Objective To summarize the clinical and laboratory features of chronic manganese poisoning. Methods A retrospective analysis was conducted on the clinical data of 4 cases with chronic manganese poisoning, including gener?al information, medical history, clinical manifestations, laboratory examination such as electrophysiological and imaging. Results Patients with chronic manganese poisoning mainly presented with mild mental disorder and autonomic nerve dis?order during early stage and then gradually developed extrapyramidal symptoms and signs. The laboratory examination of chronic manganese poisoning lacked of specificity. EMG showed neurogenic damage in 3 cases and normality in 1 case. EEG showed slightly increased full guide slow wave in 1 case and normality in 3 cases. cranial MRI revealed the damag?es in bilateral symmetry of the basal ganglia nuclei in 4 cases of Chronic manganese poisoning. There was no significant correlation between the changes of urinary manganese level before or after treatment and the clinical manifestations. Conclusions Although there is lack of specific clinical manifestations of chronic manganese poisoning, the possibility of this disease should be considered when patients with mild mental disorders or autonomic nerve disorder with or without extrapyramidal symptoms. The main treatment of chronic manganese poisoning includes excretion of manganese, symp?tomatic and supportive treatment. Patients usually have the sequelae of tremor, muscle tension, and other symptoms.

Objective:To investigate the expression levels and internal relations of matrix metalloproteinase-9(MMP-9), interleukin(IL)-1β and tissue inhibitor of metalloproteinase-1(TIMP-1) within 24 h after cerebral hypoxia and ischemia(HI) in neonatal rats.Methods:SD rats aged 7 days were randomly divided into HI group( n=40), and sham operation group(sham group, n=40). The HI models were established and divided into 5 subgroups with those at 8 cases in each group at 5 postoperative time points(0, 4, 8, 12, 24 h). Pathological changes of cerebral cortex were observed by HE staining, and the expressions of MMP-9, IL-1β and TIMP-1 were detected by Western blot and RT-PCR.In addition, the hypoxia models of mouse hippocampal neuron HT22 cells were established.With adding MMP-9 inhibitor and MMP-9 agonist, the relations among MMP-9, IL-1β and TIMP-1 were further confirmed. Results:Slight nuclear abnormalities and cell body swelling occurred in cerebral cortex at 4 h after HI, and neuronal eosinophilic changes were most obvious at 12 h. Compared with those at 8 h and 12 h, the expressions of MMP-9 and IL-1β at protein and mRNA level significantly increased at 24 h after HI( P<0.01). While MMP-9 inhibitor was added to HT22 cells under hypoxia at 4 h, IL-1β mRNA expression was down-regulated. Conclusion:In the early stage of hypoxic ischemic encephalopathy in newborn rats, the expressions of MMP-9 and TIMP-1 are time-dependent.Inhibition of MMP-9 expression could reduce the level of Interleukin-1β.

Objective To investigate the expressions of insulin receptor substrate-1 (IRS-1) and insulin receptor sub-strate-2 (IRS-2) in adipocytes during catch-up growth in neonatal rats with intrauterine growth restriction (IUGR) and their correlations with the insulin resistance. Methods Sprague-Dawley rats (clean grade) were randomly divided into control group and food-restricted group after fertilization. Food-restricted group were received about 30%of food amount consumed in control group every day through the whole pregnant period to establish IUGR animal model, and were fed increased amount of breast-milk from postnatal day 1 to 21 to establish the period of catch-up growth in IUGR animal model (IUGR-CG). Fasting serum glu-cose, insulin and triglyceride were measured in blood from heart ventricles of 4-week old SD rats and insulin resistance index was calculated. Pre-adipocytes and mature adipocytes were obtained from SD rats at different age (1-week, 3-week, 5-week and 7-week old) and the former were induced to differentiate toward mature adipocytes. The levels of IRS-1, IRS-2 in the two kinds of mature adipocytes were detected by Real-Time PCR and Western blot. Results The expression levels of IRS-1, IRS-2 mRNA in mature adipocytes of IUGR-CG rats were signiifcantly lower than those of IUGR rats at 5-weeks and 7-weeks old (P<0.05) while the ex-pression levels of IRS-1, IRS-2 mRNA in differentiated adipocytes of IUGR-CG rats were signiifcantly lower than those of IUGR rats at 5-weeks old (P<0.05). The expression levels of IRS-1, IRS-2 protein in two kinds of adipocytes (mature and differentiated adipocytes) of IUGR-CG rats were signiifcantly lower than those of IUGR rats from postpartum week 1 through 7 (P<0.05). Conclusions IRS-1 and IRS-2 expression levels are downregulated in adipocytes during catch-up growth of IUGR rats, which may be closely related with insulin resistance.

[Objective] To summarize Dr. SHEN Yiping's clinical experience of integrated traditional Chinese and western medicine in treating elderly acute myeloid leukemia (AML). [Methods]By examining with cases of illness and warding round,collecting the medical records of elderly AML patients treated by Dr. SHEN, learning the latest diagnosis and treatment guidelines, reading a large number of related papers and a large number of classical books, from the aspects of etiology and pathogenesis, therapeutic principles and methods, the clinical experience of the treatment of elderly AML were analyzed and summarized, and one medical record was provided.[Results]Dr. SHEN believes that the pathogenesis is deficiency syndrome accompanied with excess syndrome. Mostly due to congenital deficiency and poor basic functions, deficiency of spleen and kidney, heat poison intrusion, burning Jin as sputum, forcing blood going in wrong line, phlegm and blood stasis, evil accumulating in bone marrow and then suffered. Dr. SHEN uses heat-clearing, detoxifying and anti-cancer drugs to suppress and eliminate leukemia cells on the basis of chemotherapy and supplements beneficial drugs to achieve the goal of chemotherapy without harming the positive effect, he uses "Kangbai Yannian Tang" combined with decitabine and chemotherapy as a basic solution and changes flexibly by according to the clinical manifestations, changes of syndrome types of the patients, the clinical effect is remarkable, and the case had good results. [Conclusion]Dr. SHEN is good at integrated traditional Chinese and western, combining of syndrome differentiation and disease differentiation, using the combination of heat-clearing method and complement in the treatment of elderly AML, the experience and wonderful methods are worth learning and spreading.

Objective:To investigate the potential mechanism of microRNA (miRNA) in hepatitis B virus (HBV) infection.Methods:The peripheral blood samples were collected from four chronic hepatitis B (CHB) patients who visited Mengchao Hepatobiliary Hospital of Fujian Medical University in 2017, and those were also collected from four healthy controls. Affymetrix GeneChip microRNA 4.0 was applied to detect the expressions of miRNA between CHB patients and healthy controls. The CHB relative differential expressions of miRNA were obtained. The functions of CHB relative miRNA were analyzed by the combination of bioinformatics tools and public database data.Results:A total of seven miRNA were differentially expressed in the peripheral blood of CHB patients. Among them, miRNA-122-5p (log 2 fold change (log 2FC)=7.78, P=0.007 3), let-7c-5p (log 2FC=3.52, P=0.019 6), miRNA-6794-5p (log 2FC=1.15, P=0.033 2), and miRNA-1226-5p (log 2FC=0.68, P=0.034 3) were up-regulated, while miRNA-619-5p (log 2FC=-1.83, P=0.002 6), miRNA-1273g-3p (log 2FC=-2.69, P=0.025 1), and miRNA-4440 (log 2FC=-3.99, P=0.047 8) were down-regulated. Further analysis showed that these miRNA could directly interact with HBV gene sequence and impact the replication of the virus. Among them, miRNA-122-5p, miRNA-6794-5p and miRNA-1226-5p could negatively regulate target genes expression to influence the formation of ficolin-1 rich granule, ficolin-1 rich granule lumen, podosome and membrane ruffle, which participated in the cell membrane movement and cell-matrix adhesion. Conclusion:MiRNA could impact the molecular movement in the cell membrane and facilitate HBV entry to liver cells, playing an important supporting role in HBV infection process.

Objective To investigate the baseline independent prognostic factors for 24 months survival of hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) patients treated with telbivudine.Methods The prospective cohort study was conducted in HBV-associated ACLF patients who were hospitalized in Mengchao Hepatobiliary Hospital of Fujian Medical University and volunteered to be treated with telbivudine for more than 24 months.The patients were observed for survival at month 1,3,6,12,and 24 after treatment.The baseline biochemical index,coagulant function,model for end-stage liver disease (MELD) score,HBV DNA level as well as comorbidities were analyzed in this study.The count data were compared with kappa test or Fisher's exact test.For the normal distributed measurement data,the homogeneity test of variances (Levene test) was firstly used for comparison between groups.Further,the group t test was applied for variance homogeneity,while the approximate t test was applied for variance non-homogeneity and the Mann-Whitney U test was applied for the non-distributed measurement data.Results A total of 41 patients were enrolled,including 3 drop-outs and 38 accomplishments.Among these 38 patients,there were 3 females (7.9 ％) and 35 males (92.1％),with ages (38.5 ± 11.1) years.There were 32 patients alive and 6 dead during 1 month's follow-up,while baseline MELD score was the independent prognostic factor (RR=1.864,95％CI:1.151-3.019) for survival.There were 31 patients alive and 7 dead during 3 months' follow-up,while baseline MELD score and upper gastrointestinal hemorrhage (UGH) were the independent prognostic factors (RR =2.053,95％CI:1.163-3.625;RR=394.939,95％CI:1.880-82 948.817).There were both 26 patients alive and 12 dead during 6 and 12 months' follow-up,while baseline MELD score was the independent prognostic factor (RR=1.761,95％ CI:1.230-2.523).At the end of 24 months' follow-up,there were 15 patients alive and 23 dead.Viral rebounds were observed in 6 patients and 3 of them were dead.Baseline HBV DNA level,MELD score and electrolyte imbalance were the independent prognostic factors (RR-9.722,95％ CI:1.607-58.821;RR=l.518,95％ CI:1.066-2.162;RR=87.505,95％ CI:2.263-3 384.232) for 24 months'survival.Conclusions Although telbivudine is not recommended as the first-line treatment,ACLF patients with low MELD score and low HBV DNA level at baseline,individualized treatment may improve patient's survival rate.UGH and electrolyte imbalance may affect the efficacy of telbivudine and reduce the survival rate of ACLF patient.

Objective To investigate the clinical features of Parkinson disease (PD)with constipation.Methods From October 2013 to August 2015,a total of 204 PD patients were consecutively recruited from the Departments of Geriatrics and Neurology,Beijing Tiantan Hospital,Capital Medical University,and were evaluated by Rome Ⅲ diagnostic criteria for functional constipation and other related scales of motor symptoms(MS)and non-motor symptoms(NMS),the activity of daily living(ADL)and quality of life.Results Overall,131 of 204(64.2％)PD patients with constipation were assigned to the PD-C group and 73 of 204 (35.8％)PD patients without constipation were assigned to the PD-NC group.In the PD-C group,38 of 131(29％)PD patients had constipation before motor symptoms occurred.The mean age and age of onset in the PD-C group were significantly older than those in the PD-NC group (64.13 ± 9.67 vs.58.35 ± 11.37;60.07 ± 10.46 vs.55.10±12.97;F=2.287,4.948;t=3.827,-2.788;P＜0.01 for both).Meanwhile,compared with the PD-NC group,the PD-C group was associated with dramatically longer disease duration (2.25,range:1.00-5.00 vs.2.00,range:1.00-3.13;Z =-2.254;P ＜ 0.05),increased scores of the Unified Parkinson Disease Rating Scale (UPDRS) Ⅲ (26.00 scores,range:18.00 37.50 vs.19.00,range:12.50-31.00;Z =-2.349,P ＜ 0.05),more advanced stages on the Hoehn-Yahr (H-Y) scale (2.00 stage,range:1.50-2.50 vs.1.50,range:1.00-2.50;Z=-2.334,P＜0.05),higher total numbers of NMS(11.00,range:6.00-15.00 vs.6.00,range:3.00-11.00;Z=-3.715,P＜0.05),and higher numbers of NMS occurring before and after MS(before,2.00,range:0.00-4.00 vs.1.00,range:0.00-2.00;after,8.00,range:3.00-14.00 vs.5.00,range:2.00-9.50;Z =-2.612,-2.630,respectively;P＜0.05 for both).Additionally,there were significant differences between the groups in the scores of the Hamilton depression scale (HAMD),the Hamilton anxiety scale (HAMA),the Pittsburgh sleep quality index (PSQI),the scales for outcomes in Parkinson disease-autonomic (SCOPA-AUT),the Fatigue severity scale (FSS),the Apathy scale,the Montreal Cognitive Assessment(MoCA)scale,the UPDRS Ⅱ and ADL Scale,and the PDQL-39 (all P＜0.05).Binary Logistic regression analysis showed that age,SCOPA-AUT,HAMA and HAMD were risk factors for PD-C(OR=1.091,1.107,1.10 and 1.080;P＜0.05 for all).Conclusions PD patients have a high incidence of constipation,and more than a quarter of patients have constipation before MS occurs.Meanwhile,PD patients with constipation are usually associated with old age and late age of onset,long disease duration,severe MS,frequent and severe NMS,bad cognition,emotional state and sleep,severe fatigue,and apathy.Moreover,advanced age,autonomic dysfunction,anxiety and depression increase the risk of PD with constipation.Constipation has a serious negative impact on the activity of daily living and quality of life in PD patients.

Virtual reality is an integrated technology which simulates the real world via the computer, with characteristics of immersion, interaction and imagination. It is widely used in neurological rehabilitation. Freezing of gait (FOG) is a destructive symptom which appears in late stage of Parkinson's disease, which can be divided into subtypes of moving forward with very small steps, leg trembling in place and total akinesia, and often results in fall and injury of the patients. Virtual reality can simulate the environment of FOG to provide a new idea for the assessment. Virtual reality combined with treadmill training can provide challenging functional training in a complex environment to improve the gait. How it works is remained unclear.

Objective To investigate the risk factors for short-term prognosis in patients with HBV-related acute-on-chronic liver failure (ACLF). Methods A retrospective analysis was performed for the clinical data of 119 patients with HBV-related ACLF who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from October 2019 to October 2020, and according to their survival status on day 90, they were divided into death group and survival group. The patients were given antiviral therapy with entecavir or tenofovir. Related clinical data were collected, including alanine aminotransferase (ALT), aspartate aminotransferase, cholinesterase (ChE), albumin (Alb), cholesterol, alpha-fetoprotein, and HBV DNA at baseline, as well as the incidence rate of important complications. Model for End-Stage Liver Disease (MELD) score was also calculated. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-squared test was used for comparison of categorical data between two groups; a logistic regression analysis was used to investigate the influencing factors for the 90-day prognosis of patients with HBV-related ACLF and establish a new predictive model; the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of the new model in predicting the prognosis of HBV-related ACLF. Results Of all patients, 33 died within 90 days, resulting in a mortality rate of 27.7%. There were significant differences between the survival group and the death group in age, ALT, Alb, ChE, MELD score, and incidence rates of hepatic encephalopathy, primary peritonitis, and hepatorenal syndrome (all P < 0.05). The logistic regression analysis showed that baseline hepatic encephalopathy (odds ratio [ OR ]=10.404, 95% confidence interval [ CI ]: 2.522-42.926, P =0.001), serum Alb at baseline ( OR =0.853, 95% CI : 0.764-0.952, P =0.005), and MELD score at baseline ( OR =1.143, 95% CI : 1.036-1.261, P =0.008) were independent predictive factors for the short-term prognosis of patients with HBV-related ACLF. A new predictive model was established based on the combination of these three indices, and the ROC curve analysis showed that this new model had an area under the curve of 0.833, while MELD score had an area under the ROC curve of 0.672. Conclusion As for the evaluation of the 90-day prognosis of patients with HBV-related ACLF, the new prognostic model established based on hepatic encephalopathy, Alb, and MELD score has a better predictive value than MELD score alone.