Objective To construct machine learning models that can be used to predict AUC fold change(FC)using a database of existing pharmacokinetic(PK)and drug-drug interaction(DDI)information,which can be used to explore the possibility of predicting existing drug interactions and to provide certain rational recommendations for clinical drug use.Methods PK data of DDIs and AUC fold change data were extracted from FDA-approved drug labels.Peptide and pharmacodynamic(PD)information related to drug interactions were retrieved through DrugBank,and PPDT identification of relevant peptide IDs was performed using Protein Resource(UniProt),and a matrix normalization code was used to generate multidimensional vector data that were easy to analysis.The effect of PPDT on the AUC,and the resulting multiplicity change was used as the dependent variable for machine learning model construction.The model with the smallest root mean square error(RMES)value was used for model construction to train a bagged decision tree(Bagged)prediction model.The models were tested using the trained models for some of the drug tests.The models were evaluated by reviewing the available literature findings on detection of drug interaction pairs and analyzing and comparing the predicted values.Results A total of 16 pairs of model drug pairs were tested for the effects of 16 drugs on tacrolimus,and it was found that the accuracy of the prediction of the presence or absence of drug interactions was 81.25％;the prediction results were classified according to the FDA standard classification of the strong and weak for the strength of drug interactions,and the results showed that the prediction of the strength of drug interactions,with a large deviation from the larger prediction was less.Conclusion The evaluation of the model to predict the presence or absence of drug interactions was general;however,after classifying the strengths and weaknesses of drug interactions,the prediction of drug interactions was better,and the prediction results indicated that the model prediction performance has a certain reference value for potential DDI assessment before clinical trials.

Objective:This study aims to explore the synergistic effects of DIP and other medical insurance supply-side policies.Method:City A that has piloted DIP reform was set as the treatment group,and City B without reform was set as the control group.A total of 1 120 public medical institution samples from 2019 to 2022 were collected.The total medical expenses during hospitalization and some structural expenses were analyzed using DID method.Result:DIP had a significant inhibitory effect on the medical expenses,and the expenses of checkups and examinations during hospitalization in city A,but had no impact on the drug and the material expenses during hospitalization.Conclusion:DIP played a significant cost control role and effectively controlled the total medical expenses during hospitalization.The synergistic effects of price adjustment of medical services policy and national centralized drug/material procurement policy on cost control were insufficient.DIP synergized with other supply-side policies to promote rational medical cost structure.It is suggested that medical insurance departments should focus on the synergistic effects of medical insurance supply-side policies to jointly improve the efficiency of medical insurance fund utilization.

Purpose To explore the value of contrast-enhanced ultrasound(CEUS)in the differential diagnosis of gallbladder polypoid lesions(GPLs)(diameter≥10 mm).Materials and Methods A prospective enrollment of 229 patients with GPLs who underwent cholecystectomy in 17 hospitals from December 1 2021 to June 30 2024 was conducted to analyze the relationship between general data,conventional ultrasound,CEUS characteristics and the nature of GPLs.Multivariate Logistic regression was employed to identify independent risk factors for neoplastic polyps,the differential diagnostic value of different indicators was compared.Results Among 229 patients with GPLs,there were 108 cases of cholesterol polyps,102 cases of adenoma and 19 cases of gallbladder cancer.Age(Z=-4.476,P<0.001),polyp number(χ2=15.561,P<0.001),diameter(Z=-8.149,P<0.001),echogenicity(χ2=9.241,P=0.010),vascularity(χ2=23.107,P<0.001),enhancement intensity(χ2=47.610,P<0.001),enhancement pattern(χ2=6.468,P=0.011),vascular type(χ2=84.470,P<0.001),integrity of gallbladder wall(χ2=7.662,P=0.006)and stalk width(Z=-9.831,P<0.001)between cholesterol polyps and neoplastic polyps were statistically significant.Age,location,diameter,echogenicity,enhancement pattern,vascular type and stalk width between adenoma and gallbladder cancer were statistically significant(Z=-4.333,-3.902,-5.042,all P<0.05).Multivariate Logistic regression analysis showed that hyper-enhancement,branched vascular type and stalk width were independent risk factors for neoplastic polyps(OR=4.563,5.770,3.075,all P<0.001).The combination of independent risk factors was better than single factor and diameter in the differential diagnosis of cholesterol polyps and neoplastic polyps(all P<0.01).Conclusion CEUS can effectively identify the nature of GPLs and provide a valuable imaging reference for the selection of treatment methods.

Humans ; Pyriform Sinus/surgery* ; Thyroid Neoplasms/diagnosis* ; Fistula/surgery* ; Diagnostic Errors ; Pharyngeal Diseases/surgery*

Ultrasonic bubble detection has been widely used in predicting the risk of decompression sickness and evaluating the efficiency and safety of decompression procedures. Currently, the widely used SPENCER scale is conducted by using Doppler ultrasound to monitor the bubble signal in the precordial region of subjects. KM grading system is a computerized system based on Doppler ultrasound. The grading score can be converted into SPENCER bubble grading scale score and the bubble grading is precise and suitable for the motion status. On the basis of the above two methods, the KISMAN integrated severity score, extended SPENCER bubble grading and simplified Doppler bubble grading system were established. They not only coordinated analysis of Doppler ultrasound bubble detection results with other risk factors of decompression disease, but also convenient to use computer for processing detection results. With the in-depth application of Fourier technique and empirical mode decomposition in Doppler audio bubble signal detection, methods such as three-parameter fuzzy analysis and energy operator method are playing an important role in automatic bubble analysis. Optimization of detection technology and improvement of sensitivity and accuracy of automatic analysis are important development directions in the field of decompression bubble Doppler grating technology.

Objective:To investigate the relationship of swallowing experience to frailty and nutrition in old stroke inpatients. Methods:From March to July, 2019, 174 stroke inpatients aged above 60 were investigated with Dysphagia Handicap Index (DHI), FRAIL Scale and Mini Nutritional Assessment Short Form (MNA-SF). The correlation of DHI score to scores of FRAIL Scale and MNA-SF was analyzed with Pearson correaltion analysis. Multiple regression was analyzed using the scores of dimensions and total score of DHI as dependent variables, and the scores of FRAIL Scale and MNA-SF as independent variables. Results:The inpatients aged (76.16±9.908) years. The DHI score was (50.34±28.325), in which the body score was (17.68±10.254), the function score was (20.31±11.085) and the emotion score was (12.36±9.193). The FRAIL Scale score was (3.16±1.301), and the MNA-SF score was (8.95±2.529). The DHI scores positively correlated with the FRAIL Scale score (r = 0.575, P < 0.001) and negatively correlated with the MNA-SF score (r = -0.544, P < 0.001). The scores of FRAIL Scale and MNA-SF explained the 34.4% of variable for body, 38.7% for function, 36.1% for emotion and 42.4% for DHI total score. Conclusion:Improving the frailty and nutrition may reduce the poor swallowing experience for old stroke inpatients.

Objective:To test the reliability and validity of Work-ability Support Scale (WSS) in stroke patients. Methods:WSS was translated into Chinese with the standard translation-retroversion. From December, 2018 to March, 2019, 193 middle-aged and young stroke patients from two community health service centers in Zhengzhou were conveniently selected, and investigated with Chinese WSS by two nurses. The data were analyzed with item analysis, content validity, exploratory factor analysis, internal consistency reliability and inter-rater reliability. Results:The content validity was 0.94 in WSS A and 0.90 in WSS B. Three factors were extracted from 16 items in WSS A, with cumulative variance contribution of 67.747%; while three factors were extracted from 12 items in WSS B, with cumulative variance contribution of 56.056%. Cronbach's α was 0.933 and 0.778 in WSS A and WSS B, respectively. The kappa coefficient was above 0.6 between two raters in every item, except items B8 and B10. Conclusion:Chinese WSS is satisfactory in validity and reliability for using in young and middle-aged stroke patients during their return to work.

OBJECTIVE To map a comprehensive metabolic pathway of herbacetin in rats, specifically, to elucidate the biotransformation of herbacetin in vivo and to simultaneously monitor the pharmacokinetic process of both parent drug and its major metabolites. METHODS liquid chromatography/ion trap mass spectrometry (LC/MSn) and ultra-liquid chromatography coupled with mass spectrometry (UPLC/MS) were combined in the current study for qualitative and quantitative determinations of herbacetin and its metabolites in bile, urine and feces after both oral and intravenous administration of herbacetin to rats. Enzyme kinetic studies on the intestinal and hepatic metabolism of herbacetin were further conducted to elucidate metabolic profiles of herbacetin in rat tissues and organs. Additionally, plasma concentration profiles of herbacetin and its metabolites in rats were obtained to characterize the overall pharmacokinetic behavior of herbacetin. RESULTS It was found that herbacetin was excreted primarily from rat urine in the form of glucuronide-conjugations. Subsequent in vitro enzyme kinetic studies and in vivo pharmacokinetic investigations suggested an extensive hepatic metabolism of herbacetin and the high exposure of herbacetin- glucuronides in systemic circulation. The clearance, half- life and bioavailability of herbacetin in rats were determined as (16.4±1.92)mL·kg-1·min-1, (11.9±2.7)min, and 1.32%, respectively. On basis of these findings, a comprehensive metabolic pathway of herbacetin in rats was composed. In addition, a physiology based pharmacokinetic (PBPK) model was successfully developed with the aid of the GastroPlus to simulate the pharmacokinetic process of herbacetin in rats. Application of the PBPK modeling can provide a useful starting point to understand and extrapolate pharmacokinetic parameters among different species, populations, and disease states. CONCLUSION After oral administration, herbacetin was subjected to colonic degradation and extensive first pass metabolism, with glucuronidation as its dominating in vivo metabolic pathway.

OBJECTIVE To investigate the effect of hypoxia on the pharmacokinetic process of salidrosidein rats and to explore its underlying mechanisms. METHODS The Caco-2 cell monolayerwas exposed to 1% oxygen (O2) concentration for 24 h to build the hypoxiccell model. The transportation mode of salidroside was investigated with the aid of this hypoxia model by detecting the apparent permeability coefficient(Papp). Healthy Sprague Dawley (SD) rats were exposed to 9% O2 for 72 h for the construction of hypoxic rat model. Liver sample was subsequently collected from the hypoxic rats with an aim to identify enzymes responsible for salidroside metabolism. The expression levels of sali?droside-transporting and salidroside-metabolizing enzymes, including Sodium-dependent glucose cotrans?porters (SGLT1), β-glucosidase (GBA3)and sulfotransferase (SULT2A1), were thereafter detected by RT-PCR and Western blot. The metabolic activity of GBA3 and SULT2A1 was monitored by rat liver microsome incubation.In addition, the renal function of rats under hypoxia was assessed by detecting concentrations of blood urea nitrogen and creatinine. RESULTS The AUC and t1/2 values of salidroside in hypoxic rats were more than doubled, while the in vivo clearance was significantly reduced. Mechanistic study demonstrated that the PappA- B/PappB- A eualsto 10.3, indicating the potential active transport of salidrosile. The expression of SGLT1 and GBA3 was significantly decreased, which indicated a reduced metabolism of salidroside under hypoxia. Moreover, rat under hypoxia was found to suffer from renal dysfunction, with an abnormal value of blood urea nitrogen. CONCLUSION Due to the reduced metabolism and the abnormal renal function under hypoxia, the systemic exposure of salidroside in rats was signifi?cantly enhanced.

We explore the association of the mycoplasma infection with genital system tumor.Some index word including prostate cancer,cervical cancer,ovarian cancer and mycoplasma were used in some electronic databases (including PubMed,Web of Science,Chinese biomedical database,wanfang database,CNKI) to search literatures.The R software was used for the meta-analysis.The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the literature.Publication bias was evaluated by funnel figure,and the fail-safe number (Nfs) was calculated to estimate the reliability of the meta-analysis.Result showed that 20 articles were included,the numbers of cases and controls were 2 345 and 2 728 respectively.The pooled OR of Ureaplasma urealyticum(Uu),Mycoplasma hominis(Mh),other mycoplasma,mixture of mycoplasma and the whole mycoplasma was 2.19(95％CI:1.27-3.79),1.74(95％CI:1.28-2.35),1.97(95％CI:1.03-3.77),3.54 (95％CI:1.33-9.41),1.29(95％CI:1.53-2.60),respectively.The fail-safe number of Uu,Mh,other mycoplasma and mixture of mycoplasma was 254,42,31,157 respectively.There are some possibility about the association between the mycoplasma infection and the genital system cancer;maybe the infection would increase the tumorigenesis risk.It is necessary to research further about these associations in different mycoplasmas respectively.