OBJECTIVE To know about the perception and current status of drug risk management among pharmacists in Chinese medical institutions， providing insights and recommendations for enhancing the drug risk management system in medical institutions. METHODS A questionnaire survey was conducted across 28 provinces， cities， and autonomous regions； stratified radom sampling was employed to study the population of medical workers and pharmaceutical professionals in medical institutions nationwide. The survey included information on the survey population， the current status of drug risk management implementation in medical institutions， the cognition， definition and process of drug risk management related concepts， and the content and mode of drug risk management work in medical institutions. Finally， suggestions were collected from various medical institutions on the system construction of drug risk management. Descriptive statistical analysis was adopted to summarize the obtained data. RESULTS A total of 446 questionnaires were collected in this survey， including 420 valid questionnaires and 26 invalid questionnaires. The questionnaire collection rate was 100%，and the effective rate was 94.17%. 51.19% of the respondents No.2020YFC2009001）。 based their understanding of drug risk management on Management Measures for Adverse Drug Reaction Reports and Monitoring， while 87.38% recognized the need for drug risk management throughout the drug use process. 63.33% of the participants stated that their medical institutions had dedicated positions related to drug risk management， with the highest proportion （72.17%） was in third-grade class A medical institutions. 66.43% reported implementing risk management across all drug use stages. Suggestions for the development of drug risk management systems in medical institutions by the research participants focused on enhancing guiding documents， clarifying concepts， establishing information-sharing mechanisms. CONCLUSIONS The overall awareness of drug risk management in China’s medical institutions is high， with practices in place across various stages in multiple forms. However， there remains a need to strengthen institutional documents， management regulations， system development， and information-sharing mechanisms to improve collaborative governance， improve drug management levels， and ensure patient safety.

ObjectiveTo explore the impact of exogenous chitosan on the growth and metabolism of Glycyrrhiza uralensis Fisch. (G. uralensis) and to improve the quality of cultivated G. uralensis for both medicine and food and aid in the increase in the content of effective components in G. uralensis.MethodsIn this study, whole G. uralensis plants were treated with exogenous chitosan, and comprehensive analyses of secondary metabolites and proteins were conducted using liquid chromatography with tandem mass spectrometry and isobaric tag for relative and absolute quantitation, respectively. Effects of chitosan induction on endogenous hormones of G. uralensis were analyzed using an enzyme-linked immunosorbent assay. Gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway annotation were conducted to study the effect of chitosan induction on the proteome.ResultsChitosan induction significantly increased the levels of flavonoids in G. uralensis; however, the variation in triterpenoids was not substantial. Biological processes, including photosynthesis, secondary metabolism, and abiotic stress responses, were significantly enriched. Additionally, the photosynthetic pathway, photosynthesis-antenna protein pathway, and plant hormone signal transduction pathway were significantly enriched. In the flavonoid biosynthesis pathway, the upstream-related enzyme phenylalanine ammonia-lyase (PAL) and the downstream-related enzymes chalcone synthase (CHS), polyketide reductase (PKR), chalcone isomerase (CHI), and vestitone reductase (VR) were significantly upregulated.ConclusionsOur findings suggest that chitosan induction may promote the tricarboxylic acid (TCA) cycle, and the TCA cycle enhancement significantly upregulated PAL, CHS, PKR, CHI, and VR, the five key enzymes involved in flavonoid synthesis of G. uralensis, indicating that chitosan induction activated the entire metabolic pathway associated with flavonoids in G. uralensis. Our findings provide a reference for improving the quality of cultivated G. uralensis from the perspective of pharmacodynamic components.

Objective To explore the rule of drug use in treating high-risk cervical human papilloma virus(HPV)infection by using data mining method.Methods Medical records and prescriptions of patients with high-risk HPV infection treated at Wang Jin Outpatient Department of Lishui Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University from January 1,2021 to December 1,2022 were collected.SPSS Modeler 18.0 and SPSS 25.0 were used for drug use frequency,association rules,clustering and other data analysis.Results A total of 100 prescriptions were included,involving a total of 162 Chinese materia medicas,with a total of 1445 times of Chinese materia medicas.The drugs with the highest frequency of use were mainly tonic drugs,antipyretic drugs,regulating vital energy drugs and tranquillizing drugs.Complex network analysis showed that there were close correlation among hedyotis,dried tangerine peel,immature tangerine peel,silktree albizia bark and buffalo horn.Three potential new prescriptions were explored.Conclusion The disease was mostly caused by deficiency in origin and excess in pathological products,and the treatment was to treat both symptoms and root causes,and to attack and supplement,with the treatment of clearing heat and removing toxicity,eliminating dampness,benefiting qi for activating blood circulation and nourishing yin,supplemented by nourishing heart for tranquillization.

Objective To investigate the development of follicles in polycystic ovary syndrome(PCOS)model rats treated with Xinjia Erjia Dihuang Tang and its possible mechanism.Methods Twenty-eight female SD rats with regular estrous cycle were selected and randomly divided into normal control group,model group,Chinese medicine group and Western medicine group,with 7 rats in each group.In addition to the normal control group,the other three groups were continuously given 0.1mg/(kg·d)of letrozole-carboxymethyl cellulose suspension to construct the PCOS rat model.Since the 22nd day,the traditional Chinese medicine group was given 5.268g/(kg·d)of Xinjia Erjia Dihuang Tang,the western medicine group was given 0.286mg/(kg·d)of ethinylestradiol cyproterone tablet,and the normal control group and model group were given 10ml/(kg·d)of distilled water.After 3 weeks,the ovarian coefficients of the rats in all groups were compared,and the morphological changes of the ovarian tissues of the rats in all groups were observed by hematoxylin-eosin staining.The serum hormones of the rats in all groups were detected by enzyme-linked immunosorbent assay,and the ovarian kisspeptin(Kp)and G-protein-coupled receptors(GPR54)protein expression levels were detected by Western blot.Results Compared with the normal control group,the follicles in the ovary of the model group showed more cystic dilatation and atresia,and the number of granular cell layers decreased,the ovarian coefficient of the model group was increased;Serum levels of testosterone(T),luteinizing hormone(LH)and Kp were increased in model group;Serum levels of follicle stimulating hormone(FSH)and estradiol(E2)and protein expressions of Kp and GPR54 in ovarian tissue of rats in the model group were significantly decreased(P<0.05).After treatment with Chinese medicine,compared with the model group,the number of follicles in the Chinese medicine group decreased,the layer number of granulosa cells increased,there were nearly mature follicles,and a small amount of corpus luteum existed,serum LH,T and Kp levels were decreased,serum FSH and E2 levels and ovarian Kp and GPR54 protein expressions were significantly increased(P<0.05).Conclusion The development of follicles in PCOS model rats was improved by the intervention of Xinjia Erjia Dihuang Tang.The therapeutic mechanism may be to affect the release of FSH and LH by regulating Kisspeptin/GPR54 system,so as to affect hormone content,adjust ovarian function,and improve follicle development and ovulation ability.

OBJECTIVE To establish a method for concentration determination of caffeine and its three metabolites， theophylline， paraxanthine and theobromine in urine， and apply it in clinical practice. METHODS Using caffeine-13C3-d3 as internal standard （IS）， and the urine samples were protein precipitated with acetonitrile； HPLC-MS/MS method was adopted to determine the concentrations of caffeine and its three metabolites. The determination was performed on Waters ACQUITY UPLC® BEH HILIC column with mobile phase consisting of 60 mmol/L ammonium acetate （A）-acetonitrile （B） （gradient elution） at the flow rate of 0.5 mL/min. The column temperature was set at 38 ℃ ， and the sample size was 2 μL. The electrospray ionization detection was operated in a positive mode by multiple reaction monitoring. The detection ions for quantitative analysis were m/z 195.1→110.0 for caffeine， m/z 181.1→124.0 for theophylline， m/z 181.1→124.0 for paraxanthine， m/z 181.1→138.0 for theobromine， and m/z 198.1→ 140.1 for IS. The above method was used to determine the concentrations of caffeine and its three metabolites in the urine of 19 infants with apnea of prematurity （AOP）. RESULTS The linear ranges of mass concentration of caffeine， theophylline， paraxanthin and theobromine were 0.200-200， 0.050-50.0，0.050 0-50.0， and 0.100-100 μg/mL， respectively. The lower limits of quantification were 0.200， 0.050， 0.050 and 0.100 μg/mL （r＞0.990）， respectively. RSDs of intra-day and intra- day precision were not above 10.37%， and matrix factors were 85.68%-109.90%； extraction recoveries were 93.53%-109.40% （RSD≤15%）， and RSDs of stability tests were all lower than 15%. The concentrations of caffeine and its three metabolites in the urine of 19 cases were （27.346±7.951）， （0.351±0.223）， （0.428±0.395） and （0.472±0.374） μg/mL， respectively. CONCLUSIONS The established HPLC-MS/MS method is simple， sensitive and can be used for the determination of caffeine and its three metabolites in urine samples of AOP.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC_50s for BD and BC were 11.63 and 11.71 μmol·L^-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
Humans ; Lung Neoplasms/metabolism* ; STAT3 Transcription Factor/metabolism* ; Antineoplastic Agents/chemistry* ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation

Objective:To establish autoverification rules for coagulation tests in multicenter cooperative units, in order to reduce workload for manual review of suspected results and shorten turnaround time (TAT) of test reports, while ensure the accuracy of results.Methods:A total of 14 394 blood samples were collected from fourteen hospitals during December 2019 to March 2020. These samples included: Rules Establishment Group 11 230 cases, including 1 182 cases for Delta check rules; Rules Validation Group 3 164 cases, including 487cases for Delta check; Clinical Application Trial Group 77 269 cases. Samples were analyzed for coagulation tests using Sysmex CS series automatic coagulation analyzers, and the clinical information, instrument parameters, test results, clinical diagnosis, medication history of anticoagulant and other relative results such as HCT, TG, TBIL, DBIL were summarized; on the basis of historical data, the 2.5 and 97.5 percentile of all data arranged from low to high were initially accumulated; on the basis of clinical suggestions, critical values and specific drug use as well as relative guidelines, autoverification rules and limits were established.The rules were then input into middleware, in which Stage I/Stage II validation was done. Positive coincidence, negative coincidence, false negative, false positive, autoverification pass rate, passing accuracy (coincidence of autoverification and manual verification) were calculated. Autoverification rules underwent trial application in coagulation results reports.Results:(1) The autoverification algorisms involve 33 rules regarding PT/INR, APTT, FBG, D-dimer, FDP,Delta check, reaction curve and sample abnormalities; (2)Autoverification Establishment Group showed autoverification pass rate was 68.42% (7 684/11 230), the false negative rate was 0%(0/11230), coincidence of autoverification and manual verification was 98.51%(11 063/11 230), in which positive coincidence and negative coincidence were respectively 30.09% (3 379/11 230) and 68.42%(7 684/11 230); Autoverification Validation Group showed autoverification pass rate was 60.37%(1 910/3 164), the false negative rate was 0%(0/11 230), coincidence of autoverification and manual verification was 97.79%(3 094/3 164), in which positive coincidence and negative coincidence were respectively 37.42%(1 184/3 164) and 60.37%(1 910/3 164); (3) Trialed implementation of these autoverification rules on 77 269 coagulation samples showed that the average TAT shortened by 8.5 min-83.1 min.Conclusions:This study established 33 autoverification rules in coagulation tests. Validation showedthese rules could ensure test quality while shortening TAT and lighten manual workload.

Iodine and fluoride are indispensable elements of human life activities,excessive or insufficient intakes can cause diseases,especially thyroid diseases,the relationship between iodine,fluoride and thyroid diseases has been paid more and more attention.The water iodine and fluoride are an important source of human intakes,so researching the influence of water iodine and fluoride on thyroid diseases is of great significance for guiding the population to maintain normal thyroid morphology and function.

Objective To explore the relationship between iodine and fluoride content in drinking water and the incidence of adult thyroid nodules in Cangzhou,Hebei.Methods According to the previous reports on iodine and fluoride levels in drinking water in Cangzhou,from November 2016 to January 2017,Cangzhou was divided into high iodine,low iodine,normal iodine and fluorine,low iodine and high fluorine,high iodine and high fluorine areas,and according to the different contents of iodine and fluorine in drinking water,high iodine and high fluorine area was further divided into high iodine and high fluorine 1 (iodine:743.30 μg/L,fluorine:4.27 mg/L),2 (iodine:119.31μg/L,fluorine:4.67 mg/L) and 3 (iodine:105.30 μg/L,fluorine:1.64 mg/L) subareas.Subjects who lived for 20 or more years and aged 30 or older,without serious disease and not taken iodized salt were selected.Palpation was used to examine the size,texture,mass,tenderness and mobility of the thyroid gland.The boundary,internal echo,blood flow and quantity of nodules were observed and recorded by color Doppler.Results The prevalence difference of thyroid nodules [36.8％ (629/1 710),32.8％ (636/1 938),25.1％ (427/1 700)] in high iodine,low iodine and normal iodine and fluorine areas was statistically significant (x2 =55.597,P ＜ 0.05).The prevalences of thyroid nodules in both high iodine and low iodine areas were higher than that of normal iodine and fluorine area (P＜ 0.016 7).The prevalence difference of thyroid nodules [43.3％ (749/1 730),39.8％ (712/1 790),34.9％ (623/1 785)] in high iodine and high fluorine 1,2 and 3 subareas was statistically significant(x2 =26.220,P ＜ 0.05).Compared with low iodine area,the prevalence of thyroid nodules [41.2％ (735/1 785)] in low iodine and high fluorine area was increased (x2 =6.288,P ＜ 0.05).Conclusions Both high iodine and low iodine can induce thyroid nodules.In water source areas with high iodine content,both high iodine and high fluorine are the factors inducing thyroid nodules.The prevalence of thyroid nodules in low iodine and high fluorine area is significantly higher than that of low iodine area.

BACKGROUND/AIMS: Microvascular invasion (MVI) is an established risk factor for hepatocellular carcinoma (HCC). However, prediction models that specifically focus on the individual prognoses of HCC patients with MVI is lacking. METHODS: A total of 385 HCC patients with MVI were randomly assigned to training and validation cohorts in a 2:1 ratio. The outcomes were disease-free survival (DFS) and overall survival (OS). Prognostic nomograms were established based on the results of multivariate analyses. The concordance index (C-index), calibration plots and Kaplan-Meier curves were employed to evaluate the accuracy, calibration and discriminatory ability of the models. RESULTS: The independent risk factors for both DFS and OS included age, tumor size, tumor number, the presence of gross vascular invasion, and the presence of Glisson's capsule invasion. The platelet-to-lymphocyte ratio was another risk factor for OS. On the basis of these predictors, two nomograms for DFS and OS were constructed. The C-index values of the nomograms for DFS and OS were 0.712 (95% confidence interval [CI], 0.679 to 0.745; p<0.001) and 0.698 (95% CI, 0.657 to 0.739; p<0.001), respectively, in the training cohort and 0.704 (95% CI, 0.650 to 0.708; p<0.001) and 0.673 (95% CI, 0.607 to 0.739; p<0.001), respectively, in the validation cohort. The calibration curves showed optimal agreement between the predicted and observed survival rates. The Kaplan-Meier curves suggested that these two nomograms had satisfactory discriminatory abilities. CONCLUSIONS: These novel predictive models have satisfactory accuracy and discriminatory abilities in predicting the prognosis of HCC patients with MVI after hepatectomy.
Calibration ; Carcinoma, Hepatocellular ; Cohort Studies ; Disease-Free Survival ; Hepatectomy ; Humans ; Multivariate Analysis ; Nomograms ; Prognosis ; Risk Factors ; Survival Rate