Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

ObjectiveTo investigate the current awareness and optimization recommendations on pneumonia with unknown etiology (PUE) surveillance among Shanghai healthcare professionals, and to provide evidence for the improvement of the surveillance system. MethodsIn December 2024, healthcare professional participants from diverse medical and health institutions were randomly selected within each stratum using a stratified cluster sampling method in all 16 districts of Shanghai for questionnaire surveys on their knowledge and suggestions for optimization of the PUE surveillance system. Descriptive statistics analyses, multivariate logistic regressions, and content analyses were used for data analyses. ResultsA total of 385 survey subjects were involved in the study, including 119 professional staffs from disease prevention and control centers and 266 from medical institutions. Those who understood the case definition for PUE correctly accounted for 67.01% (258/385). Multivariate regression model analyses showed that female gender (aOR=2.22, 95%CI: 1.36‒3.66), professionals from disease control institutions (aOR=2.02, 95%CI: 1.12‒3.72), and those who self-assessed as being familiar with the monitoring system (aOR=2.18, 95%CI:1.23‒3.89) had better understanding of the definition. Overall, 89.61% (345/385) of the survey subjects acknowledged the necessity of the surveillance system. Small number of cases meeting the case definition (54.46%, 214/379), insufficient diagnostic awareness (39.84%, 151/379), and lack of incentives for case reporting (29.29%, 111/379) were major problems for the current surveillance system, with variations observed across different types of institutions. Suggested segments for optimizing the surveillance system included monitoring purpose, case definition, form of monitoring and reporting procedure, organization mechanism, and epidemiological investigation and response. ConclusionThe necessity of PUE surveillance is commonly recognized among healthcare workers. However, the existing system falls short in terms of mastery of case definition and overall surveillance adaptability. There is an urgent need for optimization and improvement to enhance the capacity for preventing and controlling emerging and sudden respiratory infectious diseases.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To evaluate the role of splenic sympathetic nerve-regulated infiltration and polarization of dorsal root ganglion (DRG) macrophages in diabetic neuropathic pain (DNP) in mice.Methods:Forty-eight specific pathogen-free male C57BL/6 mice, aged 6 weeks, weighing 20-22 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (Con group), DNP group, DNP plus sham operation group (DNP+ Sham group), and diabetes mellitus induced by DNP plus splenic sympathetic denervation group (DNP+ SS group). In DNP+ SS group, the splenic sympathetic denervation procedures were performed using 6-hydroxydopamine solution, while a solvent of 0.2% ascorbic acid saline solution was used as a substitute for 6-hydroxydopamine solution in DNP+ Sham group. After a two-week recovery, the diabetes mellitus was induced by intraperitoneal injection of streptozotocin 120 mg/kg in mice at 8 weeks of age. The mechanical paw withdrawal threshold (MWT) were measured on day 1 before developing the model and on days 7, 14, 21 and 28 after developing the model. After the last behavioral testing, the DRG was taken after anesthesia for determination of the expression of the macrophage marker ionized calcium-binding adaptor molecule 1(Iba1), calcitonin gene-related peptide (CGRP), and tumor necrosis factor-α (TNF-α) (by immunofluorescence) and expression of M1 phenotype markers (CD16, TNF-α, inducible nitric oxide synthase [iNOS]) and M2 phenotype markers (interleukin-10 [IL-10], transforming growth factor-β1 [TGF-β1], and CD206) mRNA (using quantitative real-time polymerase chain reaction). Results:Compared with Con group, the MWT was significantly decreased on days 14, 21 and 28 after developing the model, the expression of CGRP and TNF-α in the DRG was up-regulated, the count of Iba1-positive cells was increased, the expression of CD16, TNF-α and iNOS mRNA was up-regulated ( P<0.05), and no significant change was found in the expression of IL-10, TGF-β1 and CD206 in DNP group ( P>0.05). Compared with DNP group and DNP+ Sham group, the MWT was significantly increased on days 14, 21 and 28 after developing the model, the expression of CGRP and TNF-α in the DRG was down-regulated, the count of Iba1-positive cells was decreased, the expression of CD16, TNF-α and iNOS mRNA was down-regulated, and the expression of IL-10, TGF-β1 and CD206 mRNA was up-regulated in DNP+ SS group ( P<0.05), and no significant change was found in the aforementioned parameters at each time point in DNP and DNP+ Sham groups ( P>0.05). Conclusions:Activation of splenic sympathetic nerve can promote the infiltration and polarization of DRG macrophages, thus participating in the process of diabetic neuropathic pain in mice.

Objective:Empirically analyzing the improvement path of the municipal government's public health governance performance in Guizhou province,to providing an effective reference for the in-depth implementation of the Healthy China strategy.Methods:Based on the TOE framework,9 city(prefecture)governments in Guizhou province are selected as research cases,the fuzzy set qualitative comparative analysis method and the necessary condition analysis method are jointly applied to explore the bottleneck effect,linkage effect,and path selection of big data technology,technological infrastructure,attention intensity and other conditional factors on the Guizhou provincial government's improvement of public health governance performance from the three dimensions of"technology-organization-environment".Results:(1)A single condition does not constitute a necessary condition for high public health governance performance;(2)Big data technology plays a universal role in generating high public health governance performance for governments and is a key technological engine for governance;(3)There are two main driving models for improving the performance of public health governance by the Guizhou provincial Government,namely the"technology led+environment assisted"model and the"technology led+organization and environment assisted"model.Conclusions:The effective combination of technology,organization,and environmental elements within each mode can enhance the performance of government public health governance in a"different paths leading to the same goal"manner.

Premature ovarian insufficiency(POI)is a disease that seriously affects the health and life of women,which is also one of the main causes of female infertility.The incidence of POI is increasing in recent years.The diagnostic criteria of POI are not uniform,and different diagnostic criteria have inconsistent thresholds for various indicators.Strict diagnostic criteria are more conducive to early detection and treatment of POI.At present,complementary and alternative therapies such as traditional Chinese medicine,acupuncture and moxibustion are widely used in the treatment of POI.This article reviewed the recent studies on the complementary and alternative therapy of traditional Chinese medicine in the treatment of POI,and finds that the dialectical treatment of traditional Chinese medicine is based on the perspective of traditional Chinese medicine theory and puts forward corresponding treatment plans for different dialectical types.For example,treatment from the kidney,tonifying kidney filling essence,regulating chongren;Treatment from the liver,soothing the liver,regulating qi,nourishing blood and softening the liver;Treatment from the heart and spleen,nourishing Yangming,tonifying the spleen and nourishing the heart.In terms of acupuncture treatment,regulating menstruation and promoting pregnancy and regulating the conception vessel and toning the governor vessel and toning the kidney are often used to treat POI.In addition,moxibustion regulates body function by stimulating the bladder meridian and conception vessel and governor vessel acupoints.Other methods,such as ear acupoint bean-pressing,acupoint thread-embedding and acupoint injection,have also shown potential in the treatment of POI.This article summarizes the role and characteristics of traditional Chinese medicine in the treatment of POI,in order to provide ideas and basis for clinical treatment of POI.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To evaluate the role of splenic sympathetic nerve-regulated infiltration and polarization of dorsal root ganglion (DRG) macrophages in diabetic neuropathic pain (DNP) in mice.Methods:Forty-eight specific pathogen-free male C57BL/6 mice, aged 6 weeks, weighing 20-22 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (Con group), DNP group, DNP plus sham operation group (DNP+ Sham group), and diabetes mellitus induced by DNP plus splenic sympathetic denervation group (DNP+ SS group). In DNP+ SS group, the splenic sympathetic denervation procedures were performed using 6-hydroxydopamine solution, while a solvent of 0.2% ascorbic acid saline solution was used as a substitute for 6-hydroxydopamine solution in DNP+ Sham group. After a two-week recovery, the diabetes mellitus was induced by intraperitoneal injection of streptozotocin 120 mg/kg in mice at 8 weeks of age. The mechanical paw withdrawal threshold (MWT) were measured on day 1 before developing the model and on days 7, 14, 21 and 28 after developing the model. After the last behavioral testing, the DRG was taken after anesthesia for determination of the expression of the macrophage marker ionized calcium-binding adaptor molecule 1(Iba1), calcitonin gene-related peptide (CGRP), and tumor necrosis factor-α (TNF-α) (by immunofluorescence) and expression of M1 phenotype markers (CD16, TNF-α, inducible nitric oxide synthase [iNOS]) and M2 phenotype markers (interleukin-10 [IL-10], transforming growth factor-β1 [TGF-β1], and CD206) mRNA (using quantitative real-time polymerase chain reaction). Results:Compared with Con group, the MWT was significantly decreased on days 14, 21 and 28 after developing the model, the expression of CGRP and TNF-α in the DRG was up-regulated, the count of Iba1-positive cells was increased, the expression of CD16, TNF-α and iNOS mRNA was up-regulated ( P<0.05), and no significant change was found in the expression of IL-10, TGF-β1 and CD206 in DNP group ( P>0.05). Compared with DNP group and DNP+ Sham group, the MWT was significantly increased on days 14, 21 and 28 after developing the model, the expression of CGRP and TNF-α in the DRG was down-regulated, the count of Iba1-positive cells was decreased, the expression of CD16, TNF-α and iNOS mRNA was down-regulated, and the expression of IL-10, TGF-β1 and CD206 mRNA was up-regulated in DNP+ SS group ( P<0.05), and no significant change was found in the aforementioned parameters at each time point in DNP and DNP+ Sham groups ( P>0.05). Conclusions:Activation of splenic sympathetic nerve can promote the infiltration and polarization of DRG macrophages, thus participating in the process of diabetic neuropathic pain in mice.

Objective:Empirically analyzing the improvement path of the municipal government's public health governance performance in Guizhou province,to providing an effective reference for the in-depth implementation of the Healthy China strategy.Methods:Based on the TOE framework,9 city(prefecture)governments in Guizhou province are selected as research cases,the fuzzy set qualitative comparative analysis method and the necessary condition analysis method are jointly applied to explore the bottleneck effect,linkage effect,and path selection of big data technology,technological infrastructure,attention intensity and other conditional factors on the Guizhou provincial government's improvement of public health governance performance from the three dimensions of"technology-organization-environment".Results:(1)A single condition does not constitute a necessary condition for high public health governance performance;(2)Big data technology plays a universal role in generating high public health governance performance for governments and is a key technological engine for governance;(3)There are two main driving models for improving the performance of public health governance by the Guizhou provincial Government,namely the"technology led+environment assisted"model and the"technology led+organization and environment assisted"model.Conclusions:The effective combination of technology,organization,and environmental elements within each mode can enhance the performance of government public health governance in a"different paths leading to the same goal"manner.