Objective To establish an ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS)method for identifying the active ingredients of Zhizi Houpu decoction,and to predict its material basis and mechanism of anti-insomnia effects using network pharmacology.Methods The chemical components of Zhizi Houpu decoction were identified according to UHPLC-QTOF-MS ion fragmentation rule combined with compound library and literature review.Components with oral bioavailability(OB)≥30％and drug-like properties(DL)≥0.18 were selected to construct the Zhizi Houpu decoction-active ingredients-target network.The STRING database and the Database for Annotation,Visualization,and Integrated Discovery(DAVID)were used to screen key target proteins.Subsequently,enrichment analysis was performed for biological processes,molecular functions,cellular components,and signaling pathways.Results A total of 107 chemical components were identified,including 35 compounds related to insomnia and 11 anti-insomnia targets such as AKT serine/threonine kinase 1,tumor protein 53,and prostaglandin-endoperoxide synthase 2.Gene Ontology functional enrichment analysis indicated that Zhizi Houpo decoction may exert its effects through cellular components such as the presynaptic membrane,dendrite,and plasma membrane,by participating in biological processes like chemical synaptic transmission,G protein signaling pathway,and neuron apoptosis,and by regulating molecular functions such as G protein-coupled serotonin receptor activity.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that its anti-insomnia effects were mainly concentrated in pathways such as neuroactive ligand-receptor interaction,calcium signaling pathway,serotonergic synapse,and cyclic adenosine monophosphate signaling pathway.Conclusion The anti-insomnia effect of Zhizi Houpo decoction is the result of a synergistic action involving multiple components,multiple targets,and multiple pathways.Its material basis and mechanism of action are primarily related to regulating biological processes such as neurotransmitter metabolism,synaptic function,neuronal apoptosis,and inflammatory response.

Objective: To explore the clinical application value of neural network technology,and to screen the clinical early warning indicators of severe hand-foot-mouth disease(HFMD) by constructing a back propagation neural network(BPNN) model. Methods: The clinical data of children with HFMD admitted to the Department of Infectious Diseases and Pediatrics of the First Affiliated Hospital of Xinxiang Medical University from January2019 to January 2023 were collected.The data were divided into 70% training samples and 30 % test samples using SPSS Modeler 18.0.The BPNN model and Logistic model were constructed to compare and evaluate the prediction accuracy and screening effect of the model. Results: The clinical data of 589 children were collected and analyzed,including 324 cases in the mild group and 265 cases in the severe group.The prediction accuracy of the test set(n=178) of BP neural network model and Logistic regression model was 82.02% and 84.83%,respectively.The area under the ROC curve(95% CI) was 0.791(0.749-0.834) and 0.625(0.577-0.674),respectively.Among the predictive variables output by the BPNN model,the top five factors that had the greatest impact on the grouping were highest body temperature,duration of fever,glutamyl transpeptidase,aspartate aminotransferase,and globulin.There were 3 of the top 10 overlaps in the importance of the predictive variables output by the two models,which were the highest body temperature,duration of fever and limb shaking. Conclusion The BPNN model and Logistic regression model perform well in screening and verifying the risk factors of severe hand-foot-mouth disease,but the comprehensive prediction performance of BP neural network model is better.The top five influencing factors of severe HFMD screened by the BPNN model are the highest body temperature,duration of fever,glutamyl transpeptidase,aspartate aminotransferase and globulin.

Objective To investigate the value of transient elastography (FibroScan) and platelet count-to-spleen thickness (PC/ST) ratio in predicting the degree of esophageal and gastric varices (EGV) in liver cirrhosis. Methods A total of 210 patients with liver cirrhosis who underwent FibroScan, color Doppler ultrasound, electronic gastroscopy, and blood biochemical examination within three days after admission to The Fifth Affiliated Hospital of Zhengzhou University from January 2017 to September 2020 were enrolled, and according to the "gold standard" of gastroscopy, the patients were divided into none, mild, moderate, and severe EGV groups. A one-way analysis of variance or the Kruskal-Wallis H test were used for comparison of continuous data between multiple groups. Receiver operating characteristic (ROC) curves were plotted for liver stiffness measurement (LSM), PC/ST ratio, and LSM+PC/ST, and the diagnostic performance of these ROC curves was compared using the Delong method. Results There were significant differences between the none, mild, moderate, and severe EGV groups in LSM ( F =32.00, P < 0.01) and PC/ST ratio ( H =49.58, P < 0.01). For the mild EGV group, LSM, PC/ST ratio, and LSM+PC/ST had an area under the ROC curve (AUC) of 0.762, 0.656, and 0.770, respectively, with a positive predictive value of 75.4%, 60.2%, and 82.5%, respectively, and a negative predictive value of 75.0%, 75.8%, and 65.4%, respectively. For the moderate EGV group, LSM, PC/ST ratio, and LSM+PC/ST had an AUC of 0.841, 0.796, and 0.896, respectively, with a positive predictive value of 86.1%, 68.0%, and 74.1%, respectively, and a negative predictive value of 79.7%, 80.5%, and 90.2%, respectively. For the severe EGV group, LSM, PC/ST ratio, and LSM+PC/ST had an AUC of 0.834, 0.830, and 0.903, respectively, with a positive predictive value of 80.5%, 71.4%, and 79.5%, respectively, and a negative predictive value of 82.5%, 83.6%, and 85.0%, respectively. PC/ST ratio and LSM+PC/ST had significantly different AUC in predicting mild, moderate, and severe EGV ( Z =2.66, P =0.007; Z =2.71, P =0.007; Z =2.37, P =0.018). Conclusion LSM, PC/ST ratio, and LSM+PC/ST have a good predictive value for moderate-to-severe EGV in liver cirrhosis.

Objective: To investigate the profiles of blood amino acid and acylcarnitine in early neonates with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and the sensitivity of newborn screening, and to explore potential biochemical metabolic markers for newborn screening program. Methods: Amino acid and acylcarnitine profiles in dried blood spots of newborn screening program were analyzed by tandem mass spectrometry (MS/MS). A total of 158 651 neonates born in Guangzhou from January 1, 2015 to June 30, 2019 were enrolled in this newborn screening program, and additionally 55 patients with NICCD confirmed by SLC25A13 gene analysis in Guangzhou Women and Children Medical Center were included in this study. NICCD screen-positive was defined as the cutoff value of citrulline (Cit) ≥ 30 μmol/L. The values of blood sampling time of the true positive group and those of the false negative group were compared by t-test. The levels of amino acid and acylcarnitine among different groups, including true positive group (Cit≥30 μmol/L), false negative group (Cit 21-<30 μmol/L and Cit<21 μmol/L) and the normal control group, were analyzed by F test, respectively. Results: Among 158 651 neonates, 39 neonates were positive for NICCD screening. Three of them were confirmed NICCD and 4 cases were found to be false negatives. The positive predictive value was 7.7% and the sensitivity was about 43.0%. Among 55 patients with NICCD, 18 cases (18/55, 32.7%) were true positives and 37 cases (37/55, 67.3%) were false negatives based on the cutoff value of citrulline in the dried blood spots for newborn screening. The blood sampling time was significantly different between true positive group and false negative group ((4.28±1.6) vs. (2.98±0.74) d, t=4.06, P<0.01). The increased levels of tyrosine((176.0±98.4) μmol/L), methionine ((37.0±26.9) μmol/L) and phenylalanine ((133.0±80.9)μmol/L) in Cit≥30 μmol/L group (n=18) were significantly different as compared with those in the other three groups, respectively (F=117.0, 58.5, 135.0, P<0.01). The levels of arginine ( (10.0±9.2) , (11.0±9.3) , (9.0±17.8) μmol/L), valine ( (119.0±29.8) , (107.6±14.1) , (102±68) μmol/L) and leucine ( (167.0±37.1) , (161.0±37.7) , (163.5±180.6) μmol/L) were not statistically significant among groups of Cit≥30 μmol/L(n=18), Cit21-<30 μmol/L(n=7) and Cit<21μmol/L(n=30,P>0.05), but they were significantly higher than those of the normal control group ((4±3), (78±21), (114.0±31.5) μmol/L, n=1 000), respectively(F=30.1, 23.0, 29.8, P<0.01). Alanine (Ala) ( (150±50) , (156.0±30.2), (168±105), (152±52) μmol/L) levels showed no significant difference (F=0.86, P>0.05) but the ratios of Ala/Cit (1.52±1.44, 6.82±1.56, 12.06±7.71, 19.42±6.27) decreased significantly among the four groups (F=69.0, P<0.05). The acylcarnitine levels showed no statistically significant results among the different groups (P>0.05). With Cit≥30 μmol/L and Ala/Cit<7.5 as cutoff values, the number of screen-positive cases reduced from 39 to 22 cases with no additional false negative case. With Cit≥21 μmol/L and Ala/Cit<7.5 as cutoff values the number of screen-positive cases increased to 117 cases with 1 additional true positive. Conclusions The profiles of blood amino acid in early neonates with NICCD present the increased levels of multiple amino acids including citrulline, tyrosine, methionine and phenylalanine, and decreased ratio of Ala/Cit. Taking citrulline and ratio of Ala/Cit as screening markers can improve the positive predictive value appropriately. The limited sensitivity of NICCD newborn screening may be related to early blood sampling time.

Objective To explore the effect of drug injection under bronchoscopy on the retreatment of smear positive cavitary pulmonary tuberculosis. Methods From June 2016 to December 2017,164 cases of pul-monary tuberculosis with smear Yang cavity type were selected,which were divided into 2 groups according to the random digital table method,each groups has 82 cases.The control group received routine treatment,the observa-tion group underwent bronchoscopy with Kangfuxin Liquid combined with drug injection therapy.The clinical effect of the two groups,the changes of lung function before and after treatment and the improvement of clinical symp-toms were compared.Results The clinical curative effect of the treatment group was better than the control group, which difference was statistically significant(P < 0.05). FEV1,FEV1/FVC,PEF index in the observation group were better than the control group,which difference was statistically significant(P<0.05).The complication rate of observation group was lower than the control group,which difference was statistically significant(P < 0.05). Conclusion Drug injection under bronchoscopy can significantly improve the clinical efficacy and lung function and promote clinical symptoms in patients with retreated smear positive pulmonary tuberculosis.It is worthy of popu-larization and application.

Objective To explore the value of time series analysis and model construction in predicting hand-foot-mouth disease(HFMD). Methods By analyzing the data of HFMD in a hospital in Zhengzhou from January 2009 to October 2016,a seasonal autoregressive moving average(ARMA)model was established according to the time series analysis. At the same time ,the model was evaluated to determine the fitting precision between the measured values and fitted values. Results After the parameter exploration ,the best fitting model was finally determined as ARIMA(1,0,1)(1,0,1)12,with a stationary R2 of 0.734,a statistic value of Ljung-Box Q(18)of 10.497,P Value of 0.725. The two curves of the fitted values and the measured values were close,suggesting that the model has good fitting ability. Conclusion Time series analysis and the seasonal ARMA model have good predictive ability in predicting HFMD.

Objective To understand the association between peripheral leukocytes telomere length (TL) and sleep in middle-aged and old adults.Methods A total of 176 middle-aged and old adults were investigated by using the Pittsburgh Sleep Quality Index and questionnaire.TL was measured by fluorescence quantitative PCR.The correlation and regression analysis between sleep and telomere length was performed.Results TL had a mean T/S ratio of 0.995 ± 0.23.There was a negative correlation between TL and age (r=-0.241,P=0.003).With increasing age,sleep quality became worse (r=-0.230,P＜0.01),the time to fall asleep became longer (r=0.227,P＜0.01),sleep duration was shorter (r=-0.486,P＜0.01),sleep efficiency became worse (r=-0.226,P＜0.01).After controlling for the effects of gender,age,marital status,income level,residence,smoking,drinking,physical exercise and disease status,multiple linear regression analysis indicated that sleep quality (β3=0.057,P＜0.01),time to fall asleep (β =-0.046,P＜0.01),sleep duration (β3=0.086,P＜0.01) were independent influencing factors of telomere length,suggesting that the people who had better sleep quality,the shorter time to fall asleep,the longer sleep time would have longer telomere length.Conclusions Sleep is a relevant factor affecting TL in middle-aged and elderly population.Good sleep may delay aging by slowing TL.We encourage to conduct health education about the importance of sleep quality in community.

Objective To compare the effects of fluid therapy by "measurement" water dispenser and routine fluid therapy on standard fluid therapy among patients with percutaneous coronary intervention (PCI) in coronary care unit (CCU). Methods A total of 204 patients with PCI were divided into observation group (n=102) and control group (n=102) by random number table. Patients in the observation group received drinking water plan according to regulatory requirements using the self-designed "measurement" water dispenser. Patients in the control group accepted nursing plan of routine drinking fluid therapy. This study compared the qualified rate of standardized drinking water, patient satisfaction, renal function and the incidence of contrast-induced nephropathy (CIN) three days after intervention between two groups. Results There were 102 (100.00%) qualified patients drinking water according to stipulations in the observation group, while there were 68 (66.67%) in the control group. The qualified rate of drinking water in the observation group was higher than that in the control group with a significant difference (χ2=38.4, P<0.01). There were two patients with contrast induced nephropathy in the observation group, and eight patients with contrast induced nephropathy in the control group (χ2=4.2,P=0.04). Conclusions The effect of fluid therapy by "measurement" water dispenser supplemented with diversified education is satisfactory among patients with PCI in CCU.

Objective To analyze the cognition and demand of the residency training program among clinical medical students to provide scientific basis for the promotion of this policy.Methods From May 24 to 25,2015,a self-designed questionnaire survey was conducted on 645 undergraduate clinical medical students,who came from Zhengzhou University,Xinxiang Medicine College,Henan University.Data of cognition and demand of the residency standardized training were statistically analyzed using SPSS 22.0 software.Enumeration data were analyzed by chi-square test and abnormal distribution data based on Wilcoxon rank sum test.Results 616 valid questionnaires were recovered.259 undergraduate clinical medical students (42.00％) did not quite understand the resident standardized training policy and 225 (36.50％) did not known the policy at all.Before and after clinical practice,the cognition of the residency standardized training had statistically significant difference (x2=87.596,P=0.000),the knowledge of the policy (x2=10.939,P=0.012) and the degree ascending alleviate employment pressure (x2=29.349,P=0.000) were the main influencing factors of the clinical medical students' choices after graduation.Conclusion Improving medical students' understanding of the significance of medical education after graduation,and the integration of professional degree training and residency standardization training effectively helps to promote implementation of the policy.

Objective To investigate the dynamic changes in the serum inflammatory cytokines and their association with neurogenic pulmonary edema (NPE) in the patients with severe hand-foot-mouth disease (HFMD).Methods Eighty-nine patients with severe HFMD from March 2010 to December 2012 were recruited in the study.The patients were divided into NPE group and central nervous system diseases (CNSD) group according whether they had NPE.The cytokines,including interleukin (IL)-4,IL-6,IL-10,IL-17,tumor necrosis factor-α (TNF-α) and interferon-γ(IFN-γ)were evaluated by using enzyme-linked immunosorbent assay on day 1,3 and 5 after admission to hospital.Risk factors for NPE involvement during hospital stay were analyzed with multivariate Logistic regression analysis.Results (1) Compared with the CNSD group,the serum levels of IL-6 (Ftime =1.876,P =0.177,Ftime* group =2.192,P =0.145,Fgroup =7.855,P =0.007),TNF-α(Ftime =13.133,P =0.001,Ftime* group =0.291,P =0.592,Fgroup =3.644,P =0.042),IL-10 (Ftime =14.580,P =0.001,Ftime* group =2.612,P =0.078,Fgroup =16.823,P =0.000),INF-γ (Ftime =3.093,P =0.045,Ftime* group =0.513,P =0.600,Fgroup =20.141,P =0.000) were significantly higher than those in NPE group.(2)The serum levels of TNF-α,IL-10,INF-γ rose to the peak on the third day.(3) By using multivariate Logistic regression analysis,age (OR =3.383,95％ CI:1.173-4.759),days of fever (OR =4.925,95％ CI:1.758-3.794),hyperglycaemia (OR =3.465,95％ CI:1.303-5.220),leucocytosis (OR =7.579,95 ％ CI:2.530-12.704) and elevation of IL-10 (OR =1.228,95 ％ CI:1.007-1.523) were entered into equation.In the risk evaluation model,these variables remained independent predictors for NPE.Conclusions Abnormal cytokine productions appear to be responsible for the pathogenesis of NPE,and might be an effective tool for predicting NPE in infants with severe HFMD.