To investigate the effect of baicalin (BAI)-loaded cross-linked lipoic acid nanocapsules (BAI@cLANCs) against hydrogen peroxide (H2O2)-induced senescence in human umbilical vein endothelial cells (HUVECs), this study examined the toxicity of BAI@cLANCs on HUVECs by MTT method. The cell nuclear staining, SA-β-gal staining, and MTT methods were used to assess the optimal concentration of H2O2-induced senescence in HUVECs. The cellular uptake of BAI@cLANCs was evaluated using fluorescence microscopy imaging and flow cytometry. The proportion of cellular senescence was determined by SA-β-gal staining. The level of reactive oxygen species (ROS) in senescent cells was detected by fluorescence microscopy imaging and multifunctional microplate reader. The content of malondialdehyde (MDA) in cells was detected by lipid oxidation detection kit, and the cell cycle was analyzed by flow cytometry with propidium iodide staining. The results showed that BAI@cLANCs had no significant effect on the growth of HUVECs in the range of BAI at 2.80−112 mmol/L. 200 μmol/L and 25 minutes were the ideal conditions for H2O2-induced senescence of HUVECs. cLANCs as drug delivery carriers significantly enhanced the uptake efficiency of BAI in HUVECs. Compared with the normal group, the H2O2 model group showed decreased cell viability, increased positive SA-β-gal staining rate, increased ROS and MDA content, as well as increased percentage of cells blocked in S phase and decreased cells entering G2/M phase. Compared with the H2O2 model group, BAI, cLANCs, BAI + cLANCs, and BAI@cLANCs groups showed increased cell viability, decreased positive SA-β-gal staining rate, decreased ROS and MDA content, decreased percentage of S-phase cells, and increased cells entering G2/M phase, with the best anti-aging effect in the BAI@cLANCs group. In summary, the results above showed that both BAI and cLANCs have anti-aging properties. With cLANCs as drug carriers, the anti-aging benefits of BAI@cLANCs are synergistic and can effectively delay H2O2-induced senescence of HUVECs.

ObjectiveTo analyze the changes in the degree of coordination of China's major epidemic prevention and control efforts before and after the outbreak of the Corona Virus Disease 2019 (COVID-19), so as to explore the impact of epidemic prevention and control measures on coordination dynamics. MethodsA total of 3 864 policy documents related to epidemic prevention and control from January 2000 to December 2020 across 31 provinces (autonomous regions, and municipalities) in China were systematically collected. Contents specific to collaborative and cooperative efforts were extracted, and the extent of interdepartmental coordination were quantified to assess the effectiveness of epidemic prevention and control efforts. Wilcoxon signed-rank test was adopted to statistically analyze the differences between the indicators before and after the epidemic. ResultsThe average overall coordination level for major epidemic prevention and control in 31 provinces (autonomous regions, and municipalities) increased from 43.06% to 97.62%, and the average coordination levels in the eastern, central, and western China soared from 42.29%, 37.50%, and 47.46%, to 98.81%, 96.20%, and 97.46%, respectively, with statistically significant differences (all P<0.05). In terms of department categorization, coordination levels in the professional departments and the key support departments peaked at 100.00%, while other support departments rose to 95.43%, with an increase of 77.15%, 181.85%, and 139.89%, respectively, exhibiting noteworthy statistically significant differences (all P<0.001). ConclusionThe scope of coordination departments of China’s major epidemic prevention and control exists a remarkable surge following the COVID-19 outbreak, notable heightened coordination is particularly observed among the key support departments. Future endeavors should prioritize the roles played by diverse departments in epidemic prevention and control, enhancing both the clarity of departmental responsibilities and the effectiveness of interdepartmental coordination.

ObjectiveTo systematically evaluate the public health governance capacity of 40 cities in Jiangsu, Zhejiang, and Anhui Provinces, providing a scientific evaluation basis for building a "Healthy Yangtze River Delta". MethodsA comprehensive collection of policy documents, public information reports, and research literature related to public health governance capacity in Jiangsu, Zhejiang, and Anhui Provinces was conducted, totaling 6 920 policy documents, 1 720 information reports, and 1 200 literature pieces. Based on the evaluation standards for an appropriate public health system established by the research team, the basic status of public health governance capacity was assessed to identify the strengths and weaknesses of the 40 cities. ResultsIn 2022, the public health governance capacity score for the 40 cities in Jiangsu, Zhejiang, and Anhui Provinces was (562.5±38.0) points. In terms of specific areas, the emergency response field received the highest score of (791.4±49.7) points, while the chronic disease prevention and control field received the lowest score of (368.2±29.6) points. The Jiangsu-Zhejiang-Anhui region has largely achieved the strategic priority of health, gradually improved public health legal regulations, and established a basic organizational framework with a solid foundation for information and data infrastructure. However, challenges still need to be addressed, such as unstable government funding for public health, unclear departmental responsibilities, and barriers to information interoperability. ConclusionThe public health governance capacity of the 40 cities in Jiangsu, Zhejiang, and Anhui Province has been at a moderate level, but disparities have still existed across regions and fields. In the future, while continuing to deepen existing advantages, it is essential to accurately identify the causes of problems, establish a long-term and stable investment mechanism, enhance information connectivity mechanisms, further clarify departmental responsibilities, and promote the achievement of the "Healthy Yangtze River Delta" goal.

ObjectiveTo investigate the effects of Scutellariae Radix combined with epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） on cell proliferation， apoptosis， cancer stem cell （CSC） marker expression， and metabolism in non-small cell lung cancer （NSCLC） cells. MethodsThe anti-tumor effects of Scutellariae Radix and EGFR-TKIs （gefitinib or osimertinib） in NSCLC cells were evaluated using the cell counting kit-8 （CCK-8） and Annexin V-FITC/propidium iodide （PI） double staining apoptosis assay. The activity of Scutellariae Radix and EGFR-TKIs in three-dimensional （3D） cultures of NSCLC cells was assessed using the CellTiter-Glo® 3D cell viability assay. The mRNA and protein expression levels of CSC markers， sex determining region y box protein 2 （SOX2） and aldehyde dehydrogenase 1 family member A1 （ALDH1A1）， were detected by quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot， respectively. Changes in intracellular reactive oxygen species （ROS） levels were detected by ROS staining， and the redox ratio was detected by femtosecond laser labeling free imaging （FLI）. ResultsUnder both two-dimensional （2D） and 3D culture conditions， compared with the blank group and EGFR-TKI group， the combination group showed significantly reduced cell viability and increased apoptosis rate （P<0.05）. Compared with the EGFR-TKI group， the mRNA and protein levels of CSC markers were significantly downregulated in the combination group （P<0.05）. Additionally， the redox ratio was significantly elevated （P<0.05）， and ROS levels were also increased in the combination group compared with the EGFR-TKI group. ConclusionIn NSCLC cells， Scutellariae Radix enhances the redox ratio and increases ROS levels， thereby inhibiting the expression of CSC markers and strengthening the anti-tumor effects of EGFR-TKIs. This provides a novel molecular mechanism by which Scutellariae Radix may enhance the sensitivity of targeted therapies.

Objective:To study the early predictors of refractory septic shock (RSS) in neonates.Methods:From July 2020 to December 2021, clinical data of neonates with septic shock admitted to the Neonatal Department of our hospital were retrospectively reviewed. According to the maximum septic shock score (SSS) during clinical course, the neonates were assigned into RSS group and non-RSS group. Perinatal data, laboratory results and hemodynamic parameters at diagnosis were compared between the two groups. Multiple logistic regression analysis was used to identify independent risk factors of RSS and septic shock-related death. Receiver operating characteristic (ROC) curve was constructed to evaluate the early predictors of poor prognosis.Results:A total of 130 neonates were enrolled, including 54 in RSS group and 76 in non-RSS group. Compared with the non-RSS group, the RSS group had significantly lower pH, base excess (BE), stroke volume index (SVI), cardiac output (CO) and cardiac index (CI).Meanwhile, the RSS group had significantly higher mean arterial pressure (MAP) to CI ratio (MAP/CI) and SSS [including bedside SSS (bSSS), computed SSS (cSSS) and modified version of cSSS (mcSSS)] (all P<0.05). Multiple logistic regression analysis showed that increased MAP/CI was an independent predictor of RSS. The cut-off value of MAP/CI was 11.6 [sensitivity 62%, specificity 87%, positive predictive value (PPV) 79% and negative predictive value (NPV) 77%], with an area under the curve (AUC) of 0.734. Increased mcSSS was an independent predictor of septic shock-related death. The cut-off value of mcSSS was 5.8 (sensitivity 83%, specificity 72%, PPV 21% and NPV 97%), with an AUC of 0.845. Conclusions:Increased MAP/CI (≥11.6) and mcSSS (≥5.8) may be early predictors of RSS and septic shock-related death in neonates.

Objective This study aimed to observe the effect of Jiang Tang San Hao Formula(JTSHF)on systemic and intestinal inflammation,as well as on the NLRP3 inflammasome in type 2 diabetic mice(T2DM),and to elucidate its anti-diabetic molecular mechanisms.Methods Four-week-old male C57BL/6 N mice were used to establish the T2DM model using a high-fat diet combined with streptozotocin injection.The diabetic mice were randomly divided into the model,metformin,and JTSHF groups.A control group was also set to provide baseline comparisons.Each group of mice was orally administered with the corresponding medication daily.The metformin group was orally administered with 0.20 g/kg metformin,the JTSHF group was orally administered with 4.26 g/kg JTSHF,and the control group and model group were orally administered with an equal amount of sterile water continuously for 8 weeks.After an 8-week drug intervention via gavage,the lipopolysaccharide(LPS),tumor necrosis factor-alpha(TNF-α),interleukin 1 beta(IL-1β),and interleukin 6(IL-6)serum and colon levels were quantified using an enzyme-linked immunosorbent assay(ELISA).The pathological morphology of the colon was observed using hematoxylin and eosin staining.NOD-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),caspase-1,zonula occludens-1(ZO-1),occludin,and G-protein coupled receptor 43(GPR43)protein expression in the colon were assessed using immunohistochemistry.The mRNA expression levels of NLRP3,ASC,caspase-1,ZO-1,Occludin,and GPR43 in the colon were detected using Real-time PCR.Results The ELISA data revealed significant differences in inflammatory markers among the groups.Compared with the model group,the JTSHF group exhibited notably reduced LPS,TNF-α,IL-1β,and IL-6 levels(P<0.05).Moreover,compared with the model group,JTSHF treatment upregulated ZO-1,occludin,and GPR43 protein and mRNA expression in the colon and downregulated NLRP3,ASC,and Caspase-1 protein and mRNA expression(P<0.05).Conclusion The inflammatory reaction of T2DM mice is apparent.JTSHF effectively alleviates the systemic and intestinal inflammatory response of T2DM mice by inhibiting the NLRP3 inflammasome and repairing the intestinal mucosal barrier,highlighting the potential molecular mechanisms of the anti-diabetes effects of JTSHF.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

Objective To investigate the prevalence of Echinococcus infections in small rodents around human residential areas in Yushu City, Qinghai Province in 2023, so as to provide insights into precision echinococcosis control. Methods One or two quadrats, each measuring 50 m × 50 m, were randomly assigned in Shanglaxiu Township and Longbao Township, Yushu City, Qinghai Province on June 2023, respectively, and 300 plate-type mouse traps, each measuring 12.0 cm × 6.5 cm, were assigned in each quadrat. Small rodents were captured during the period between 10 : 00 and 18 : 00 each day for 4 days. Then, all captured small rodents were identified and dissected, and liver specimens with suspected Echinococcus infections were subjected to pathological examinations. The Echinococcus cytochrome c oxidase 1 (cox1) gene was amplified using PCR assay, and the sequence of the amplified product was aligned to that was recorded in the GenBank to characterize the parasite species. In addition, a phylogenetic tree of Echinococcus was generated based on the cox1 gene sequence using the neighbor-joining method. Results A total of 236 small rodents were captured in Shanglaxiu and Longbao townships, Yushu City, including 65 Qinghai voles and 51 plateau pikas in Shanglaxiu Township, and 62 Qinghai voles and 58 plateau pikas in Longbao Township, and there was no significant difference in the constituent ratio of small rodents between the two townships (χ² = 0.294, P > 0.05). Seven plateau pikas and 12 Qinghai voles were suspected to be infected with Echinococcus by dissection, and pathological examinations showed unclear structure of hepatic lobules and disordered hepatocyte arrangement in livers of small rodents suspected of Echinococcus infections. PCR assay identified E. shiquicus DNA in 7 Qinghai voles, which were all captured from Shanglaxiu Township. Phylogenetic analysis showed that the cox1 gene sequence of Echinococcus in small rodents was highly homologous to the E. shiquicus cox1 gene sequence reported previously. Conclusion Plateau pika and Qinghai vole were predominant small rodents around human residential areas in Yushu City, Qinghai Province in 2023, and E. shiquicus infection was detected in Qinghai voles.

Objective　To explore the characteristics of toxic heavy metal pollution in atmospheric PM2.5 (Particulate matter 2.5) during winter in Nanning City and to evaluate the health risks for the population. Methods　Atmospheric PM2.5 samples were continuously collected in the urban areas of Nanning from January to February 2019. The concentrations of seven toxic heavy metals, including cadmium (Cd), arsenic (As), chromium (Cr), lead (Pb), nickel (Ni), mercury (Hg), and manganese (Mn) in atmospheric PM2.5 were analyzed by X-ray fluorescence spectrometry. The pollution characteristics of toxic heavy metals were studied by geo-accumulation index and enrichment factor methods, and their health risks to children and adults were assessed using the health risk assessment model of the United States Environmental Protection Agency. Results　The mass concentration of atmospheric PM2.5 in Nanning in winter 2019 was (44±29) μg/m3, which was generally at a low level. Different degrees of pollution were found for Hg, Cd, As, Cr, and Pb in PM2.5, with Hg and Cd being more seriously polluted. Hg and Cd were highly enriched in PM2.5, followed by Pb with moderate enrichment. These three elements mainly originated from man-made pollution. As, Cr and Ni were mildly enriched and affected by both natural and anthropogenic sources. The non-carcinogenic risks were in the order of As>Pb>Hg>Cr>Cd>Mn>Ni. The total non-carcinogenic risks for the three populations were all less than 1, which is within acceptable limits. The carcinogenic risks were ranked as Cr>As>Cd>Ni, with Cr, As, and Cd posing carcinogenic risks to children and adults ranging from 1×10-6 to 1×10-4. Moreover, the total carcinogenic risks of heavy metals (Cr, As, Cd, and Ni) were higher than 1×10-4 for children, indicating a potential carcinogenic risk. Conclusions　The mass concentration of PM2.5 and heavy metal elements in Nanning City during the winter of 2019 was relatively low, but the pollution of heavy metals still exists. The non-carcinogenic risk of heavy metals is within an acceptable range, but the carcinogenic risk poses a potential danger to children.

Background and purpose:Rectal cancer is one of the malignant tumors that seriously harm human health in the world,ranking third in incidence and second in mortality.With the development of social and economic level,the incidence and mortality of colorectal cancer in China are increasing,and China becomes one of the countries with high incidence of colorectal cancer disease in the world.The recommended treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy combined with surgery,which greatly improves the prognosis of patients.However,intestinal adverse reactions such as diarrhea caused by neoadjuvant chemoradiotherapy are increased,and some patients are forced to delay or interrupt treatment due to serious side effects.Amifostine is a broad-spectrum normal cell protective agent,which has good protective effect against various radiochemotherapy toxicity.We conducted a retrospective analysis of patients with locally advanced rectal cancer who received neoadjuvant radiotherapy combined with irinotecan concurrent chemotherapy to investigate whether concurrent use of amifostine alleviated gastrointestinal and hematological toxicities.Methods:A retrospective cohort analysis was used in this study.Clinical data of patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy at the Affiliated Cancer Hospital of Fudan University during the period of discharge from January 1,2018 to December 31,2019 were retrospectively collected.The patients were divided into 2 groups by whether amifostine was used during the same period.The main purpose of the study was to analyze whether amifostine can reduce gastrointestinal and hematological toxicities,and secondary objectives included whether amifostine could alter tumor marker levels,mesorectal fascia invasion(MRF)positive rate,extramural vascular invasion,positive rate of EMVI and pathological complete response(pCR).Using SAS9.4 statistical software,the normality test was carried out for continuous variables.The rank sum test of Wilcoxon was performed when the diarrhea grade did not conform to normal distribution.Analysis of variance was performed for intra-group comparison,and Wilcoxon rank sum test was performed for inter-group comparison.Because of the imbalance between groups,the difference between the two groups was compared using a generalized linear model.This study strictly followed the STrengthening the Reporting of OBservational studies in Epidemiology(STROBE)guidelines to ensure the transparency of the research methodology and the reliability of the results.Results:Finally,154 eligible patients were included,of whom 78 were in the amifostine group and 76 were in the control group.The highest grade of diarrhea in amifostine group was 1.00(1.00,1.00),lower than that in control group(2.00,3.00),and the difference between groups was statistically significant(P＜0.01).After radiotherapy,white blood cell count(WBC),hemoglobin(HB)and absolute neutrophil count(ANC)from the two groups were obtained.ANC and platelet count(PLT)showed no statistically significant difference(P＞0.05),and the lowest values of WBC,RBC and PLT did not have statistically significant difference between the two groups during neoadjuvant period(P＞0.05).Amifostine may not alleviate hematological toxicity.Carbohydrate antigen 72-4(CA72-4)(Z=2.22,P=0.03),carbohydrate antigen 50(CA50)(Z=-2.49,P=0.01)and carbohydrate antigen 24-2(CA24-2)had statistically significant difference(Z=-2.29,P=0.02).There were no significant differences in MRF positive rate(P=0.11),EMVI positive rate(P=0.61)and pCR rate(P=0.94)between the two groups.Conclusion:Concurrent administration of amifostine in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy can reduce gastrointestinal toxicity and reduce the levels of tumor markers CA72-4,CA50 and CA24-2.However,it may have no significant effect on improving hematological toxicity,MRF and EMVI positive rate and pCR rate.