Objective To explore the correlation between the incidence of foodborne diseases and meteorological factors in Jinan, and to provide targeted measures for the prevention and control of foodborne diseases. Methods Data from the reporting systems of two sentinel hospitals for active surveillance of foodborne diseases from 2013 to 2021 in Jinan were collected. The meteorological data in the same period in Jinan were also collected. The generalized additive model was used to explore the nonlinear relationship between meteorological factors and the incidence of foodborne diseases, and threshold function analysis was use to perform subsection regression. Results The incidence of foodborne diseases was positively correlated with daily average temperature (r_s=0.23), relative humidity (r_s=0.05), and daily average wind speed (r_s=0.01), and negatively correlated with daily average air pressure (r_s=-0.19). Based on the GAM results and segmented regression analysis of meteorological factors, it was found that when the daily average temperature was below or above the threshold of 24.63°C, for every 1°C increase in daily average temperature, the incidence of foodborne diseases correspondingly increased by 0.04% and 0.18%. When the daily average wind speed was above the threshold of 2.26 m/s, the incidence of foodborne diseases decreased by 0.36% for every 1 m/s increase in the daily average wind speed. Conclusion Nine years of observation and data analysis have shown that meteorological factors such as daily average temperature, relative humidity, air pressure, and wind speed are related to the incidence of foodborne diseases. These findings suggest that meteorological factors may be important factors leading to foodborne diseases, which provides an important scientific basis for formulating effective prevention and control measures.

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG _FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG _EXP (the mean absolute deviations | Δ G FEP - Δ G EXP |  < 2 kcal/mol) than those ΔG _MM-PBSA or ΔG _MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC₅₀ of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.

OBJECTIVE：To prepare Azelnidipine enteric solid dispersion and evaluate its quality. METHODS ：Azelnidipine enteric solid dispersion was prepared by solvent method. Taking cumulative dissolution rate as the index ，single factor test was used to optimize carrier material type and its ratio. The quality of the product was evaluated by DSC ，XRD and FTIR ，and its stability was investigated. RESULTS ：After azelnidipine and carrier material of Eudragit L 100-55 acrylic resin were prepared to enteric solid dispersion at a ratio of 1∶5（m/m），its dissolution rate was significantly improved. DSC ，XRD and FTIR method had all verified the crystal form of azelnidipine changed and it existed in amorphous form. The results of stability test showed that Azelnidipine enteric solid dispersion was stable under high temperature （60 ℃），high humidity （75％）and strong light [ （4 500±500）lx] for 10 days. CONCLUSIONS ：Azelnidipine enteric solid dispersion by solvent method with Eudragit L 100-55 acrylic resin as carrier can eliminate the influence of crystal form ，improve dissolution and has good stability.

Objective: To investigate the current situation and influence factors of perceived professional benefits among nurses working in day-care unit. Methods: Convenience sampling method was adopted, totally 245 nurses working in day-care unit were investigated by nurses' perceived professional benefit questionnaire, psychological capital questionnaire, psychological sub-health questionnaire and a self-designed demographic questionnaire. The data were collected and analyzed statistically. Results: The scores of perceived professional benefit among nurses working in day-care unit were 117.96±14.06. Multiple regression analysis shows that working years, scores of psychological capital questionnaire and psychological sub-health questionnaire were positive factors to perceived professional benefit; while the education level was negative predictors to perceived professional benefit. The regression equation was: the scores of perceived professional benefit among nurses = 70.582-4.882 x the education level + 2.520 x working years+ 0.329 x scores of psychological capital questionnaire + 0.250 x psychological sub-health questionnaire. Conclusions It showed higher level of perceived professional benefit as tested in previous study. Managers can pay more attention to nurses with less working years and higher degree of education, and improve the level of psychological capital and mental health, so as to improve the level of perceived professional benefit.

OBJECTIVE： To establish a quantitative analysis of multi-components by singer marker （QAMS） for determining the contents of diosgenin， 5-hydroxymethylfurfural， vanillic acid， rutin， quercetin， kaempferol in Polygonati Rhizoma and its decoction piece. METHODS： HPLC external standard method was used to determine the contents of 6 components in Polygonati Rhizoma and its decoction piece simultaneously [the separation was carried out on Diamonsil-C18 column with mobile phase consisted of acetonitrile-water （gradient elution）； the detection wavelengths of 5-hydroxymethylfurfural， vanillic acid， rutin， quercetin and kaempferol were set at 254 nm（0-60 min）； the detection wavelength of diosgenin was set at 202 nm （60-75 min） at the flow rate of 1.0 mL/min. The column temperature was 30 ℃]. Using vanillic acid as internal standard， relative correction factors （RCFs） of aother 5 components were calculated and to investigate durability. Relative retention method was used to accurately locate the chromatographic peaks of the components to be determined， and then the contents of the aother 5 components in Polygonati Rhizoma were calculated according to RCFs， and the results were compared with those determined by external standard method. The method was validated by Polygonati Rhizoma decoction piece. The contents of 6 components were determined by QAMS method and external standard method respectively， and then the differences of content determination were compared between 2 methods. RESULTS： The methodology investigation results of HPLC method were in line with related requirements. Within the linear range， the RCFs of diosgenin， 5-hydroxymethylfurfural， rutin， quercetin， kaempferol were 0.195， 0.025， 0.263， 0.345 and 0.075， respectively. Under different experiment conditions， RCFs showed good reproducibility； there was no statistical significance of 6 components in Polygonati Rhizoma and its decoction piece determined by external standard method and QAMS method （P＞0.05）. CONCLUSIONS： Established QAMS method is suitable for simultaneous determination of 6 components in Polygonati Rhizoma and its decoction piece.

PURPOSE: The prevalence of PIK3CA in Chinese breast cancer patients may be underestimated. Therefore, we investigated the distribution of somatic PIK3CA/AKT1 mutations in Chinese breast cancer patients and explored their roles in tumor phenotypes and disease prognosis. MATERIALS AND METHODS: Tumors from 507 breast cancer patients were prospectively collected from the West China Hospital between 2008 and 2013. Whole exons of AKT1 and PIK3CA were detected in fresh-frozen tumors using next-generation sequencing, and correlations between PIK3CA/AKT1 mutations and clinicopathological features were analyzed. RESULTS: The AKT1 mutation was found in 3.6% (18/507) of patients. Tumors from patients that carried the AKT1 mutation were estrogen receptor (ER)+/progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2)‒ and were more likely to have high expression levels of Ki67. The prevalence of the PIK3CA mutation was 46.5% (236/507), and 35 patients carried two or three variants of the PIK3CA gene. PIK3CA mutations were associated with ER+/PR+/HER2‒ status. The prognosis of patients with one mutation in PIK3CA (or PIK3CA/AKT1) was not significantly different than that of patients with wild-type PIK3CA (or PIK3CA/AKT1), while patients with two or three variants in PIK3CA (or PIK3CA/AKT1) exhibited poorer outcomes in the entire group and in all three subgroups (ER+, HER2‒, Ki67 high), particularly with respect to overall survival. CONCLUSION: A high frequency of somatic PIK3CA mutations was detected in Chinese breast cancer patients. In addition to the mutation frequency, the tumor mutational burden of the PIK3CA and AKT1 genes should also be of concern, as they may be associated with poor prognosis.
Asian Continental Ancestry Group* ; Breast Neoplasms* ; Breast* ; China ; Estrogens ; Exons ; Humans ; Mutation Rate ; Phenotype ; Prevalence* ; Prognosis ; Prospective Studies ; Receptor, Epidermal Growth Factor

Objective To explore the effects of problem-based bedside nursing teaching in clinical teaching. Methods Totally 247 college nursing students were recruited in the study from July 2016 to June 2017. The 118 students were in the experimental group which implemented problem-based bedside nursing teaching,while 129 students were in the control group which implemented traditional teaching.The teaching effects of two groups at the end of practice was compared with mini-CEX. Results The clinical nursing comprehensive ability of the experimental group was 6.42±1.45,the control group was 5.25±1.35,the difference was statistically significant(t=15.73,P=0.000).The clinical teaching effect of the experimental group was better than that of control group,41.53%(49/118)and 51.69%(61/118)met the requirements and reached excellence, and 62.79%(81/129)and 19.38%(25/129)in the control group.The difference was statistically significant (Z=-5.35, P=0.000). Conclusions The model of bedside teaching based on problem can significantly improve nursing students'clinical nursing comprehensive ability and improve clinical teaching effect.

Improvement of pharmaceutical qualification examination system is important for systematic and professional development of pharmaceutical industry.Korea has set up the pharmaceutical qualification examination system including pharmacy education eligibility test and pharmacist state examination.Pharmacy education eligibility test aims to select talents to get 2+4 years' pharmacy higher education and the competitiveness showed a trend of increase implemented since 2010.The candidates always major in engineering/natural/agriculture,chemistry,biology,humanistic society and ect,during preparatory course.While average pass rate of'pharmacist state examination was only 73.7％,which act as the passport to becoming a pharmacist of Korea,showed high difficulty compared to physicians and nurses.The pharmaceutical professional talents selection system in Korea was established through the difficult and sustainable pharmacy qualification examination system,and achieved the systematic,professional development of pharmaceutical industry,which can be used for reference for China.

According to the characteristics of postgraduates of clinical medicine and features of radiology and based on traditional teaching, picture archiving and communicating system (PACS), tutorial system, lecture and modernized tests with the help of problem-based learning (PBL) were ap-plied so that the effect of students' rotation internship was improved.