OBJECTIVE To establish a method for simultaneous determination of 7 anti-tumor drugs （irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate） in human plasma and apply it to the clinic. METHODS After precipitating with a methanol-acetonitrile mixture （1∶ 1， V/V） containing 0.1% formic acid， liquid chromatography-tandem mass spectrometry （LC-MS/MS） was used to determine the plasma concentration， using deuterium isotopes of each analyte as internal standards. The chromatography was performed on the Agilent Eclipse Plus C18 column with a gradient elution of water （containing 0.1% formic acid+0.04% 5 mmol/L ammonium formate） as mobile phase A and acetonitrile （containing 0.1% formic acid） as mobile phase B. The flow rate was 0.6 mL/min， and the column temperature was set at 40 ℃ . The sample size was 10 μL， and the analysis lasted for 5.5 min. Electrospray ionization was used in positive and negative ion mode， and multiple reaction monitoring mode was used. The ion pairs used for quantitative analysis were m/z 587.1→167.1 （irinotecan）， m/z 360.1→244.1 （capecitabine）， m/z 876.4→308.0 （paclitaxel）， m/z 830.3→304.2 （docetaxel）， m/z 372.1→129.1 （tamoxifen）， m/z 284.1→242.1 （letrozole）， and m/z 455.0→ 308.0 （methotrexate）. A total of 97 patients with malignant tumors in our hospital were selected to measure the plasma concentrations of 7 anti-tumor drugs using the above method. RESULTS The linear ranges of irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate were 2-1 000 ng/mL （r＝0.994 3）， 20-10 000 ng/mL （r＝0.997 5）， 2-1 000 ng/mL （r＝0.997 9）， 1-500 ng/mL （r＝0.995 8）， 1-500 ng/mL （r＝0.995 2）， 1-500 ng/mL （r＝0.996 4）， 10-5 000 （r＝0.997 7）， respectively. The quantitative lower limits were 2， 20， 2， 1， 1， 1 and 10 ng/mL； RSDs of intra-assay precision were 0.08%-14.86% （n＝6）. RSDs of inter-batch precision were 1.51%-11.55% （n＝3）， and the accuracies were 89.17%-114.93% （n＝6）. The matrix effects ranged from 89.89%-119.74% （n＝6）. RSDs of the stability tests were 1.98%-14.88% （n＝6）. The results of E-mail：hangpengzhou@163.com clinical application showed， the average plasma concentrations of irinotecan， capecitabine， paclitaxel and docetaxel were 704.09， 909.40， 36.45， 150.43 ng/mL， respectively. The values of the coefficient of variation were 25.24%， 62.65%， 122.69%， and 92.27%. CONCLUSIONS The established LC-MS/MS method is simple and rapid， and can be used for the simultaneous determination of 7 commonly used anti-tumor drugs in the plasma of patients with malignancy.

Background Injury poses a serious threat to human health. As global warming continues to intensify, there is an urgent need to explore the impact of temperature changes on injury deaths. However limited research has focused on this issue. Objective To investigate the relationship between daily mean temperature change (Tm) and injury death, as well as to estimate the associated future death burden in Hunan Province. Methods We employed an individual-level, time-stratified case-crossing design to establish a conditional logistic regression model to analyze the exposure-response relationship between daily mean temperature change and injury death in Hunan Province from 2013 to 2018. Consequently, we conducted subgroup analysis of gender, age group, and injury type. Finally, we estimated the excess burden of injury death attributable to temperature changes under a sustainable development path [low emission scenario (SSP1-2.6)], regional competition path [high emission scenario (SSP3-7.0)], or fossil fuel development path [very high emission scenario (SSP5-8.5)]. Results The study collected 155577 injury deaths in Hunan Province. The results indicated that for each 1 ℃ increment in daily mean temperature, the cumulative excess risk (CER) of injury mortality among Hunan residents increased by 0.71% (95%CI: 0.53%, 0.90%). Notably, the CER for intentional injuries (1.06%, 95%CI: 0.51%, 1.61%) was higher than that for unintentional injuries (0.66%, 95%CI: 0.46%, 0.87%). Warmer temperatures were positively associated with CER of mortality due to drowning, falls, transport injuries, assaults, and suicides, while they were negatively associated with mortality due to poisoning. Compared with 2010–2019, for 2090–2099, the excess mortality rate (EMR) due to ambient temperature increase in Hunan Province under the SSP5-8.5 scenario (14.62/100000, 95%CI: 10.81/100000, 18.40/100000) would be higher than that of the SSP3-7.0 scenario (10.28/100000, 95%CI: 7.58/100000, 12.97/100000) and the SSP1-2.6 scenario (3.35/100000, 95%CI: 2.46/100000, 4.23/100000); the EMR would be around 2.5 times among men (20.64/100000, 95%CI: 14.44/100000, 26.8/100000) than that among women (8.33/100000, 95%CI: 3.98/100000, 12.6/100000). Among unintentional injuries, the leading contributors to EMR would be drowning (4.46/100000), falls (3.96/100000), and transport injuries (2.96/100000). And among intentional injuries, the EMR for suicide (2.08/100000) would be higher than that for assault (0.47/100000). Conclusion Climate warming will increase the total burden of injury-related deaths among residents in Hunan Province, especially in the absence of effective mitigation strategies and measures. It is necessary to strengthen the prevention and control of severe injuries closely related to temperature changes, such as drowning, falls, traffic, and suicides injuries, in order to reduce injury deaths associated with climate change.

Background Under the background of global warming, research on association between ambient temperature and risk of injury is needed. Objective To examine the effect of temperature on injury in Bao'an district, Shenzhen and identify the sensitive population, thereby providing a scientific basis for formulating prevention and control strategies and measures of injury. Methods The injury reports from the Injury Surveillance System and the meteorological data of Bao'an District between 2018 to 2022 were collected. The meteorological data were sourced from the fifth generation of the European Centre for Medium-Range Weather Forecasts (ECMWF) land reanalysis data. Based on time-stratified case-crossover design, conditional logistic regression combined with distributed lag nonlinear model was used to evaluate the exposure-response association between ambient temperature and injury. The stratified analyses were further conducted by gender, age, and causes of injury. Results A total of 156205 injury cases were collected from the injury surveillance sentinel hospitals in Bao'an District of Shenzhen from 2018 to 2022, and the median of daily average temperature during the same period was 20.0 ℃. The exposure-response curve showed that the risk of injury was positively correlated with temperature. The linearized analysis revealed that each 1°C increase in temperature was associated with a 1.05% (95%CI: 0.68%, 1.42%) rise in injury risk (ER). Notably, the effect was greater in females (ER=1.31%, 95%CI: 0.67%, 1.94%) than males (ER=0.92%, 95%CI: 0.47%, 1.37%). Among age groups, adults ＞60 years faced the highest risk (ER=1.91%, 95%CI: −0.36%, 4.24%). The top three temperature-associated injury risks were sharp instrument injuries (ER=2.19%, 95%CI: 1.16%, 3.22%), animal injuries (ER=1.71%, 95%CI: 0.86%, 2.56%), and blunt injuries (ER=071%, 95%CI: −0.08%, 1.51%). The impact of temperature on unintentional injuries (ER=1.11%, 95%CI: 0.72%, 1.49%) was higher than that on intentional injuries (ER=0.43%, 95%CI: −0.85%, 1.72%). Severe injuries (ER=2.20%, 95%CI: −3.09%, 7.77%) were more affected by temperature than mild injuries (ER=1.00%, 95%CI: 0.58%, 1.43%) and moderate injuries (ER=1.15%, 95%CI: 0.42%, 1.89%). Conclusion The increase in ambient temperature associates with injury occurrence, and the impact of temperature exhibits obvious heterogeneity among different populations, indicating that targeted intervention measures should be taken for different populations and types of injuries.

ObjectiveThis study aims to observe the clinical effect of Danggui Liuhuang Tang （DGLHT） on patients with type 2 diabetes mellitus （T2DM） complicated by atherosclerotic cardiovascular disease （ASCVD） at high risk， focus on evaluating the influence of DGLHT on cardiovascular risk indicators such as flow-mediated dilation （FMD）， atherogenic index of plasma （AIP）， and triglyceride-glucose index （TyG）， and explore the regulatory effect of DGLHT on the myeloid differentiation factor 88/nuclear factor-kappa B （MyD88/NF-κB） signaling pathway. MethodsThe clinical study was a single-center， double-blind， and randomized controlled trial. A total of 68 patients with T2DM-ASCVD at high risk for cardiovascular events with Yin deficiency and fire excess syndrome were enrolled and randomly assigned to a treatment group and a control group. The treatment group was given atorvastatin calcium tablets and DGLHT， while the control group was given atorvastatin calcium tablets and placebos. The treatment course was 12 weeks， with a final study completion of 30 patients in the treatment group and 29 in the control group. Changes in cardiovascular risk indicators such as FMD， AIP， TyG， and small dense low-density lipoprotein cholesterol （sdLDL-C） index were compared. Human umbilical vein endothelial cells （HUVECs） were used to establish a vascular endothelial injury and inflammation model. The protective effect of DGLHT on endothelial injury was verified by reverse transcription polymerase chain reaction （Real-time PCR） and Western blot . ResultsAfter 12 weeks of treatment， the AIP in the treatment group significantly decreased compared with that before the treatment （P<0.05）. Compared with the control group， the treatment group showed significant improvements in FMD and TyG （P<0.05）. Additionally， the treatment group demonstrated significant reductions in two-hour postprandial glucose （2 hPG）， glycated albumin （GA）， triglycerides （TG）， apolipoprotein E （Apo E）， and sdLDL-C （P<0.05）. Analysis of traditional Chinese medicine （TCM） syndrome efficacy indicated that in the treatment group， Yin deficiency and fire excess syndromes， including dry throat and mouth （P<0.05）， excessive thirst （P<0.01）， tidal fever and night sweats （P<0.05）， and dry stools （P<0.05）， improved. Compared with the control group， the treatment group showed significant improvements in symptoms of dry throat and mouth （P<0.05） and excessive thirst （P<0.01）. TCM syndrome scores significantly decreased （P<0.01）， and the overall efficacy rate was 56.67%， significantly higher than the 10.34% observed in the control group （P<0.01）. At the cellular level， increasing concentrations of DGLHT led to decreased messenger ribonucleic acid （mRNA） levels of pro-inflammatory cytokines interleukin-6 （IL-6）， tumor necrosis factor-alpha （TNF-α）， and interleukin-1-beta （IL-1β） in lipopolysaccharide （LPS）-stimulated HUVECs （P<0.01）， with significant reductions in the high-concentration group （P<0.01）. DGLHT may inhibit the expressions of MyD88 and phosphorylated （p）-NF-κB p65 proteins in a concentration-dependent manner. ConclusionDGLHT shows significant effects in reducing cardiovascular risks and may exert an anti-inflammatory effect by inhibiting the MyD88/NF-κB signaling pathway. This finding provides a new perspective for the prevention and treatment of cardiovascular diseases in high-risk individuals with T2DM-ASCVD.

Objective To explore the relationship between haptoglobin gene polymorphism and disease se-verity and susceptibility in senile vascular dementia patients.Methods A total of 80 patients with senile vas-cular dementia admitted to the hospital from February 2018 to February 2023 were selected as the vascular de-mentia group,and 80 stroke patients with non-vascular dementia admitted to the hospital during the same pe-riod were selected as the control group.The genotype distribution and allele frequency of haptoglobin gene were measured using polymerase chain reaction with sequence-specific primers,and their relationship with the severity and susceptibility of vascular dementia patients was analyzed.Results The proportion of history of hyperlipidemia and diabetes mellitus and the levels of total cholesterol and triglyceride in vascular dementia group were higher than those in control group,the differences were statistically significant(P＜0.05).The distribution of genotypes was in Hardy-Weinberg equilibrium(P＞0.05).The frequency of haptoglobin 2-2 genotype and haptoglobin 2 allele in vascular dementia group were higher than those in control group,and the differences were statistically significant(P＜0.05).There were significant differences in the scores of mini-mental state examination and hachinski ischaemic score among patients with vascular dementia with different haptoglobin genotypes(P＜0.05).Multivariate Logistic regression analysis showed that the carrier of hapto-globin 2-2 genotype and the carrier of haptoglobin 2 allele were independent risk factors for vascular dementia(P＜0.05).Conclusion Haptoglobin 2-2 genotype and haptoglobin 2 allele distribution frequency are associ-ated with the occurrence of vascular dementia after stroke,and those with high frequency of haptoglobin 2-2 genotype and haptoglobin 2 allele distribution suffer a severe disease,which can provide reference for early i-dentification and assessment of vascular dementia.

Objective:To analyze the epidemiological and clinical characteristics of respiratory syncytial virus (RSV) infection in children in Jiangsu Province from 2014 to 2023.Methods:The acute respiratory infection cases in children aged 0-14 years were selected from outpatient/emergency or inpatient departments in 2 surveillance sentinel hospitals, respectively, in Nanjing, Suzhou and Taizhou of Jiangsu from 1 July 2014 to 31 December 2023, and RSV nucleic acid test was conducted and the intensity of the RSV infection was accessed by WHO influenza epidemiological threshold method, and case information and clinical data were collected. χ2 test was used to compare the differences between groups, and the Bonferroni method was used for pairwise comparisons between groups. Results:In 4 946 cases of acute respiratory infections, the RSV positive rate was 8.21% (406/4 946), and the age M( Q1, Q3) of the cases was 1 (0, 3) years. The RSV positive rate was 10.92% (258/2 362) during 2014-2019 and 6.06% (118/1 948) during 2019-2023, the difference was significant ( χ2=31.74, P<0.001). RSV infection mainly occurred from October to March during 2014-2019, with the incidence peak in December and moderate or higher intensity. The seasonality of RSV infection was not obvious during 2019-2023, with low intensity. The RSV positive rate was highest in children in age group 0- years (17.85%, 151/846), and the positive rate declined gradually with age ( χ2=184.51, P<0.001). The RSV positive rate was higher in inpatient cases (9.84%, 244/2 480) than in outpatient/emergency cases (6.57%, 162/2 466) ( χ2=17.54, P<0.001). In the 155 RSV infection cases with complete clinical data, the clinical symptoms mainly included cough (99.35%, 154/155), fever (55.48%, 86/155), and shortness of breath (45.16%, 70/155). In the cases aged <6 months, the proportion of those with fever was low, but the proportion of those with shortness of breath, transferred to intensive care units, and receiving oxygen therapy were higher (all P<0.05). Children aged <6 months and those with underlying diseases were more likely to have severe RSV infection (all P<0.05). Conclusions:RSV infection in children in Jiangsu Province showed seasonal prevalence in winter from 2014 to 2019. Since 2020, the seasonal characteristics of the epidemic have changed, the epidemic period has been dispersed and the epidemic intensity has decreased. Infants <1 year old were at high risk for RSV infection, and those <6 months old and with underlying diseases might have severe infection.

Objective:To establish an early clinical prediction model for patients with chronic liver disease who are coinfected with hepatitis E virus (HEV), and quickly evaluate the probability of severe hepatitis in patients.Methods:A retrospective analysis was conducted on 87 patients with chronic liver diseases who were hospitalized at the Third Affiliated Hospital of Sun Yat-sen University from May 2018 to September 2023. Clinical features and laboratory indexes were analyszed and patients were classified to severe (TBIL >171 μmol/L with PTA <40%) and non-severe (TBIL <171 μmol/L with PTA >40%) groups. and Independent factors identified using LASSO regression were incorporated into a novel nomogram to identify patients at high risk of severe hepatitis in the early stages. The performance of the nomogram was evaluated using the area under the curve and the mean absolute error of the calibration curve.Results:Significant difference was observed in the serum total bile acid (TBA) level between the severe group [240.00 (183.30, 268.70) umol/L] and the non-severe group [93.40 (20.10, 271.70) μmol/L, U=269.00, P=0.002]. Additionally, the levels of apolipoprotein A1 (APOA1) [0.32 (0.18, 0.48) g/L] and uric acid (UA) [156.15 (117.00, 202.00) μmol/L] were significantly lower in the severe group compared to the non-severe group (APOA1: [0.77 (0.63, 1.06) g/L, U=71.00, P<0.001]; UA: [334.05 (243.70, 401.00) μmol/L, U=83.00, P<0.001]). The researchers developed a nomogram, which incorporated two independent factors (APOA1 and UA) and an additional variable (TBA), exhibiting a strong predictive ability, with an area under the curve (AUC) of 0.963 (95% confidence interval: 0.927-0.998) and a well-fitted calibration curve. Positive and negative predictive values of 94.0% and 88.2% were calculated, and a nomogram score of 129 or greater was considered indicative of a higher likelihood of developing severe illness. Conclusions:This nomogram offers a rapid and accurate means of evaluating the probability of severe illness in patients with chronic liver disease after overlapping infection with HEV, which can accurately and effectively predict the risk of severe illness in patients.

ObjectiveTo observe the effects of Huqi Zhengxiao Formula （槲芪癥消方） on the survival rate and quality of life of patients with stage Ⅲ hepatitis B-associated primary liver cancer （PLC） with syndrome of healthy qi deficiency and toxic stasis accumulation after transcatheter arterial chemoembolisation （TACE） treatment. MethodsOne hundred and twenty-six patients with stage Ⅲ hepatitis B-associated PLC who were identified as syndrome of healthy qi deficiency and toxic stasis accumulation after TACE treatment were selected， and were randomly assigned to 63 cases each of the treatment group and the control group in a ratio of 1∶1 by using the random number table method； the control group was given symptomatic supportive treatments with western internal medicine， and the treatment group was given the addition of Huqi Zhengxiao Formula on the basis of the control group. All patients were treated for a period of 48 weeks， and were followed up at weeks 4， 8， 12， 24， 36， and 48 of the treatment process. The primary effectiveness index was the 1-year survival rate， and the secondary effectiveness index was the Karnofsky score and the traditional Chinese medicine （TCM） syndrome score. Survival analysis was performed using the Kaplan-meier method， and Log-rank test was used to compare the differences between the survival curves of each group. ResultsSix withdrawals in the treatment group and seven withdrawals in the control group， and finally 57 patients in the test group and 56 patients in the control group were included in the statistical analysis. The 1-year survival rate of patients in the treatment group was 56.1% （32/57）， which was higher than that of 33.9% （19/56） in the control group （P = 0.033）. The mean survival time was （275.30±15.50） days in the treatment group， higher than （227.16±17.11） days in the control group （P = 0.039）. Thirty-two patients in the treatment group and 19 patients in the control group completed the Karnofsky score and TCM symptom score at each time point. At weeks 4， 8， 12 and 36， the difference in the Karnofsky score between the two groups was not statistically significant （P＞0.05）； at weeks 24 and 48， the Karnofsky score in the treatment group was higher than that in the control group at the same time point （P＜0.05）； analysis of variance of repeated measurements found that the downward trend of the Karnofsky score in the treatment group was slower than that in the control group （F = 4.47， P = 0.037）. The difference between the TCM symptom scores of the two groups at each follow-up observation point was not statistically significant （P＞0.05）； there was a tendency for the TCM symptom scores of the two groups to increase， but the ANOVA of repeated measurements found that the difference between the two groups was not statistically significant either （F = 0.31， P = 0.58）. Concusion The oral administration of Huqi Zhengxiao Formula can improve the survival rate， prolong the survival time， and improve the quality of life of patients with stage Ⅲ hepatitis B-associated PLC with syndrome of healthy qi deficiency and toxic stasis accumulations after TACE treatment.

Objective To study the protective effect of polydatin on lipopolysaccharide-induced injury of human umbilical vein vascular endothelial cells(HUVECs)through the protein Janus kinase 2(JAK2)/signal transducers and activators of transcription 3(STAT3)signaling pathway.Methods HUVECs were cultured in vitro,and 500 ng/ml LPS induced their injury and set as a model group;based on the model group,endothelial cells were inter-vened with different concentrations(10,20,and 40 μmol/L)of polydatin for 24 h,and set as polydatin low concentration group,polydatin medium concentration group,and polydatin high concentration group,respectively;a control group was set as another group.CCK-8,monocyte-endothelial cell adhesion,scratch and Transwell assays were used to detect cell viability,adhesion,migration and invasive ability;ELISA was used to detect interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)levels in the cell supernatant;Western blot was used to detect the expression of proteins related to the JAK2/STAT3 signaling pathway levels of JAK2/STAT3 signaling pathway relat-ed proteins.Results Compared with the control group,the model group showed decreased cell survival(P＜0.01),increased cell adhesion,migration and invasion(P＜0.001,P＜0.05,P＜0.01),increased levels of IL-6 and TNF-α in the cell supernatant(P＜0.001),and increased levels of phosphorylation of JAK2 and STAT3 pro-teins in the cells(P＜0.05).Compared with the model group,LPS damage to cells was attenuated after polydatin intervention,cell survival was increased in polydatin low-,medium-and high-concentration groups(P＜0.05),cell adhesion,migration,and invasion decreased(P＜0.05,P＜0.05,P＜0.001),IL-6 and TNF-α levels in cell supernatants decreased(P＜0.05),and the levels of cellular JAK2 and STAT3 protein phosphorylation lev-els decreased(P＜0.05).Conclusion Polydatin seems to reduce the inflammatory injury of human umbilical vein endothelial cells induced by LPS,reducing the secretion of inflammatory factors,and inhibiting the ability of cell ad-hesion,migration and invasion,which may be related to the down-regulation of JAK2/STAT3 signal pathway by polydatin.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.