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 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 demonstrate the polymorphism of α chain of bovine major histocompatibility complex(BoLA)classⅠmolecule and domain binding constant chain(Ii).Methods:Total 75 BoLA Iα genes were obtained from three Huaibei cattle and analyzed by molecular biology software;the genes of typical BoLA Iα domains and Ii were cloned,and then inserted into prokaryotic expression plasmid.After induced protein expression;the domains of BoLA Ⅰα chain binding to Ii were detected by pull-down meth-od and Western blot.The recombinant eukaryotic expression plasmids were constructed and the co-localization of BoLA Iα segments with Ii was observed by laser confocal microscopy.Results:Firstly,it was found that there were at least 5 kinds of BoLA Iα in the cloned gene sequence,which were highly polymorphic and they were mainly distributed in the antigen peptide binding region(PBR)of BoLA Ⅰ(α1α2)and cytoplasmic region.Secondly,the prokaryotic recombinant plasmids containing BoLA Ⅰα1α2α3,BoLA Ⅰα1α2 or BoLA Ⅰα 3 were constructed,then they were respectively induced to express and purified,in which,the BoLA Ⅰα1α2α3 and BoLA Ⅰα1α2 had the activity of binding to Ii.Finally,in 293T cells BoLA Ⅰα1α 2α3 or BoLA Ⅰα1α2 was found that could co-localize with Ii,while a single BoLA Ⅰα3 could not.Conclusion:BoLA Ⅰα gene is highly polymorphic.BoLA Ⅰα1α2 is a func-tional fragment that binds to Ii and co-locates intracellular.

Objective:To compare Al 18F-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04 PET/CT with 18F-FDG PET/CT in the evaluation of patients with initial gastric cancer. Methods:Twenty patients (13 males, 7 females, age: 27-77 years) with histologically proven gastric cancer were recruited prospectively between March 2021 and July 2022 in the First Affiliated Hospital of Zhengzhou University. Each patient underwent both 18F-FDG and Al 18F-NOTA-FAPI-04 PET/CT within one week. SUV max, tumor background ratio (TBR) and positive detection rate of the two methods were compared (Wilcoxon signed rank sum test, McNemar χ2 test). Results:Al 18F-NOTA-FAPI-04 showed higher SUV max and TBR than those of 18F-FDG in primary tumors (10.2(8.0, 13.7) vs 5.2(3.3, 7.7), z=-3.47, P=0.001; 7.6(5.6, 10.3) vs 2.4(1.8, 3.0), z=-3.85, P<0.001). For the detection of primary gastric cancer, the positive detection rate of Al 18F-NOTA-FAPI-04 PET/CT showed the trend of being higher than that of 18F-FDG PET/CT (95%(19/20) and 75%(15/20); χ2=2.25, P=0.125). For assessing lymph node metastasis, the detection rate of Al 18F-NOTA-FAPI-04 PET/CT was higher than that of 18F-FDG PET/CT (78.9%(101/128) vs 64.8%(83/128); χ2=13.47, P<0.001). The SUV max and TBR of Al 18F-NOTA-FAPI-04 in lymph node were higher than those of 18F-FDG (5.3(3.5, 9.2) vs 2.8(1.8, 4.7), z=-7.31, P<0.001; 4.6(2.6, 6.5) vs 1.7(1.0, 3.0), z=-8.44, P<0.001). For the detection of peritoneal carcinomatosis, Al 18F-NOTA-FAPI-04 PET/CT showed higher peritoneal cancer index (PCI), SUV max, and TBR compared to 18F-FDG PET/CT (PCI: 12.0(3.0, 29.8) vs 5.5(0.5, 17.5), z=-2.22, P=0.026; SUV max: 8.2(4.4, 12.5) vs 2.7(1.9, 4.0); z=-2.52, P=0.012; TBR: 5.1(2.9, 13.3) vs 1.1(0.9, 2.0); z=-2.52, P=0.012). Conclusion:Al 18F-NOTA-FAPI-04 PET/CT outperforms 18F-FDG PET/CT in primary and metastatic lesions of gastric cancer and might be a potential novel modality for imaging patients with gastric cancer.

[Objective]To summarize the clinical experience of Professor CHEN Jian in treating periodic fever syndrome(PFS)in children from"latent fire".[Methods]Through outpatient follow-up study,collection of medical records and review of relevant literature,this paper summarized the etiology,pathogenesis and Professor CHEN's treatment experience of PFS in children from"latent fire",and a case was presented for verification.[Results]Professor CHEN believes that the core pathogenesis of PFS in children is"latent fire".Phlegm,poison and stasis are not only pathological products,but also important pathogenic factors throughout the course of the disease.Depression is the pathological state of the whole course of the disease.In the treatment,the method of supplementing Qi to remove heat or nourishing Yin to clear heat is used and combined with regulating Qi,and the self-prepared prescription is the effective treatment of PFS in children.The main symptom of the case was periodic fever,which was differentiated as Yin deficiency fever.The treatment of nourishing Yin and clearing heat,promoting Qi movement and relieving depression was applied,and good effect was achieved.[Conclusion]Professor CHEN's treatment of PFS in children from"latent fire"is effective,has certain guiding significance,and is worthy of clinical reference.

Objective To understand the timeliness of antiretroviral therapy (ART) in newly reported HIV/AIDS cases in Yichang from 2016 to 2022 and its influencing factors, and to provide a scientific basis for improving the timeliness of ART in Yichang City. Methods HIV/AIDS cases data from January 1, 2016 to December 31, 2022 were collected, and chi-square tests and logistic regression were used to analyze the factors influencing the timeliness of ART. Results A total of 1 126 HIV/AIDS cases were collected, with local reported cases accounting for 83.13%. The male to female ratio was 5.15:1. The median age was 42 years old (28-53 years old). 41.03% of the cases were unmarried. 38.99% of cases had a first-time CD4+T lymphocytes (CD4 cells) count < 200 cells/µL. Cases with timely first CD4 cell test accounted for 67.85%. The overall timely rate of ART from 2016 to 2022 was 57.19%, with a median time from diagnosis to initiation of ART of 20 days. There was no statistically significant difference in the trend of ART timely rate from 2016 to 2022 (P=0.251). Cases with timely first CD4 cell test were more likely to initiate ART in time (OR=3.831, 95% CI:2.454-5.981), while cases reported from other areas (OR=0.497, 95% CI:0.345-0.716) and cases with higher first CD4 cell count levels (OR_≥500=0.473, 95% CI:0.312-0.718) were less likely to initiate ART in time. Conclusion The timely rate of antiviral treatment in Yichang City needs to be further improved. High attention should be paid to cases reported from other places, cases with delayed CD4 cell testing, and cases with high CD4 cell count levels. Treatment mobilization and referral should be done well, and early detection services should be provided in time.

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.

Objective:To investigate the effects of long-term exposure to chrysotile and crocidolite on miRNAs and epithelial mesenchymal transformation (EMT) -related gene expression in human pleural mesothelial cells.Methods:In November 2020, fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of EMT-related genes in human pleural mesothelioma cells (NCl-H2052 cells, NCl-H2452 cells) and human normal mesothelial cells (Met-5A cells). MiRNAs with abnormal expression in human pleural mesothelioma cells were screened out from the previous miRNA chip data of research group, and target genes of differentially expressed miRNAs were predicted using miRWalk database (http: //mirwalk.umm.uni-heidelberg.de). RT-qPCR was used to verify the abnormal expression of EMT-related miRNAs in cell lines. Met-5A cells were treated with 5μg/cm 2 chrysotile and crocidolite respectively for 48 h a time, once a week and a total of 10 times. Chrysotile group, crocidolite group and control group were set up. And the control group was added with the same volume of PBS. The expression changes of EMT-related genes and abnormal expression miRNAs in each group were detected by RT-qPCR. The differences among the groups were compared by one-way ANOVA, and the differences between the control group and the experimental group were compared by dunnet- t test. Results:Compared with Met-5A cells, the expression levels of Vimentin and Twist genes were increased, and the expression level of E-cadherin genes was decreased in NCl-H2052 cells and NCl-H2452 cells ( P<0.001). Target genes of miRNAs with abnormal expression in miRNA chip were predicted, and the results showed four abnormally expressed miRNAs associated with EMT and verified the expression of these four miRNAs in the cell lines. Compared with Met-5A cells, the expression level of hsa-miR-155-5p was increased in NCl-H2052 cells and NCl-H2452 cells, the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased in NCl-H2052 cells and NCl-H2452 cells ( P<0.001), which was consistent with the results of chip analysis. After exposure of Met-5A cells, it was found that compared with the control group, the expression levels of Vimentin and Twist genes, hsa-miR-155-5p, hsa-miR-34b-5p and hsa-miR-34c-5p in the crocidolite group were increased, while the expression level of E-cadherin gene was decreased ( P<0.05). Compared with the control group, the expression levels of Vimentin, Twist and E-cadherin genes in chrysotile group were increased, while the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased ( P<0.05) . Conclusion:Long-term exposure to chrysotile and crocidolite could cause Met-5A cells to produce miRNAs and EMT-related gene expression changes similar to mesothelioma cells.

Objective To investigate the effect of rehabilitation instruction based on resourceful theory on the execution intention of exercise behaviour in patient with the first-episode stroke.Methods From September 2022 to February 2023,a total of 80 inpatients with first-episode stroke from a general hospital in Anhui Province participated in the study.Patients in Wards Ⅰ and Ⅱ were assigned to an intervention group,while those in Wards Ⅲ and Ⅳ were assigned to a control group,with 40 patients per group.The patients in control group received standard interventions,while those in the intervention group were offered with a rehabilitation instruction based on resourceful theory in addition to the standard interventions.Stroke patient rehabilitation exercise behaviour execution intention questionnaire,resourcefulness scale and modified Barthel were employed for assessments before and after the intervention.Results After the intervention,the intervention group showed significantly higher scores inexecutive intention of exercise behaviour,resourcefulness level and daily living activities compared to those in the control group(all P＜0.01).Conclusion Rehabilitation instruction based on the theory of resourcefulness can effectively increase the executive intention of exercise behaviour in the patients with first-episode stroke,improve the resourcefulness thinking levels and enhance the daily living activity of the patients.