Objective To understand the surveillance situation of poliovirus in Guangzhou from 2011 to 2024, and to further strengthen polio surveillance and ensure the continued maintenance of a polio-free status. Methods An analysis was conducted on the discovery and investigation results of six cases of vaccine-derived poliovirus (VDPV) detected in Guangzhou. Results A total of 6 VDPV incidents were reported in Guangzhou from 2011 to June 2024, among which 5 incidents were from sewage sample testing in the Liede Sewage Treatment Plant in Guangzhou, all of which were confirmed as VDPV, with 1 for type I, 1 for type II, and 3 for type III. In addition, one confirmed HFMD case was identified as a type VDPV II carrier. No presence of any wild poliovirus (WPV), VDPV cases, or circulating VDPV (cVDPV) was reported. Conclusion Guangzhou City has maintained a high level of vigilance and effectiveness in the monitoring and prevention of polio. Continuously strengthening the construction of the polio monitoring network, optimizing vaccination strategies, and comprehensively improving public health awareness are still the focus of the prevention and control work in the future.

An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.

Computational approaches, encompassing both physics-based and machine learning (ML) methodologies, have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities. The human dopamine (DA) transporter (hDAT) is the primary therapeutic target of numerous psychiatric medications. However, traditional hDAT-targeting drugs, which interact with the primary binding site, encounter significant limitations, including addictive potential and stimulant effects. In this study, we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape (WHALES) descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs. Initially, WHALES descriptors facilitated a similarity search, employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates. Consequently, from a compound library of 4,921 marketed and clinically tested drugs, we identified 27 candidate atypical inhibitors. Subsequently, ADMETlab was employed to predict the pharmacokinetic and toxicological properties of these candidates, while induced-fit docking (IFD) was performed to estimate their binding affinities. Six compounds were selected for in vitro assessments of neurotransmitter reuptake inhibitory activities. Among these, three exhibited significant inhibitory potency, with half maximal inhibitory concentration (IC₅₀) values of 0.753 μM, 0.542 μM, and 1.210 μM, respectively. Finally, molecular dynamics (MD) simulations and end-point binding free energy analyses were conducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation. In conclusion, our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Objective To explore the genotoxicity of lead on DNA damage and the repair role of homologous recombination repair protein RAD51 in lead-induced DNA double-strand breaks in TK6 cells. Methods i) TK6 cells in the logarithmic growth phase were divided into five groups: blank control group, low-dose group, medium-dose group, high-dose group, and positive control group. The first four groups were treated with lead acetate at concentrations of 0, 120, 240 and 480 μmol/L, respectively. The positive control group was treated with 100 μmol/L hydrogen peroxide solution incubated on ice for 24 hours. After the positive rate of phosphorylated histone H2AX (γ-H2AX) was detected by immunofluorescence. Cell proliferation was detected by 5-ethynyl-2'-deoxyuridine (EDU) method. Cell cycle and apoptosis were detected by flow cytometry, and the relative expression of RAD51 protein was detected by Western blotting. ii) A short hairpin RNA (shRNA) silencing RAD51 model was constructed in TK6 cells, and the cells were divided into untreated group (normal TK6 cells), negative control group (sh-NC), and RAD51 silencing group (sh-RAD51). The mRNA expression of RAD51 was detected by real-time fluorescence quantitative polymerase chain reaction, and the protein expression of RAD51 was detected by Western blotting to verify the interference effect. iii) Normal TK6 cells, sh-NC, and sh-RAD51 were treated with 480 μmol/L lead acetate for 24 hours, and were divided into lead treatment group, lead+negative control group, and lead + RAD51 silencing group, respectively. Untreated normal TK6 cells was served as the control group. The positive rate of γ-H2AX and the expression of RAD51 protein in each group was detected by immunofluorescence and Western blotting, respectively. Results i) With the increase of lead acetate treatment concentration in TK6 cells, the positive rate of γ-H2AX increased (all P<0.05), the proportion of EDU positive cells decreased (all P<0.05), and the proportion of S-phase cells decreased (all P<0.05). The proportion of G1-phase cells in the high-dose group and the positive control group was higher than those in the low- and medium-dose groups (all P<0.05). The proportion of G2-phase cells in the medium-dose group, high-dose group, and positive control group increased compared with the blank control group (all P<0.05), although no significant differences were observed among these three dosing groups (all P>0.05). The apoptosis rate and the relative expression of RAD51 protein of TK6 cells in each group increased with the increase of lead acetate concentration (all P<0.05). ii) The relative expression levels of RAD51 mRNA and protein in the RAD51 silencing group were lower than those in the untreated group and the negative control group (all P<0.05) after RAD51 silencing. iii) The positive rate of γ-H2AX in the lead + RAD51 silencing group increased (all P<0.05), and the relative expression of RAD51 protein decreased (all P<0.05),compared with the control group, lead treatment group, and lead + negative control group. Conclusion Lead exposure induces DNA double-strand breaks in TK6 cells, inhibits cell proliferation, and causes cell cycle arrest and apoptosis in a dose-effect manner. Downregulation of the RAD51 gene can lead to inhibition of the homologous recombination repair pathway, thereby increasing the TK6 cell sensitivity to lead-induced DNA damage.

Objective To analyze the clinical characteristics,drug resistance and risk factors for poor prognosis in children patients with carbapenem resistant Klebsiella pneumoniae(CRKP)infection.Methods The samples of CRKP isolated from the children inpatients in this hospital from August 5,2016 to December 31,2020 were collected.The clinical data and drug resistance of CRKP in the patients with CRKP positive were analyzed.The risk factors in the poor prognosis group and good prognosis group of children pa-tients with CRKP infection conducted the correlation analysis.Results A total of 106 strains of non-repeti-tive CRKP were collected,which were mainly isolated from the patients ≤ 1 year old.The department distri-bution was dominated by the neonatal ICU and comprehensive ICU.CRKP showed the high resistance to mul-tiple antibacterial drugs,and its resistance rates to amikacin,levofloxacin,gentamicin,ciprofloxacin,minocy-cline and chloramphenicol were less than 30％.The poor prognosis rate in the children patients with CRKP in-fection reached 27.4％.The logistic multivariate regression analysis results showed that the multiple organ dysfunction and anemia were the independent risk factors for poor prognosis in the children patients with CRKP infection(P＜0.05).Conclusion The children CRKP infection is mainly the infants ≤1 years old,and CRKP shows the high resistance to multiple antibacterial drugs,the independent risk factors of poor prognosis include the multiple organ dysfunction and anemia

ObjectiveTo study the effect of Qizhu Kang'ai prescription （QZAP） on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 （PCK1） in the liver of mouse model of liver cancer induced by diethylnitrosamine （DEN） combined with carbon tetrachloride （CCl₄） and Huh7 cells of human liver cancer， so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl₄ was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group， a model group， and a QZAP group were set up， in which QZAP （3.51 g·kg^-1） or an equal volume of normal saline was administered daily by gavage， respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyltransferase （γ-GT）， and alpha-fetoprotein （AFP） in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment， Huh7 cells were divided into blank group， QZAP low， medium， and high dose groups and/or PCK1 inhibitor （SKF-34288 hydrochloride） group， and Sorafenib group. The corresponding drug-containing serum and drug treatment were given， respectively. Cell counting kit-8 （CCK-8） method， colony formation experiment， Edu fluorescent labeling detection， intracellular adenosine triphosphate （ATP） content detection， and cell cycle flow cytometry detection were used to evaluate the proliferation ability， energy metabolism changes， and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1， serine/threonine kinase （Akt）， phosphorylated Akt （p-Akt）， and cell cycle-dependent protein kinase inhibitor 1A （p21）. ResultCompared with the model group， the pathological changes such as cell atypia， necrosis， and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated， and the number of liver tumors was reduced （P<0.01）. The serum ALT， AST， γ-GT， and AFP levels were reduced （P<0.01）. At the cell level， compared with the blank group， low， medium， and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells （P<0.01） and the number of positive cells with Edu labeling （P<0.01） and inhibit clonal proliferation ability （P<0.01）. The QZAP groups could also reduce the intracellular ATP content （P<0.05） and increase the distribution ratio of the G₀/G₁ phase of the cell cycle （P<0.05） in a dose-dependent manner. Compared with the model group and blank group， PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced （P<0.05，P<0.01）， and the p-Akt protein level was significantly increased （P<0.01）. Compared with the blank group， the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased （P<0.05）， but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G₀/G₁ phase distribution. Compared with the SKF-34288 hydrochloride group， the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content， cell survival rate， and Edu-positive cell ratio of Huh7 cells （P<0.05） and significantly increased the G₀/G₁ phase distribution proportion （P<0.05）. ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression， thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.

Objective: To explore the impact of online sexuality education courses on the sexual knowledge, attitudes and related behaviors of rural girls, so as to provide the practical guidance for promoting sexual health and development. Methods: From February to June 2023, by posting information online and through commonweal organization websites, rural primary schools in 12 provinces were recruited for a semester of online sexuality education courses from October to November 2023. A self compiled sexuality education questionnaire was used to survey the knowledge, attitudes, and behaviors of rural girls before and after the course intervention, with pre tests in September 2023 and post tests in December 2023. The eligible samples were 3 058 and 2 602 , respectively. Independent sample t tests and text frequency and sentiment analysis were used to process the data Results: In terms of sexual knowledge, the scores of rural girls before and after the test were (8.49±3.29) and (9.40±3.35), respectively, with the post test score being higher than the pre test ( t =-10.20, P <0.01). In terms of attitudes, the scores of rural girls before and after the test were (11.50±4.62) and (10.82±4.80), respectively, with a decrease in stigmatization towards physiological development in the post test ( t =5.40, P <0.01). Regarding sexual related behaviors, the frequency of sexualbased bullying among rural girls was (5.12±2.13) before and (4.89±2.18) after, with a statistically significant difference ( t =3.99, P <0.01). The frequency and willingness of rural girls to discuss sexual topics with significant others both increased on post test (pre test:8.45±2.62; post test: 8.73± 2.62) and (pre test:8.90±2.46, post test:9.16±2.46), with a statistically significant difference ( t =-3.91, -4.03, P < 0.01 ). Text analysis revealed that "boys" "girls" and "menstruation" were the most concerned topics among the participants, and compared to before receiving sex education (69.91%), the proportion of negative emotions among rural girls decreased ( 18.59 %). Conclusion Online sexuality education courses can improve the sexual knowledge of rural girls, reduce stigma and negative emotions towards sex, decrease the incidence of sexual based bullying and increase the frequency and willingness to discuss sexual topics with parents, teachers, and peers.

ObjectiveTo investigate the relationship between mosquito density fluctuations and meteorological factors, so as to provide a scientific basis for mosquito surveillance analysis, risk assessment, and comprehensive prevention and control. MethodsMosquito surveillance and monitoring data of 2020‒2023 was obtained from on-site supervisory sampling by Songjiang Center for Disease Control and Prevention, and meteorological data was obtained from the Wheat A wheat malt-agro-meteorological big data system. Excel 2019 and SPSS 25.0 software were used to organize and analyze the mosquito number, species composition, and seasonal changes in mosquito density captured by the CO₂-light trap at rach monitoring site. Circular distribution method was used to calculate the peak time of mosquito density, combined with the meteorological data of the same period to explore the impact of meteorological factors on the results of mosquito surveillance. ResultsThere was a statistical difference in the overall distribution of mosquito quantity in different habitats(H=23.11, P<0.05), 2020‒2023. In addition, the results showed that July 28th was the peak day for mosquito density, and the duration from June 13th to September 11th was the seasonal peak period for mosquitoes. Pearson correlation analysis showed a positive correlation between mosquito density and average air temperature, average highest air temperature, average lowest air temperature, extreme maximum air temperature, extreme minimum air temperature, precipitation, and number of precipitation days (all P<0.01). While, there was no significant correlation between average wind speed and mosquito density (P>0.05). Multiple stepwise regression analysis resulted in the equation of Y=0.151X_{extreme minimum temperature}+0.321X_{number of precipitation days}+1.002X_{SQRT precipitation}-1.288 (F=102.635, P<0.05). ConclusionThe CO₂-light trap is advisable to monitor the habitats of farmers, livestock sheds, residential areas, parks, hospitals, and other external environments. Air temperature and precipitation have a significant impact on mosquito density. It is recommended to implement comprehensive prevention and control measures to reduce mosquito density and prevent mosquito-borne diseases before the peak period of mosquitoes.

[摘 要] 无义介导的mRNA降解（NMD）作为一种质量控制机制，可降解含有过早终止密码子（PTC）的异常mRNA，参与生长发育、调节免疫功能，且与肿瘤微环境密切相关。NMD对肿瘤有抑制或促进的双重作用：一方面，NMD通过下调促癌蛋白表达、抑制促癌信号通路和应激微环境等途径抑制肿瘤进展；另一方面，NMD通过抑制抑癌基因的表达、癌细胞凋亡和肿瘤新抗原的产生促进肿瘤进展。此外，NMD并非降解所有携带PTC的mRNA，PTC出现的位置可能决定NMD触发或逃逸，由于各基因的高频突变区域各不相同，因此不同基因发生PTC突变后是否触发NMD则具有不同的倾向性。随着二代测序技术的成熟与普及，基因突变筛查已成为临床诊疗常规手段，这使得从多基因层面探究NMD的规律与意义成为可能。因此，在进一步了解NMD的功能及其机制的基础上，通过高通量测序与计算机算法评估NMD水平，有望在临床工作中扬长避短地发挥NMD潜在的临床价值，助力个性化临床诊治与精准医疗的发展。

Objective To evaluate the accuracy of selective laser melting of cobalt-chromium(CoCr)clasps with different build angles and support densities.Methods The 3D software constructed a sample clasp(reference object)with an undercut depth of 0.50 mm,which was then imported to a metal 3D printer to form CoCr clasps at different build angles(0°,45°,and 90°)and support densities(0.50,0.70,0.90,and 1.10 mm).A model scanner was used to obtain scans of all clasps(test objects);the test objects were aligned with the reference object and test subjects were aligned with each other through a best-fit alignment method using Geomagic software to obtain root mean square error(RMSE)values for the accuracy of the clasps.The data were statistically analyzed using one-way analysis of variance or non-parametric rank sum test(α=0.05).Results In terms of trueness,the different build angle groups with support density of 0.50 mm were ranked by RMSE values as follows:90°group>0°group>45°group.For the different build angle groups with support densities of 0.70,0.90,and 1.10 mm,the RMSE values ranked as follows:45°group>90°group>0°group.In terms of precision,the different build angle groups with support density of 0.50 mm were ranked by RMSE values as follows:90°group>0°group>45°group.For support density of 0.70 mm,the ranking was 90°group>45°group>0°group,while for support densities of 0.90 and 1.10 mm,the ranking was 45°group>90°group>0°group.Conclusion The accuracy of CoCr clasps varies with the build angle and support density.However,clasps produced at a build angle of 0°and a support density of 0.90 mm exhibit higher accuracy and are recommended for use in clinical and technical laboratories.