro-portions of macrophages(F4/80),helper T lympho-cytes(CD4+T lymphocytes),and natural killer(NK)cells in lung tissue;and used Western blotting to detect the expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MYD88),inhibitor of kappa B kinase-β(IKK-β),NF-kappa-B inhibitor al-pha(IκBα),and phospho-IKB alpha(p-IκBα)in lung tissue.RESULTS:Compared to the model group,both Oseltamivir and QRXYN can alleviate the se-verity of lung tissue lesions in mice,decrease the blood coagulation titer and viral load of mouse lung tissue(P＜0.01),lower the levels of TNF-α,IL-4,and VCAM-1 in bronchoalveolar lavage fluid(P＜0.05,P＜0.01),reduce the proportion of macro-phages(P＜0.05,P＜0.01),and increase the propor-tion of CD4+T lymphocytes and NK cells(P＜0.05,P＜0.01).Additionally,oseltamivir can reduce the ex-pression of MYD88 protein in mouse lungs(P＜0.05),while QRXYN can decrease the expression of IKK-β and P-IκBα proteins in mouse lungs(P＜0.05).CONCLUSION:QRXYN have good in vivo antiviral ef-fects against the influenza A virus,and their mecha-nism may be related to the regulation of the immu-nologic function and NF-κB signal pathway.

Objective:To investigate the association between serum IgG concentration and renal prognosis in patients with IgA nephropathy (IgAN).Methods:It was a multi-center retrospective cohort study, patients with biopsy proven primary IgAN who were recorded in the Chinese IgA Nephropathy Information Registration System between April 1996 and September 2018 were included. Exclusion criteria were: (1) age <18 years; (2) <8 glomeruli in biopsy specimens; (3) estimated glomerular filtration rate (eGFR) <15 ml·min -1·(1.73 m 2) -1 at biopsy; (4) missing baseline serum IgG values; (5) incomplete follow-up data; (6) follow-up duration <12 months. Enrolled patients were divided into 3 groups according to the baseline tertiles of serum IgG: ≤9.50 g/L (G1 group), 9.51-11.99 g/L (G2 group), and ≥12.00 g/L (G3 group). Clinical, and pathological parameters were compared across groups. The endpoint events were defined as doubled serum creatinine level from baseline, or end-stage renal disease (ESRD). Results:A total of 1 976 IgAN patients were included in this study, 631 were in G1 group, 664 in G2 group, and 681 in G3 group. The comparison of baseline clinical data showed that there were statistically significant differences among the three groups in terms of gender, age, microscopic hematuria, edema, body mass index, systolic blood pressure, diastolic blood pressure, hemoglobin, serum creatinine, eGFR, 24-hour urine protein quantity, blood uric acid, blood albumin, serum IgA, serum IgM, the proportion of using immunosuppressants, and the proportion of using glucocorticoids (all P<0.05). In terms of pathology, the higher the serum IgG concentration, the relatively less severe the overall renal pathological damage. The results of univariate Cox regression analysis showed that gender, systolic blood pressure, diastolic blood pressure, hemoglobin, serum creatinine, eGFR, 24-hour urine protein quantity, total protein, serum albumin, globulin, serum IgG, Oxford renal pathological classification, glomerular sclerosis ratio, and glomerular IgM deposition were all associated with the occurrence of renal endpoint events (all P<0.05). Based on clinical practice and previous studies, after adjusting for gender, age, systolic blood pressure, diastolic blood pressure, eGFR, 24-hour urine protein quantity, body mass index, Oxford renal pathological classification, glomerular sclerosis ratio, and the use of renin-angiotensin-aldosterone system inhibitors, glucocorticoids, and immunosuppressants, multivariate Cox regression analysis showed that as a continuous variable, the baseline serum IgG level ( HR=0.91, 95% CI 0.87-0.96) was independently associated with the risk of renal endpoint events in IgAN patients; as a categorical variable, with serum IgG ≤ 9.50 g/L as the reference, serum IgG 9.51-11.99 g/L and serum IgG ≥ 12.00 g/L were independent factors for the occurrence of renal endpoint events in IgAN patients ( HR=0.69, 95% CI 0.49-0.96, P=0.027; HR=0.50, 95% CI 0.34-0.74, P<0.001). During a median follow-up of 33(21, 53) months started from the date of renal biopsy and continued until December 31, 2019, the median follow-up duration was 33 (21, 53) months, and a total of 232 patients (11.74%) reached the composite endpoint. Kaplan-Meier survival analysis showed that the higher the serum IgG concentration in patients with IgAN, the higher their cumulative renal survival rate (Log-rank test, χ2=47.176, P<0.001). Conclusion:The higher level of serum IgG at diagnosis is associated with better clinicopathologic features and renal outcomes, and may portend better renal survival in IgAN patients.

AIM:To investigate the antiviral effica-cy and mechanism of Qingre Xiaoyanning(QRXYN)in vivo,and provide experimental basis for their prevention and treatment of influenza A virus.METHODS:We constructed a mouse model infect-ed with influenza A H3N2 virus.To evaluate the therapeutic effect of QRXYN on influenza A virus,we measured the body weight changes,pathologi-cal changes in lung tissue,hemagglutination titer,and viral load in mouse.To evaluate the possible mechanism of QRXYN's anti influenza A virus infec-tion,we used the ELISA to measure the levels of TNF-α,IL-1β,IL-4,IFN-γ,and vascular cell adhesion molecule-1(VCAM-1)in mouse bronchoalveolar Ia-vage fluid;used flow cytometry to assess the pro-portions of macrophages(F4/80),helper T lympho-cytes(CD4+T lymphocytes),and natural killer(NK)cells in lung tissue;and used Western blotting to detect the expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MYD88),inhibitor of kappa B kinase-β(IKK-β),NF-kappa-B inhibitor al-pha(IκBα),and phospho-IKB alpha(p-IκBα)in lung tissue.RESULTS:Compared to the model group,both Oseltamivir and QRXYN can alleviate the se-verity of lung tissue lesions in mice,decrease the blood coagulation titer and viral load of mouse lung tissue(P＜0.01),lower the levels of TNF-α,IL-4,and VCAM-1 in bronchoalveolar lavage fluid(P＜0.05,P＜0.01),reduce the proportion of macro-phages(P＜0.05,P＜0.01),and increase the propor-tion of CD4+T lymphocytes and NK cells(P＜0.05,P＜0.01).Additionally,oseltamivir can reduce the ex-pression of MYD88 protein in mouse lungs(P＜0.05),while QRXYN can decrease the expression of IKK-β and P-IκBα proteins in mouse lungs(P＜0.05).CONCLUSION:QRXYN have good in vivo antiviral ef-fects against the influenza A virus,and their mecha-nism may be related to the regulation of the immu-nologic function and NF-κB signal pathway.

Objective:To establish a gas chromatography-mass spectrometry method(GC-MS-MS)for determining the content of methyl p-toluenesulfonate(MTS),ethyl p-toluenesulfonate(ETS),and isopropyl p-toluenesulfonate(IPTS)in tosufloxacin tosylate hydrate.Methods:The HP-1MS(0.250 mm ×30 m,0.50 μm)column was used at progamming temperature,the injection temperature was 250 ℃.The MS conditions were as follow:the ionization mode was EI,the electron voltage was 70 V,the ion source temperature was 250 ℃,the scanning method was MRM,the quantitative ion pairs for MTS,ETS and IPTS were m/z 91 →65,m/z 155→91 and m/z 91→65.Results:The linearity ranges of MTS,ETS and IPTS were 48.779-975.59 ng·mL-1(r=0.998 5),54.586-1 091.7 ng·mL-1(r=0.998 4)and 46.241-924.82 ng·mL-1(r=0.999 8).The average recoveries were 99.47％,99.15％,98.83％(n=9).The MTS,ETS and IPTS were not detected in the 7 batches of tosufloxacin tosylate hydrate.Conclusion:The established method can be used for the determination of MTS,ETS,and IPTS content in tosufloxacin tosylate hydrate.

Objective:To investigate the association between serum IgG concentration and renal prognosis in patients with IgA nephropathy (IgAN).Methods:It was a multi-center retrospective cohort study, patients with biopsy proven primary IgAN who were recorded in the Chinese IgA Nephropathy Information Registration System between April 1996 and September 2018 were included. Exclusion criteria were: (1) age <18 years; (2) <8 glomeruli in biopsy specimens; (3) estimated glomerular filtration rate (eGFR) <15 ml·min -1·(1.73 m 2) -1 at biopsy; (4) missing baseline serum IgG values; (5) incomplete follow-up data; (6) follow-up duration <12 months. Enrolled patients were divided into 3 groups according to the baseline tertiles of serum IgG: ≤9.50 g/L (G1 group), 9.51-11.99 g/L (G2 group), and ≥12.00 g/L (G3 group). Clinical, and pathological parameters were compared across groups. The endpoint events were defined as doubled serum creatinine level from baseline, or end-stage renal disease (ESRD). Results:A total of 1 976 IgAN patients were included in this study, 631 were in G1 group, 664 in G2 group, and 681 in G3 group. The comparison of baseline clinical data showed that there were statistically significant differences among the three groups in terms of gender, age, microscopic hematuria, edema, body mass index, systolic blood pressure, diastolic blood pressure, hemoglobin, serum creatinine, eGFR, 24-hour urine protein quantity, blood uric acid, blood albumin, serum IgA, serum IgM, the proportion of using immunosuppressants, and the proportion of using glucocorticoids (all P<0.05). In terms of pathology, the higher the serum IgG concentration, the relatively less severe the overall renal pathological damage. The results of univariate Cox regression analysis showed that gender, systolic blood pressure, diastolic blood pressure, hemoglobin, serum creatinine, eGFR, 24-hour urine protein quantity, total protein, serum albumin, globulin, serum IgG, Oxford renal pathological classification, glomerular sclerosis ratio, and glomerular IgM deposition were all associated with the occurrence of renal endpoint events (all P<0.05). Based on clinical practice and previous studies, after adjusting for gender, age, systolic blood pressure, diastolic blood pressure, eGFR, 24-hour urine protein quantity, body mass index, Oxford renal pathological classification, glomerular sclerosis ratio, and the use of renin-angiotensin-aldosterone system inhibitors, glucocorticoids, and immunosuppressants, multivariate Cox regression analysis showed that as a continuous variable, the baseline serum IgG level ( HR=0.91, 95% CI 0.87-0.96) was independently associated with the risk of renal endpoint events in IgAN patients; as a categorical variable, with serum IgG ≤ 9.50 g/L as the reference, serum IgG 9.51-11.99 g/L and serum IgG ≥ 12.00 g/L were independent factors for the occurrence of renal endpoint events in IgAN patients ( HR=0.69, 95% CI 0.49-0.96, P=0.027; HR=0.50, 95% CI 0.34-0.74, P<0.001). During a median follow-up of 33(21, 53) months started from the date of renal biopsy and continued until December 31, 2019, the median follow-up duration was 33 (21, 53) months, and a total of 232 patients (11.74%) reached the composite endpoint. Kaplan-Meier survival analysis showed that the higher the serum IgG concentration in patients with IgAN, the higher their cumulative renal survival rate (Log-rank test, χ2=47.176, P<0.001). Conclusion:The higher level of serum IgG at diagnosis is associated with better clinicopathologic features and renal outcomes, and may portend better renal survival in IgAN patients.

Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.