Objective:To evaluate the immunogenicity and immune persistence of human rabies vaccine (Vero cell) in healthy people aged 10-17 years and compare it with a group of adults aged 18-60 years.Methods:This study was conducted between July 2021 and November 2022 with Shangyu district and Shengzhou city of Shaoxing city, Zhejiang Province selected as the research sites. Zagreb regimen (2-1-1 schedule) and Essen regimen (1-1-1-1-1 schedule) were used for rabies vaccine administration. Serum samples were collected at different time points before and after immunization to compare the differences in seropositivity rates and geometric mean concentrations (GMC) between the 10-17 age group and the 18-60 age group.Results:A total of 1 200 healthy participants aged 10-60 were included, with 157 individuals (13.1%) in the 10-17 age group and 1 043 individuals (86.9%) in the 18-60 age group. Both groups displayed a nearly 100% seropositivity rate at 3, 6 and 12 months, and the participants in the same age group had similar antibody levels. The GMC of antibodies gradually increased after vaccination and peaked on 14 d. The 10-17 age group showed higher GMC of antibodies than the 18-60 age group at 14 d after the first dose (Zagreb regimen: 81.85 IU/ml vs 63.15 IU/ml, t=2.411, P=0.018; Essen regimen: 86.61 IU/ml vs 69.24 IU/ml, t=3.906, P<0.001). Similar differences were observed in the GMC of antibodies at 14 d and 3 months after the full vaccination course, but these differences gradually decreased and disappeared at 6 and 12 months after vaccination. Conclusions:Human rabies vaccine (Vero cell) has lasting immune protection in all participants within one year after vaccination, with no significant differences between the two vaccination regimens. Participants aged 10-17 have higher antibody levels compared to adults aged 18-60, but there is no significant difference in immune persistence between the two age groups.

Against the backdrop of the global acceleration of cervical cancer elimination, China has been promoting pilot programs offering free or subsidized HPV vaccination for eligible girls. In 2022, Zhejiang Province initiated a free bivalent HPV vaccination program for eligible girls, expanding from pilot areas to the whole province. Through key measures such as effective multi-sectoral collaboration, full financial support, comprehensive health education and high-quality vaccination services, the program was successfully implemented. However, challenges were encountered during the implementation of the program, including difficulties in target population definition and HPV vaccine selection, as well as significant gap between vaccination intention and behavior. This article systematically analyzes the practices and challenges faced by Zhejiang Province, and proposes corresponding strategies and suggestions based on the best practices both domestically and internationally. It aims to provide references for the implementation of similar programs in other regions or even integrating HPV vaccine into the immunization program.

Since the introduction of human papillomavirus (HPV) vaccines, countries around the world have actively promoted large-scale vaccination with HPV vaccines to improve their coverage for target populations. This study conducts a multidimensional analysis to quantify the policies, implementation models and evaluation outcomes of the free HPV vaccination program across countries at high, upper-middle and lower-middle income levels. The results reveal distinct patterns in implementation and evaluation among these countries. The results also suggest that China can learn from successful international experiences to explore more effective vaccination strategies to increase coverage. In parallel, it is essential to develop a scientifically grounded evaluation framework and conduct systematic evaluations to effectively support the continuous implementation of the free HPV vaccination program for target populations in China. Furthermore, China may consider incorporating appropriate HPV vaccines into the National Immunization Program and dynamically adjusting vaccine types as needed to accelerate the elimination of cervical cancer.

Against the backdrop of the global acceleration of cervical cancer elimination, China has been promoting pilot programs offering free or subsidized HPV vaccination for eligible girls. In 2022, Zhejiang Province initiated a free bivalent HPV vaccination program for eligible girls, expanding from pilot areas to the whole province. Through key measures such as effective multi-sectoral collaboration, full financial support, comprehensive health education and high-quality vaccination services, the program was successfully implemented. However, challenges were encountered during the implementation of the program, including difficulties in target population definition and HPV vaccine selection, as well as significant gap between vaccination intention and behavior. This article systematically analyzes the practices and challenges faced by Zhejiang Province, and proposes corresponding strategies and suggestions based on the best practices both domestically and internationally. It aims to provide references for the implementation of similar programs in other regions or even integrating HPV vaccine into the immunization program.

Since the introduction of human papillomavirus (HPV) vaccines, countries around the world have actively promoted large-scale vaccination with HPV vaccines to improve their coverage for target populations. This study conducts a multidimensional analysis to quantify the policies, implementation models and evaluation outcomes of the free HPV vaccination program across countries at high, upper-middle and lower-middle income levels. The results reveal distinct patterns in implementation and evaluation among these countries. The results also suggest that China can learn from successful international experiences to explore more effective vaccination strategies to increase coverage. In parallel, it is essential to develop a scientifically grounded evaluation framework and conduct systematic evaluations to effectively support the continuous implementation of the free HPV vaccination program for target populations in China. Furthermore, China may consider incorporating appropriate HPV vaccines into the National Immunization Program and dynamically adjusting vaccine types as needed to accelerate the elimination of cervical cancer.

Objective:To evaluate the immunogenicity and immune persistence of human rabies vaccine (Vero cell) in healthy people aged 10-17 years and compare it with a group of adults aged 18-60 years.Methods:This study was conducted between July 2021 and November 2022 with Shangyu district and Shengzhou city of Shaoxing city, Zhejiang Province selected as the research sites. Zagreb regimen (2-1-1 schedule) and Essen regimen (1-1-1-1-1 schedule) were used for rabies vaccine administration. Serum samples were collected at different time points before and after immunization to compare the differences in seropositivity rates and geometric mean concentrations (GMC) between the 10-17 age group and the 18-60 age group.Results:A total of 1 200 healthy participants aged 10-60 were included, with 157 individuals (13.1%) in the 10-17 age group and 1 043 individuals (86.9%) in the 18-60 age group. Both groups displayed a nearly 100% seropositivity rate at 3, 6 and 12 months, and the participants in the same age group had similar antibody levels. The GMC of antibodies gradually increased after vaccination and peaked on 14 d. The 10-17 age group showed higher GMC of antibodies than the 18-60 age group at 14 d after the first dose (Zagreb regimen: 81.85 IU/ml vs 63.15 IU/ml, t=2.411, P=0.018; Essen regimen: 86.61 IU/ml vs 69.24 IU/ml, t=3.906, P<0.001). Similar differences were observed in the GMC of antibodies at 14 d and 3 months after the full vaccination course, but these differences gradually decreased and disappeared at 6 and 12 months after vaccination. Conclusions:Human rabies vaccine (Vero cell) has lasting immune protection in all participants within one year after vaccination, with no significant differences between the two vaccination regimens. Participants aged 10-17 have higher antibody levels compared to adults aged 18-60, but there is no significant difference in immune persistence between the two age groups.

Chlorfenapyr,an emerging synthetic pesticide,has been linked to a growing number of poisoning incidents,attributed to heightened human exposure as its application becomes more widespread.However,the toxicokinetics and toxicology of chlorfenapyr remain incompletely understood.Research since the 1990s,including animal experiments,has illuminated the absorption,distribution,excretion,and metabolism of chlorfenapyr.Toxicological investigations have revealed that the primary toxicity of chlorfenapyr is the uncoupling of oxidative phosphorylation.Chlorfenapyr exposure in humans and other animals can lead to various toxic effects,including neurotoxicity,cardiotoxicity,skeletal muscle toxicity,genotoxicity,reproductive and developmental toxicity,renal toxicity,splenic toxicity,and hematotoxicity.This article presents a comprehensive review of the toxicokinetics and toxicology of chlorfenapyr,integrating data from animal experiments,human cell line studies,clinical reports,and human autopsy.Its objective is to raise clinical awareness regarding chlorfenapyr poisoning and offer valuable references for its treatment and management.

Objective To evaluate the feasibility of emergency percutaneous coronary intervention(PCI)with extracorporeal membrane oxygenation(ECMO)support in critically ill patients with acute myocardial infarction(AMI)and cardiogenic shock(CS).Methods Retrospective analysis of clinical data of AMI combined with CS patients admitted to the department of emergency of the Second Hospital of Hebei Medical University from December 2018 to December 2021,including gender,age,body mass index(BMI),past history(smoking,coronary heart disease,arrhythmia,diabetes,hypertension,hyperlipidemia,cerebrovascular disease);acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score,highest vasoactive-inotropic score(VIS)within 24 hours of admission,the worst auxiliary examination values within 24 hours after admission:blood lactic acid(Lac),arterial partial pressure of oxygen(PaO2),cardiac troponin I(cTnI),alanine aminotransferase(ALT),total bilirubin(TBil),creatinine(Cr),serum potassium,left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF)],presence of malignant arrhythmia or cardiac arrest during emergency PCI,completion of PCI,and the 30-day prognosis,etc.Patients were divided into an ECMO group and a non-ECMO group based on whether ECMO was applied,to analyze differences in the above indicators between the two groups.Results There were no statistically significant differences between the ECMO group and the non-ECMO group in terms of gender,age,BMI,past history,APACHEⅡ,VIS and the worst auxiliary examination value within 24 hours after admission.The incidence of malignant arrhythmia or cardiac arrest events and 30-day mortality rate during emergency PCI in the ECMO group were significantly lower than those in the non-ECMO group[the incidence of malignant arrhythmia or cardiac arrest during emergency PCI was 17.9％(7/39)vs.45.0％(9/20),and the 30-day mortality was 46.2％(18/39)vs.75.0％(15/20),both P<0.05].The completion rate of PCI in the ECMO group was significantly higher than that in the non-ECMO group[100.0％(39/39)vs.80.0％(16/20),P<0.05].Conclusions For critically ill patients with AMI combined with CS,ECMO support can reduce the risk of malignant arrhythmia or cardiac arrest during emergency PCI,increase the completion rate of PCI,and reduce the 30-day mortality.With the support of the ECMO team,ECMO support emergency PCI is feasible.

Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Objective:To investigate the effects of diquat (DQ) on the expression of intestinal pyroptosis-related proteins and tight junction proteins in rats, and to analyze the role of pyroptosis in the intestinal injury of rats with acute DQ poisoning.Methods:A total of 36 Wistar male rats were randomly divided into control group, and 3 hours, 12 hours, 36 hours and 3 days exposure groups, with 6 rats in each group. Each exposure group was given 1/2 median lethal dose (LD50) of 115.5 mg/kg DQ by one-time gavage. The control group was given the same amount of normal saline by gavage. The control group was anesthetized at 3 hours after DQ gavage to take jejunal tissues; each exposure group was anesthetized at 3 hours, 12 hours, 36 hours, and 3 days after DQ gavage to take jejunal tissues, respectively. The general conditions of the rats were recorded. The pathological changes of jejunum tissue were observed by hematoxylin-eosin (HE) staining. The expression of intestinal pyroptosis-related proteins [NOD-like receptor protein 3 (NLRP3), cysteine aspartate-specific protease 1 (caspase-1), Gasdemin D (GSDMD)] in the intestinal tissues was observed by immunohistochemical staining. Western blotting was used to detect the expression of intestinal pyroptosis-related proteins and intestinal tight junction proteins (Occludin and Claudin-1).Results:Light microscopy showed that pathological changes occurred in jejunum tissue at the early stage of exposure (3 hours), and the injury was the most serious in the 12 hours exposure group, with a large number of inflammatory cells infiltrating in the tissue, and the damage was significantly reduced after 3 days exposure. Immunohistochemical results showed that NLRP3, caspase-1 and GSDMD were expressed in the jejunal mucosa of the control group and the exposure groups, and the positive cells in the control group were less expressed with light staining. The expression of the above proteins in the exposed group was increased significantly and the staining was deep. Western blotting results showed that compared with the control group, the expression of NLRP3 protein in jejunum tissues of all groups was increased, with the most significant increase in the 36 hours group (NLRP3/β-actin: 1.47±0.06 vs. 0.43±0.14, P < 0.01). Compared with the control group, the expression of GSDMD protein in the 3 hours, 12 hours and 36 hours exposure groups increased, and the expression of GSDMD protein in the 3 hours and 12 hours exposure groups increased significantly (GSDMD/β-actin: 1.04±0.40, 1.25±0.15 vs. 0.65±0.25, both P < 0.05). The expression of caspase-1 protein was increased in 36 hours exposure group compared with the control group (caspase-1/β-actin: 1.44±0.34 vs. 0.98±0.19, P > 0.05). Compared with the control group, the expression of Occludin and Claudin-1 proteins in each exposure group decreased, and the expression of Occludin proteins was significantly decreased in the 3 hours, 12 hours, and 36 hours exposure groups decreased significantly (Occludin/β-actin: 0.74±0.17, 0.91±0.20, 0.79±0.23 vs. 1.41±0.08, all P < 0.05). Although the protein expression of Claudin-1 decreased in each exposure group, the difference was not statistically significant. Conclusion:The intestinal injury caused by acute DQ poisoning may be related to the activation of pyroptosis pathway of small intestinal cells and the reduction of the density of intercellular junctions.