Objective The aim of this study was to explore the natural history of Alzheimer's disease(AD)based on the multi-state Markov model and to provide methodological reference for the chronic diseases.Methods Based on the American public database ADNI,we constructed a three states Markov model to estimate the transition intensity,transition probability,influencing factors and sojourn time of different states.Survival curves and goodness of fit was obtained.Results Gender,age,FAQ,MMSE,CDRSB,ADAS13 and TMT-B-Time were important influencing factors in the natural history of AD.The mean sojourn time of NC and MCI was 7.502 and 11.621 years,respectively.Model fit can be accepted.Conclusion Multi-state Markov model has a good application value for the outcome prediction of multi-state chronic diseases such as AD.

Objective The shared random-effect model(SREM)was applied to study the reversion of mild cognitive impairment(MCI)to normal cognition(NC),to compare the predictive performance of different longitudinal cognitive markers for the reversion,and to evaluate the covariate effects of predictors.Methods The SREM model consisted of two sub-models:the longitudinal sub-model adopted linear mixed model to describe different longitudinal cognitive markers trajectories;and the survival sub-model used proportional risk model to fit the survival process.Goodness of fit was based on the log-likelihood value,and information criterion.AUC(area under the curve)was used to evaluate the predictive performance of different longitudinal cognitive markers,including MMSE,CDRSB,FAQ,ADAS11,ADAS13 and ADASQ4.Results There were 72(8.54%)of 843 patients with MCI reversed to NC at the end of follow-up.The log-likelihood value of the SREM model based on spline-PH-GH parameter distribution was the largest,and AIC and BIC were the smallest;the SREM model based on CDRSB score as longitudinal cognitive marker had the best fitting performance,with high AUC values at different times ranging from 0.797 to 0.852,and the lowest prediction error,ranging from 0.0427 to 0.0429.Age,gender,education level,marital status and APOEε4 gene affected the cognitive function and daily activity function.Six different longitudinal cognitive markers influenced the reversion.Conclusion CDR score was the best predictor of cognitive function and the reversion in MCI patients.Cognitive function and daily activity function can be used as dynamic monitoring indicators of MCI reversion.

Objective The joint latent class model(JLCM)was applied to study the reversion of mild cognitive impairment(MCI)to normal cognition(NC),providing a methodology reference for the longitudinal study of chronic diseases.Methods The JLCM model consisted of three sub-models:the latent class sub-model adopted multi-class logistic regression to estimate the latent classes;the longitudinal process sub-model adopted linear mixed model to describe the longitudinal cognitive measurement;and the survival process sub-model adopted proportional risk model to fit the cognitive process.Goodness of fit was based on information criterion,posterior classification,comparison between predicted value and observed value and conditional independence assumption.Results The MCI population was divided into two latent classes based on the JLCM model,including 783(92.88%)and 60(7.12%),respectively.The latent class sub-model showed that gender,marital status,APOE4 and FAQ had statistical significance for the determination of latent classes.The longitudinal process sub-model showed male(β=-0.685,95%CI:-1.144,-0.226),being single(β=0.743,95%CI:0.200,1.286),not carrying APOE4(β=-1.201,95%CI:-1.636,-0.766)and without functional impairment(β=-1.868,95%CI:-2.095,-1.641)had higher MMSE scores.The survival process sub-model showed that high education level(HR=1.264,95%CI:1.134,1.395),being single(HR=1.593,95%CI:1.286,1.899)and not carrying APOE4(HR=0.453,95%CI:0.043,0.862)were protective factors for reversion to NC in MCI patients.Conclusion JLCM model has good application value in the study of chronic diseases such as cognitive impairment.

Objective:To investigate the application value and treatment opportunity of single balloon enteroscopy in children with Peutz-Jeghers syndrome(PJS).Methods:A retrospective analysis was conducted on 33 children diagnosed with PJS in Hunan Children′s Hospital from January 2011 to September 2021.The patient′s age, gender, family history, clinical symptoms, enteroscopy examination and treatment, number of polyps, intraoperative and pos-toperative complications, surgical treatment, recurrence of surgery, and follow-up data were analyzed, and the chi- square test was used for statistical analysis. Results:A total of 33 PJS children aged (9.00±3.13) years, including 21 males and 12 females, were included.All of them received at least once single balloon enteroscopy test.The main manifestations of the children were black spots (33 cases) and multiple polyps in the digestive tract (31 cases). In all the 33 cases, black spots were distributed on lips.Some black spots were also found at the end of fingers (3 cases), at the end of foot toes(2 cases), and at the end of finger toes (6 cases). During the operation, 391 polyps were removed, most of which were jejunum polyps (37.08%, 145/391 polyps). Eleven children with PJS has intussusception, of which intestinal intussusception accounted for 90.91% (10/11 cases). Ten cases (30.30%, 10/33 cases) received surgical treatment, and 72.73% (8/11 cases) underwent surgery for acute refractory intussusception.One case had intestinal perforation and 2 cases were bleeding during the operation, and the 3 cases recovered completely after hemostatic clip sealing and surgical treatment.The incidence of hollow ileum polyps and giant polyps in children aged >8 years was higher than that in children aged ≤8 years[92.55% (149/161 polyps) vs.7.45%(12/161 polyps), 96.20%(76/79 polyps) vs.3.80% (3/79 polyps)]. The differences were statistically significant ( χ2=9.854, 8.711, all P<0.05). There was no significant difference in the incidence of intussusception among different age groups ( P>0.05). Among the 33 children with PJS, 57.58% (19/33 cases) had recurrence 1-3 years after operation, and no cases of cancer have been followed up so far. Conclusions:Intestinal polyps are common in children with PJS, and the application of single-balloon enteroscopy in children with PJS is reliable and safe.Children over 8 years old are more vulnerable to empty ileum polyps and giant polyps.Therefore, it is advised that children aged above 8 years with PJS should undergo at least once enteroscopy.

Objective:To study parameters of MRI image in different tissue differentiation,cell type of primary liver cancer.Methods:The pathological results and MRI data of regeneration nodules (27),hepatocellular carcinoma (HCC) (81 total;15,highly differentiated;40,moderately differentiated;26,low-grade differentiation),intrahepatic cholangiocarcinoma (ICC) (20) were retrospectively analyzed and compared To compare the difference of ADC values,strengthen degree among the regeneration nodules,HCC and ICC,and among HCC tissue differentiation.Results:Most cases of primary liver cancer can be accurately diagnosed by conventional MRI combined with LAVA.there are statistically significant differences of ADC values among regenerative nodules,HCC,ICC (P＜0.01),and among highly,moderately,poorly differentiated HCC groups (P＜0.01).But there is not actual clinical significance of the ADC values between moderately and poorly HCC.there is no statistically significant difference of the ADC values between highly differentiated HCC and ICC (P=0.27).Conclusion:Conventional MRI combining with DWI,LAVA can help distinguish the primary liver cancer differentiation degree and the cell type.

Objective To analyze the clinical efficacy of pre-extensive drug resistant tuberculosis (pre-XDR-TB), and to explore the feasibility of using the standard multidrug resistant tuberculosis (MDR-TB) therapeutic regimen to treat the patients with pre-MDR-TB. Methods A retrospective analysis was made for 126 cases of the MDR-TB patients who were received the treatment in Guangzhou chest hospital from 2009 to 2013. It was divided into MDR-TB group, pre-XDR-TB group and XDR-TB group according to the drug sensitive test (DST) of quinolone(levofloxacin, moxifloxacin) and aminoglycoside (amikacin). All patients were treated for 6-months with the standard therapeutic regimen including Am(Cm), Lfx(Mfx), Pto, PAS and PZA. Results (1) There were 126 cases of the MDR-TB patients in the study, 31 cases (24.6%) complicate with aminoglycosides-resistance, 69 cases (54.7%) complicate with quinolone-resistance. (2) The negative rate of MDR-TB group, pre-XDR-TB group and XDR-TB group was 82.0%, 55.8% and 29.2% respectively (χ2 = 20.110, P < 0.001). (3)The negative rate of pre-XDR-TB group significantly lower than MDR-TB group (χ2 = 8.146, P = 0.004). The negative rate of pre-XDR-TB group higher than XDR-TB group (χ2= 4.661, P = 0.031). Conclusions The situation of quinolone and aminoglycoside resistance was high in the patients with MDR-TB. We should carry out the detection of quinolone and aminoglycoside resistance in clinical treatment. The clinical efficacy for the patients with pre-XDR-TB was significantly poorer than the patients with MDR-TB using the standard MDR-TB therapeutic regiment treated.

Objective To study the correlation of PAZ with anti-tuberculosis treatment regimen and drug-induced liver injury in tuberculosis patients with HBV-DNA positive in order to provide an optimized treatment regimen. Methods from Jan 2013 to Dec 2014, 199 pulmonary tuberculosis with HBV-DNA positive patients and 103 pulmonary tuberculosis patients without HBV in our hospital were collected. They were assigned as follows:122 cases were anti tuberculosis treatment with antiviral therapy,64 cases were A(HRZE),58 cases were B (HRE). 77 cases were anti tuberculosis treatment but not antiviral therapy , 41 cases were C (HRZE), 36 cases were D(HRE) and 103 patients without HBV were E (HRZE, the contrast group). We had observed the liver injury for 2 months after the treatment. Results 1.Incidence of liver injury was 34.38% in group A , higher than the cases in group B(20.69%,P > 0.05). 2.Incidence of liver injury in group C was apparently higher than in group D (73.17% vs. 30.56%,P < 0.05). 3.Incidence of liver injury in group B was lower than group D (20.69% vs. 30.56%,P > 0.05)4.Incidence of liver injury in group A was lower than group C (34.38% vs. 73.17%,P < 0.05).5. Incidence of liver injury in group A was higher than group E (34.38% vs. 17.48%,P< 0.05)and there was no difference between group B and group E (20.69% vs. 17.48%,P> 0.05). Conclusion Although anti tuberculosis treatment combined with antiviral therapy can be partially reduce the incidence of liver injury and relieve the severity of liver injury in tuberculosis patients infected with HBV , but PZA toxicity to hepatocytes is a major risk factor for liver injury , and we need to change the treatment plan to reduce the occurrence of liver injury.

Objective To explore the effects of nurse-physician collaboration model on anxiety, depression and quality of life (QOL)of patients undergoing concurrent chemo-radiotherapy.Methods A total of 1 80 eligible patients from December 201 3 to December 201 4 were randomly divided into study group (n =96) and control group (n =84).The patients of study group received nurse-physician collaboration nursing,while the patients of control group received routine nursing.The self-rating anxiety scale (SAS ),self-rating depression scale (SDS ) and European organization for research and treatment of cancer quality of life questionnaire-3.0 (EORTC QLQ-C30)were used to investigate the differences between groups before and after intervention.Results Anxiety and depression in study group were better than those in control group after treatment,and the difference was statistically significant (P <0.05).Overall health,emotional function,social function,cognitive function,role function,pain,insomnia and breathing difficulties were better in study group than those in control group after treatment (P <0.05).Conclusions Nurse-physician collaboration model can improve the anxiety,depression and QOL of patients receiving chemoradiotherapy.

Objective To investigate the effects of different liver protective drugs on preventing liver injury induced by anti-tuberculosis drugs. Methods Retrospective analysis was made on 355 patients with primary pulmonary tuberculosis during intensified time. The patients received silibinon and bicyclol to prevent liver injury. 82 patients with TB were treated as control group during the same time. Results The number of patients with liver injury in silibinon group and bicyclol group were 16 cases (14.7%) and 55 cases (22.4%) respectively. The number of control group with liver injury was 9 cases (11.0%) (χ2 = 3.627,P > 0.05). The liver injuries within 4 weeks were mainly counted in. There is no difference between intervention and control groups(χ2 = 0.414,P > 0.05). There is no difference between three groups in liver injury degree (U = 0.288,P> 0.05). Conclusion Without high risk factors, anti-inflammatory and enzyme reduction drugs have no significant protective effects on liver injury caused by anti-tuberculosis drugs.

Objective To investigate the effects of 14-3-3 phosphorylation (p-14-3-3) induced by C-Jun N-termi-nal kinase (JNK) on ischemic brain injury in rats. Methods Twenty rats were divided into 4 groups:sham operation group, ischemia-reperfusion group, SP600125 group and solvent control group. The rat model of cerebral ischemia was established. The p-14-3-3, the binding of 14-3-3 and Bax and the protein expression of Bax in cytoplasm and mitochondria in hippo-campal CA1 region were detected by immunoprecipitation (IP) and immunoblotting 12-hour after ischemia-reperfusion in four groups. Results Compared with the sham operation group, protein expression levels of p-14-3-3 in cytoplasm and Bax in mitochondria were significantly increased, the binding of 14-3-3 and Bax was significantly decreased in ischemia-re-perfusion group, solvent control group and SP600125 group. The protein expressions of p-14-3-3 and Bax were significantly lower in SP600125 group than those of ischemia-reperfusion group and solvent control group. The binding of 14-3-3 and Bax was significantly higher in SP600125 group than that of ischemia-reperfusion group and solvent control group (P <0.05). Conclusion 14-3-3 phosphorylation induced by JNK plays important effects on ischemic brain injury in rats.