Objective : To explore the mechanism of isorhamnetin (Iso) in the treatment of oral squamous cell carcinoma (OSCC) using network pharmacology and molecular docking methods and to verify it in vitro. Methods : The key targets were obtained by constructing the PPI protein interaction network based on the common intersection targets of Iso-OSCC. At the same time, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the related signaling pathways of the intersection targets. Iso and core targets were also analyzed through molecular docking and visualization. Colony formation assay and Transwell assay were used to identify the effect of Iso on the proliferation and invasion of Cal-27 cells. Western blot was used to analyze the regulatory effects of different concentrations of Iso on estrogen receptor-1 (ESR1), phosphoinositide-3-kinase regulatory subunit-1 (PIK3R1), Src tyrosine kinase (SRC), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway proteins. Results: A total of 269 potential intersection targets of Iso-regulated OSCC were obtained. According to the degree obtained by topological analysis, PIK3R1, AKT1, SRC, ESR1, and other core targets were screened out. KEGG analysis showed that 165 signaling pathways were enriched in the intersection targets of Iso-OSCC, among which the PI3K/AKT signaling pathway played an important role in the treatment of OSCC with Iso. Molecular docking results showed that the absolute value of binding energy between target proteins PIK3R1, AKT1, SRC, ESR1, and Iso was high. After Cal-27 cells were treated with Iso, the number of cell colony formations, the number of transmembrane cells, and the expression of PIK3R1, ESR1, SRC, p-PI3K, and p-AKT were negatively correlated with the increase in Iso concentration (P < 0.05). Conclusion Iso can inhibit PI3K/AKT signal transduction and influence the expression of PIK3R1, AKT1, SRC, and ESR1 proteins, thereby inhibiting the occurrence and development of OSCC.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

Objective To assess the effects of temperature and rainfall on the incidence of cardiovascular and cerebrovascular diseases (CVD) in Guiyang. Methods Using daily CVD incidence data and temperature and rainfall data in Guiyang City from September 2021 to August 2022, a distributed lag non-linear model was used to explore the nonlinear relationship between meteorological and environmental factors and CVD incidence. Results The risk of CVD was higher under cold (average, minimum, and maximum temperatures <2.1 ℃, 1.6 ℃, and 4.2 ℃, respectively) and hot (maximum temperature>32.5 ℃) effects, and the cumulative lag effect reached its maximum at 10 and 17 days, respectively. The risk of CVD increased sharply when there was a small diurnal temperature (<6.9 ℃), sudden drop in temperature (over 6.1 ℃), and heating (over 2.4 ℃ in 24 hours). The incidence risk of CVD was high when the daily rainfall exceeded 21.5 mm and the continuous rainy days exceed 5.7 days. The risk in rainstorm was 0.81 higher than that in heavy rain. Continuous absence of rain helped to prevent CVD patients from developing symptoms. Conclusion Meteorological environments such as hot and cold weather, dramatic change in temperature, significant rainfall and continuous rainfall have an impact on the incidence of CVD. It is necessary to consider the changes of the meteorological environment during the prevention and control of CVD.

With the development of information technology, the massive growth of pharmaceutical electronic data and the significant increase in the reports of drug adverse event reports have brought great challenges to pharmacovigilance research. Data mining techniques can automatically extract the risk signals of adverse drug reaction from real-world data. Therefore, efficient data mining of massive adverse event reporting is a necessary measure to realize the automatic detection of adverse drug reactions. By introducing the current major large-scale adverse drug event reporting databases and related data mining methods, this study reviews the application and limitations of adverse drug reaction data mining technology in pharmacovigilance, which provides reference for pharmacovigilance-related institutions and researchers.

Objective:To investigatethe heterogeneity of career growth recognition amongphysicians at the stage of standardized training and the growth characteristics of clinical physicians in the early stage, and to provide a reference for improving the quality of standardized training.Methods:The trainees who received standardized residency trainingwere randomly selected from three grade A tertiary hospitals in Chongqing, China. Mplus7.4 was used for latent profile analysis to explain the relationship between explicit continuous indicators, and the subtypes of career growth recognition were analyzed.Results:Career growth recognition at the stage of standardized training was classifiedinto three subtypes of all-round growth recognition, high resource and expectation recognition, and unclassified growth recognition, among which the subtype of unclassified growth recognition accounted for the highest percentage of 40.27% (207 trainees).Conclusions:Physicians at the stage of standardized training show obvious uncertainty aboutcareer growth recognition, and it is necessary to strengthen the education on career growth recognition during standardized training and design a development pathway based on the characteristics of career growth recognition.

Objective:To investigate the relationship between plasma fluoride content, daily calcium intake and blood cell parameters in children and adolescents.Methods:This study was based on the National Health and Nutrition Examination Survey (NHANES) database of the United States from 2013 to 2016, with 3 684 children and adolescents aged 6 - 19 as the research subjects. Information on plasma fluoride content, daily calcium intake and blood cell parameters from the database were collected. Non-linear relationships between plasma fluoride content, daily calcium intake and blood cell parameters were analyzed using restricted cubic splines. If there was a non-linear relationship, the optimal inflection point was calculated using threshold/saturation effect analysis method. Subsequently, multiple linear regression models were used to analyze the associations among the three, and the modification effect of daily calcium intake (binary classification, stratified by median daily calcium intake) on the association between plasma fluoride content and blood cell parameters was analyzed.Results:There was no non-linear relationship between plasma fluoride content and white blood cell count, hemoglobin content and platelet count ( Pnon-linear > 0.05), but there was a non-linear relationship between plasma fluoride content and erythrocyte count and hematocrit ( Pnon-linear < 0.001). After adjusting for confounding factors, the optimal inflection points of the effects of plasma fluoride content on erythrocyte count and hematocrit were 0.54 and 0.31 μmol/L, respectively. There was no non-linear relationship between daily calcium intake and blood cell parameters ( Pnon-linear > 0.05). After adjusting for confounding factors, for every 1 μmol/L increase in plasma fluoride content, the white blood cell count increased by 0.49 × 10 9/L ( P = 0.009). There was a saturation effect in the association between plasma fluoride content, erythrocyte count and hematocrit: when plasma fluoride content was < 0.54 μmol/L, the erythrocyte count decreased by 0.46 × 10 12/L for every 1 μmol/L increase ( P < 0.001). When plasma fluoride content was < 0.31 μmol/L, the hematocrit decreased by 6.29% for every 1 μmol/L increase ( P = 0.006). The above associations were not statistically significant when plasma fluoride content was higher than the optimal inflection points ( P > 0.05). After stratification according to the median daily calcium intake, in the low-calcium group (daily calcium intake < 0.87 g), for every 1 μmol/L increase in plasma fluoride content, the white blood cell count increased by 0.77 × 10 9/L ( P = 0.001). When plasma fluoride content was < 0.54 μmol/L, the erythrocyte count decreased by 0.41 × 10 12/L for every 1 μmol/L increase ( P = 0.002). When plasma fluoride content was ≥0.54 μmol/L, erythrocyte count decreased by 0.47 × 10 12/L for every 1 μmol/L increase ( P < 0.001). When the plasma fluoride content was < 0.31 μmol/L, the hematocrit decreased by 8.29% for every 1 μmol/L increase ( P = 0.011). The above associations were not statistically significant in the high-calcium group (daily calcium intake ≥0.87 g, P > 0.05). There was an interaction of daily calcium intake and plasma fluoride content on platelet count ( Pinteraction = 0.070), as demonstrated by an increase in platelet count of 12.68 × 10 9/L ( P = 0.013) in the low-calcium group and a decrease in platelet count of 9.05 × 10 9/L ( P = 0.035) in the high-calcium group for every 1 μmol/L increase in plasma fluoride content. Conclusions:The blood cell parameters of children and adolescents are closely related to plasma fluoride content, but not directly related to daily calcium intake. However, the correlation between plasma fluoride content and blood cell parameters varies among different calcium intake populations, and daily calcium intake can modify the association between plasma fluoride content and platelet count.

Objective:To study the relationship between adult fluoride exposure and grip strength in rural areas of China with fluorosis, as well as the roles of basal metabolic rate (BMR) and body fat percentage (BFP) in the association between fluoride exposure and grip strength.Methods:From April to May 2017, a cluster sampling method was used to conduct a questionnaire survey, physical examination, and biological sample collection on residents aged 18 - 60 in Tongxu County, Kaifeng City, Henan Province (epidemic areas of drinking-water-borne fluorosis). A total of 1 168 subjects were included in the study, including 427 males and 741 females. The fluoride ion selective electrode method and the picric acid method were used to determine the concentrations of urine fluoride and urine creatinine, and the adjusted urine fluoride concentration (CUF) was calculated. BMR and BFP were measured by a bioelectrical impendence method, and the grip strength was measured by a Jamar grip dynamometer. The relationship between CUF, BMR, BFP and grip strength were analyzed using a generalized linear model regression. The mediation effect model was used to assess the mediating effect of BMR and BFP on the association between CUF and grip strength.Results:Female grip strength decreased by 0.28 kg ( P = 0.043) for every 1.00 mg/L increment in CUF. No similar association was found between the two in males ( P = 0.744). Regardless of gender stratification, BMR was positively correlated with grip strength ( P < 0.001). For every 1.00% increase in BFP, female grip strength decreased by 0.18 kg ( P = 0.043). The mediation effect model analysis results showed that the mediation effect ratios of BMR and BFP in the association between CUF and grip strength in female were 65.1% ( P < 0.001) and 8.4% ( P = 0.111), respectively. Conclusion:Fluoride exposure is associated with changes in female grip strength, and BMR changes play a partial mediating role in the association between fluoride exposure and female grip strength.

Objective To study the application value of pneumonia severity index high-risk score (PSI-HR) in high risk patients and neutrophil-to-lymphocyte ratio (NLR) in the condition evaluation of the pa-tients with respiratory tract infection in ICU.Methods The clinical data of the patients with lower respiratory tract infection hospitalized in the department of intensive care medicine of this hospital from January 2020 to July 2023 were retrospectively analyzed.According to the ICU outcomes,the patients were divided into the im-provement group (n=77) and the poor prognosis group (n=25),and the receiver operating characteristic (ROC) curve was drawn to analyze the evaluation value of PSI-HR score combined with NLR,NLR,PSI-HR score,PSI-HR grade and PSI grade in the prognosis of the patients with lower respiratory tract infection. Results The case fatality rates of the patients with different grades of PSI were 40.00％ (16/40) for the grade 5,18.75％ (6/32) for the grade 4,22.22％ (2/9) for the grade 3 and 4.76％ (1/21) for the grade 2,re-spectively.There was no significant correlation between different PSI grades and case fatality rate (r=0.911,P=0.089).The case fatality rates of different grades of PSI-HR were 75.00％ (3/4) for the grade 6,46.67％ (7/15) for the grade 5,28.57％ (6/21) for the grade 4,17.24％ (5/29) for the grade 3,and 12.12％ (4/33) for the grade 2,respectively,and the PSI-HR grade was positively correlated with the case fatality rate of the patients (r=0.955,P=0.011).The area under the ROC curve (AUC) of predicting the prognosis of the pa-tients with lower respiratory tract infection from great to small was 0.828(95％CI:0.717-0.938,P<0.05) for PSI-HR score combined with NLR,0.754 (95％CI:0.637-0.871,P<0.05) for NLR,0.744 (95％CI:0.636-0.852,P<0.05) for PSI-HR score,and 0.706 (95％CI:0.584-0.829,P<0.05) for PSI-HR grade and 0.695 (AUC=0.695,95％CI:0.582-0.807,P<0.05) for PSI grade.Conclusion The PSI-HR grade has good correlation with the case fatality rate of the patients with lower respiratory tract infection.The effi-ciency of PSI-HR grade combined with NLR for predicting the prognosis in the patients with lower respiratory tract infection in ICU is better than that of single index.

Objective To explore the changes and significane of USP20 and HIF-α expression in breast cancer.Methods Following transfection of shRNA-USP20 lentivirus into breast cancer MDA-MB-231 cells,the gene and protein expression levels of USP20 were detected using fluorescence quantitative PCR and Western Blot.Subsequently,the overexpression of USP20 was observed to determine its effect on HIF-α expression.Similarly,siRNA-USP20 was used to knock down USP20 in breast cancer MDA-MB-231 cells,followed by detection of gene and protein expression levels using fluorescence quantitative PCR and Western Blot.The subsequent changes in HIF-α expression were then examined.Rusults The positive expression rates of USP20 and HIF-α in breast cancer tissues were 69.6%and 46.83%,respectively,while they were negatively expressed in the adjacent normal tissues,with statistically significant differences(P＜0.01).The positive expressions of USP20 and HIF-α were predomi-nantly observed in the cytoplasm of breast cancer tissue,with a smaller amount present in the nucleus.There was a significant positive correlation between USP20 and HIF-α in breast cancer.Following transfection of shRNA-USP20 lentivirus into MDA-MB-231 cells,both the protein and gene expression levels of USP20 significantly increased(P＜0.01).Over-expression of USP20 did not affect HIF-α mRNA levels but led to a significant increase in HIF-α protein expression(P＜0.01).Conversely,siRNA-USP20 interference resulted in a significant decrease in both the protein and gene expression levels of USP20(P＜0.01),without affecting HIF-α mRNA levels;however,it caused a notable reduction in HIF-α protein expression(P＜0.01).Conclusion The expression of USP20 exhib-ited a significant positive correlation with HIF-α in breast cancer.Overexpression of USP20 led to a substantial increase in HIF-α protein expression,while knock-down of the USP20 gene resulted in a significant decrease in HIF-α protein levels.Therefore,it can be inferred that USP20 may exert its influence on the development of breast cancer through modulation of HIF-α expression,thereby providing crucial experimental evidence for clinical treat-ment,prognosis,and further investigations.

OBJECTIVE To investigate the pharmacokinetic characteristics of crossbow microemulsion in rabbit skin.METH-ODS The concentrations of chlorogenic acid,benzoyl new aconitine,periplocin and new aconitine were determined by UPLC.The effects of temperature,perfusion speed and mass concentration on the recovery rate of the probe were investigated by incremental and decrement methods,the changes of multi-component content in the dialysate at different time points after transdermal administration of crossbow microemulsion were determined by UPLC,and DAS 2.0 software was used to process the data.RESULTS The recovery rate of the probe increased with increasing temperature,and the higher the flow rate,the lower the recovery rate.The pharmacokinetic parameters of chlorogenic acid,benzoyl new aconitine,periplocin and new aconitine in microemulsion Cmax were(3.24±0.39)(1.04±0.29)(4.78±2.15)(2.86±0.55)μg·mL-1,respectively,and in AUC0-∞ were(52.42±30.84)(7.70±3.73)(42.23±13.93)(22.68±12.51)h·mg·mL-1,respectively.CONCLUSION A real-time in vivo microdialysis sampling technique was first used and a UPLC detection technique was established to study the skin pharmacokinetics of multi-components of crossbow microe-mulsion after transdermal administration,which provides a reference for the follow-up investigation and application of crossbow microe-mulsion.