The Author discussed some concerns and detailed thoughts that have been integrated into 8-year medical training program by using problem-based learning(PBL)method in the Biochemistry teaching.PBL is an effective method in stimulating the enthusiasm of learning,fostering the ability of problem-asking and-solving,and thus a worthwhile approach to be further carried out in high-level medical education of China.

Objective To survey the prevalence and distribution of dyskinesia and motor fluctuations, and to investigate the factors related to the dyskinesia and motor fluctuations. Methods The detailed information were recorded, patients were rated by Unified Parkinson's disease rating scald (UPDRS) and Hoehn-Yahn stage. The occurrence of dyskinesia and motor fluctuations were recorded according to UPDRS Ⅳ. Results One hundred and twenty-two patients receiving levodopa treatment for at lease 6 months were involved. Fifteen (12.3%) were experiencing dyskinesia and 41(33.6%) motor fluctuations. The age of onset(OR=0.907,P<0.01) and daily levodopa dose (95% CI 1.000-1.004, OR=1.002, P<0.05) were independent factors with dyskinesia; while the age of onset (OR=0.922, P<0.05), levodopa treatment duration (OR=1.234, P<0.05), daily levodopa dose (95% CI 1.002-1.008, OR=1.005, P<0.01) and Hoehn-Yahn stage (OR=1.869, P<0.05) were independent factors of motor fluctuations. Conclusions The rate of motor complications was lower than the results surveyed in European countries. The likelihood of occurrence of dyskinesia and motor fluctuations is increased in those on high daily levedopa dose. The concomitant use of other medication to reduce levedopa dose might delay the motor complications.

Objective To study the incidence of rapid eye movement sleep behavior disorder (RBD) and its impact on the clinical manifestations of patients with Parkinson' s disease (PD). Methods One hundred and twenty-four PD patients were included into this study and each of them was given the non motor symptoms questionnaire (NMSquest) to investigate the incidence of RBD. The PD patients were then divided into the RBD group and non RBD group, according to their answers to the NMSquest. Then the clinical differences were investigated between PD patients with and without RBD on the aspects of demographic characters, Hoehn-Yahr (H-Y) stage, the scores of Unified Parkinson Disease Rating Scale (UPDRS) sub-items, the incidence of non motor symptoms, and the dysfunctions of non motor systems (cognitive impairment, anxiety, depression and sleep disorders ). The evaluation tools of non motor functions include Mini Mental State Exam ( MMSE), Hamilton Depression Scale (HAMD), Parkins' s Disease Sleep Scale (PDSS) and Epworth Sleepiness Scale (ESS). Results ( 1 ) 62.9% (78/124) of the PD patients have been experiencing RBD. (2) The course of the disease in RBD group ( 3.8 ± 2.8 ) was significantly shorter than non RBD group (5.0 ± 2.5, t = - 1. 972, P = 0. 048 ) while the sex, age, onset age and the mode of onset, Levodopa dose equivalents (LDE) and the kinds of medicines showed no difference between the two groups. (3) H-Y stage, the scores of UPDRS sub-items and the incidence of motor complications showed no difference between RBD and non RBD group. (4) Most of the non motor symptoms, including the gastrointestinal dysfunctions, autonomic dysfunctions, mood disorders and sleep disturbances, occurred much frequently in RBD group, however, the scores of MMSE, HAMD, HAMA,PDSS and ESS showed no difference between the RBD and non RBD group. Conclusion RBD commonly occurred in PD patients, and PD patients with RBD have a tendency to suffer from dysfunction of non motor systems.

Objective To determine the prevalence of rapid eye movement(REM)sleep behavior disorder(RBD)in patients with Parkinson' s disease(PD)and to investigate the risk factors of PD-RBD and its effect on the progress of PD. Methods Using the minimal diagnostic criteria of parasomnias described in the International Classification of Sleep Disorders-Revised(ICSD-R)to diagnose clinically probable RBD(cpRBD), patients were assessed by Unified Parkinson's Disease Rating Scale(UPDRS),MMSE, Montreal Cognitive Assessment(MoCA)at baseline and followed for 2.5 years. Results The frequency of cpRBD ranged from 35.6%(47/132)to 41.7%(55/132)during the study period. 11.4% (15/132)patients dropped out from the study. Lower MoCA score and type of onset are independent factors with cpRBD; Lower MoCA score(OR =0. 817 ,P =0. 004)is the risk factor while tremor(OR =0. 247 ,P =0. 020)is the protective factor. PD in patients with PD-RBD may progress more rapidly than non PD-RBD patients(UPDRS Ⅲ change from baseline 9. 86 ± 4. 96 vs 6. 76 ± 4. 26, t = 2. 909, P = 0. 005; H-Y change from baseline 0. 77 ± 0. 54 vs 0. 33 ± 0. 49, t = 3. 664, P = 0. 000). Conclusion RBD may be a symptom predictive for rapid PD progression, declining cognition and psychosis.

Objective To explore the relationship between the interleukin-6 (IL-6) RS1800796 gene polymorphism and susceptibility of Enterovirus 71 (EV71) infection.Methods One hundred and twenty-three children with EV71 infection were selected as infection experimental group from March 2012 to December 2014 in the Central Hospital of Xiangtan,and they were divided into mild EV71 infection group (62 cases) and severe EV71 infection group (61 cases).And 52 age-and gender-matched healthy children were selected as the healthy control group.Two mL blood samples were collected from all subjects,and DNA was extracted by Beijing Optimal Boland Gene Technology LTD.The SNaPshot was used to determine the genotype for G/C polymorphism at RS1800796 position of IL-6 gene.Results The genotype frequency of IL-6 RS1800796 GG in the infection experimental group [73.2％ (90/123 cases)]was significantly higher than that in the healthy control group[48.1％ (25/52 cases)],and the difference was statistically significant (x2 =10o 215,P =0.002,OR =2.945,95 ％ CI:1.500-5.782).No significant difference was found in the distribution of genotype frequency of the IL-6 RS1800796 GG between the mild EV71 infection group and the severe EV71 infection group[71.0％ (44/62 cases)vs.75.4％ (46/61 cases),x2 =0.309,P =0.685].The G allele in IL-6 RS1800796 G/C was more frequent in the infection group (85.0％)than that in the control group (70.2％),and the difference was statistically significant (x2 =10.183,P =0.002,OR =2.399,95％ CI:1.389-4.143).No significant difference was found in allele frequency of the IL-6 RS1800796 G between the mild EV71 infection group and the severe EV71 infection group (83.1％ vs.86.9％,x2 =0.703,P =0.477).Conclusion The G allele of IL-6 RS1800796 confers susceptibility to infection of EV71.But G allele carrier will not increase the risk of severity after infection.

Objective To explore the relationship between interleukin(IL)-13 RS20541 gene polymorphism and susceptibility of enterovirus 71 (EV71) infection in children's hand-foot-mouth disease.Methods Blood samples were collected from 123 children with EV71 infection from the Central Hospital of Xiangtan (experimental group),and they were divided into mild EV71 infection group (n =62) and severe EV71 infection group (n =61) according to their severity.And 52 healthy children without EV71 infection were selected as the controls,with age and sex matched.Two mL blood samples stored in the-80 ℃ freezer,were collected from all subjects,and DNA was extracted by Beijing ubiolab genetic technology company limited.The SNaPshot was used to determine genotype for G/A polymorphism at RS20541 position of IL-13 gene.SPSS 18.0 software was used to analyze the data.Results IL-13 RS20541 loci had 3 genotypes:AA,GA,GG;the frequency of AA,GA,GG in the experimental group was 4.07％,44.71％,51.22％,which was significantly lower than that in the healthy control group (the frequency of AA,GA,GG were 11.54％,32.69％,55.77％),there was no statistically significant difference in genotypes (x2 =4.676,P ＞ 0.05);there was no statistically significant difference in allele frequency (the frequency of A,G in experimental group was 26.42 ％,73.58 ％,and that of the healthy control group was 27.88 ％,72.12 ％;x2 =0.080,P ＞ 0.05).EV71 infection caused by mild group,severe group and healthy controls genotype frequencies between the 3 groups [(AA + GA) were 53.22％,44.26％,44.23％;GG were 46.78％,55.74％,55.77％;x2 =1.294,P ＞ 0.05] and allele frequency (A were 30.65％,22.13％,27.88％;G were 69.35％,77.87％,72.12％;x2 =2.349,P ＞ 0.05) among the mild group,severe group and healthy control group had no statistical significance.Conclusion There is no correlation between the IL-13RS20541 gene polymorphism and EV 71 infection in children with the hand-foot-mouth disease.

Objective To assess the development,progression and change of nonmotor symptoms in patients with Parkinson' s disease and its impact on patients' quality of life.Methods Eighty-seven consecutive patients with idiopathic Parkinson' s disease were studied.Parkinsonian status was assessed at baseline and 3 years follow-up using Unified Parkinson' s Disease Rating Scale (UPDRS) part Ⅲ & Ⅳ,Nonmotor Symptoms Questionnaire (NMSQuset),Parkinson-related quality of life (PDQ) scales.Paired ttest,Chi-square test,Spearman rank order correlation and hierarchical regression of the major statistical procedures were employed.Results At 3 years follow-up,compared to baseline,the UPDRS Ⅲ score (22.21 ±11.31 vs 30.49± 11.68),UPDRS Ⅳ score(1.00±1.54 vs 2.94±3.12),NMS score (7.98±3.96 vs 12.35 ± 5.12) and PDQ score (28.11 ± 22.88 vs 36.65 ± 26.95) were significantly higher ( t =- 5.54,- 5.75,- 6.46,- 5.29,all P =0.000,respectively).The aggravation of motor and nonmotor symptoms caused the decline of quality of life.The prevalence of constipation,problem of remembenng thing,nocturia ranked tops,and depression,and anxiety were still in the middle,compared with baseline.The prevalence of pains,sweating,dribbling,sense of incomplete emptying etc were significantly increased during the follow-up,△R2 were 21.6％ and 23.4％ respectively,resulting in the deterioration of quality of life.Conclusions PD nonmotor symptoms appear from the early stage.The motor and nonmotor symptoms aggravate over time.

Objective To observe progression of motor symptoms and occurrence of motor complications in parkinsonian patients and investigate the rate of progression of motor symptoms and risk factors of motor complications.Methods One hundred and thirty patients diagnosed with PD in 2007 in Department of Neurology,Xinhua Hospital were followed up for 3 years.The Unified Parkinson' s Disease Rating Scale (UPDRS) and H-Y staging were used to assess and follow up motor symptoms and occurrence of motor complications,and analyze the rate of progression of motor symptoms and risk factors of motor complications with statistics.Results ( 1 ) Mean annual growth in H-Y staging was 2.5％,and UPDRS motor scores was 3.1％ ; the incidence of dysphagia at endpoint in patients was increased by 23.0％ compared with baseline; incidence of falls was increased by 16.7％;(2)Daily levodopa dose at endpoint ( OR =1.004,95％ CI 1.001—1.006,P =0.008 ) was independent risk factors with dyskinesia; While duration ( OR =1.637,95％ CI 1.083—2.473,P =0.019 ),levodopa treatment duration ( OR =0.698,95％ CI 0.494—0.987,P =0.042 ),daily levodopa dose at haseline ( OR =1.005,95％ CI 1.001—1.010,P =0.016) and at endpoint ( OR =1.014,95 ％ CI 1.001 —1.027,P =0.032 ) were risk factors with motor fluctuations.Conclusions As the disease progresses,motor function in parkinsonian patients gradually worsens,the incidence of swallowing difficulty and of falls is increased,and the incidence of motor complications is increased.The total exposure to levodopa in parkinsonian patients is predictor for motor complications.

Objective To derive a questionnaire to assess the risk of developing motor complications through a 3-year prospective investigation on 71 patients of Parkinson' s disease (PD) in the out clinic at our hospital.Methods Three years after the first assessment,71 PD out patients were reassessed using various scales,including Unified Parkinson Disease Rating Scale,Hoehn-Yahr grade,Mini Mental State Exam,Hamilton Depression Scale and Hamilton Anxiety Scale.Results The incidence of motor complications was 43.6％ (31/71).Logistic regression analysis showed that the prognostic factors for motor fluctuation were age of onset ≤ 54 (OR =6.4,95％ CI 1.7-24.5,P =0.006),the occurrence of swallowing difficulty (OR =3.8,95 ％ CI 1.0-14.1,P =0.04) and depression (OR =4.0,95 ％ CI 1.1-13.7,P =0.03),and the prognostic factors for dyskinesia were age of onset ≤54 (OR =48.5,95％ CI 1.9-121.0,P:0.02),the occurrence of falling (OR =64.1,95％ CI 2.9-142.2,P =0.008) and the daily levodopa dosage ＞ 600 mg(OR =17.5,95％ CI 1.1-276.2,P =0.04).Based on the regression model,the assessment questionnaire for motor complicationsincludes the followings:the questionnaire for motor fluctuations:the age of onset ≤54,2 points; the occurrence of swallowing difficulty,1 point; the occurrence of depression,1 point; the questionnaire for dyskinesia:the onset age ≤54,2 points; the occurrence of falling,3 points; daily levodopa dosage ＞ 600 mg,2 points.In all patients in this study,21.7％ (10/46) was asscssed to a total scorc of 0-1 which is associated with a low risk of motor fluctuation,8/16 had a score of 2 which is associated with intermediate risk and 8/9 got a score of 3-4 associated high risk; 10.2％ (5/49) had a score of 0-2,a low risk of dyskinesia,4/13 had a score of 3-4,a intermediate risk and 7/9 got a score of 5-7 which is associated with a high risk.Conclusions Age onset ≤54,the occurrence of swallowing difficulty,falling and depression,daily levodopa dosage ＞ 600 mg were considered to be the prognostic factors of motor complications in PD.The questionnaire may help to stratify PD patients into low-risk,medium-risk and high-risk groups for motor complications and the higher the score in the questionnaire is related to the higher risk of motor complications.

Objective To investigate the influencing factors for low-level viremia (LLV) and their dynamic changes in chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogues (NAs) for the first time. Methods A retrospective analysis was performed for 78 CHB patients who attended Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, from November 2020 to March 2022 and received antiviral therapy with NAs for at least 12 months, and according to HBV DNA level during treatment, they were divided into sustained virologic response (SVR) group with 58 patients and LLV group with 20 patients. The independent samples t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the independent influencing factors for LLV and establish a predictive model, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of this model. The Kaplan-Meier method was used to analyze cumulative HBV DNA negative conversion rate, and the Log-rank test was used for comparison. The analysis of variance with repeated measures was used to analyze the differences in HBV DNA and HBsAg between the two groups or within each group at weeks 0, 12, 24, 36, and 48. Results Compare with the SVR group, the LLV group had significantly higher HBeAg positive rate (90.0% vs 48.3%, χ 2 =10.701, P =0.001), log(HBV DNA) value (7.26±1.46 vs 5.65±1.70, t =-4.178, P < 0.001), and log(HBsAg) value (4.53±0.86 vs 3.44±0.93, t =-4.813, P < 0.001) and significantly lower age [29 (26-34) vs 33 (30-43), Z =-2.751, P =0.009], alanine aminotransferase (ALT) [67.0 (54.0-122.0)U/L vs 111.0 (47.0-406.0)U/L, Z =-2.203, P =0.028], aspartate aminotransferase [43.5 (32.8-62.8) U/L vs 77.5 (35.0-213.0)U/L, Z =-2.466, P =0.014], and liver stiffness measurement [7.7 (6.3-8.5)kPa vs 8.9 (7.2-11.4)kPa, Z =-2.022, P =0.043]. The multivariate logistic regression analysis showed that baseline HBV DNA (odds ratio [ OR ]=2.365, 95% confidence interval [ CI ]: 1.220-4.587, P =0.011), HBsAg ( OR =4.229, 95% CI : 1.098-16.287, P =0.036), and ALT ( OR =0.965, 95% CI : 0.937-0.994, P =0.018) were independent influencing factors for LLV in CHB patients, and the predictive model of Logit(MLLV)=-8.668+1.441×lgHBsAg+0.598×lgHBV DNA-0.016×ALT was established based on these factors, which had a larger area under the ROC curve than HBV DNA, HBsAg, and ALT (0.931 vs 0.774/0.856/0.666), with a sensitivity of 85.00% and a specificity of 93.10% at the optimal cut-off value of 0.44. The CHB patients with baseline HBV DNA > 7.29 lgIU/mL or HBsAg > 4.38 lgIU/mL had a significantly lower DNA negative conversion rate than those with DNA ≤7.29 lgIU/mL or HBsAg ≤4.38 lgIU/mL ( χ 2 =22.52 and 26.35, both P < 0.001). In the CHB patients, the highest reduction rates of HBV DNA and HBsAg were observed at weeks 12 and 24, respectively, and the LLV group had significantly higher levels of HBV DNA and HBsAg than the SVR group at weeks 0, 12, 24, 36, and 48 (HBV DNA: t =-4.084, -4.526, -5.688, -7.123, and -6.266, all P < 0.001; HBsAg: t =-4.652, -4.691, -4.952, -4.804, and -4.407, all P < 0.001). Conclusion For the CHB patients treated with NAs for the first time, those with high HBV DNA load, high HBsAg quantification, and low ALT level at baseline are more likely to develop LLV, and dynamic monitoring of these indices is of great significance to observe the onset of LLV.