Association of Polygenic Risk Score with Age at Onset and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease in a Chinese Cohort / 神经科学通报·英文版

To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer's disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aβ42, Aβ42/Aβ40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aβ42, Aβ42/Aβ40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.

Spicy food consumption is associated with cognition and cerebrospinal fluid biomarkers of Alzheimer disease / 中华医学杂志(英文版)

BACKGROUND@#Recent studies suggest that a healthy diet helps to prevent the development of Alzheimer disease (AD). This study aimed to investigate whether spicy food consumption is associated with cognition and cerebrospinal fluid (CSF) biomarkers of AD in the Chinese population.@*METHODS@#We enrolled 55 AD patients and 55 age- and gender-matched cognitively normal (CN) subjects in a case-control study, as well as a cohort of 131 participants without subjective cognitive decline (non-AD) in a cross-sectional study. Spicy food consumption was assessed using the Food Frequency Questionnaire (FFQ). Associations of FFQ scores with cognition and CSF biomarkers of AD were analyzed.@*RESULTS@#In the case-control study, spicy food consumption was lower in AD patients than that in CNs (4.0 [4.0-8.0] vs. 8.0 [4.5-10.0], P < 0.001); FFQ scores were positively associated with Mini-Mental Status Examination scores in the total sample (r = 0.218, P = 0.014). In the cross-sectional study, the association between spicy food consumption and cognition levels was verified in non-AD subjects (r = 0.264, P = 0.0023). Moreover, higher FFQ scores were significantly associated with higher β-Amyloid (1-42) (Aβ42) levels and lower phospho-tau/Aβ42 and total tau/Aβ42 ratios in the CSF of non-AD subjects (P < 0.05).@*CONCLUSION@#Spicy food consumption is closely related to higher cognition levels and reversed AD biomarkers in the CSF, suggesting that a capsaicin-rich diet might have the potential to modify the cognitive status and cerebral pathologies associated with AD.

A clinical study on leucogen tablets therapy efficacy during PEG-alpha interferon and alpha-interferon in chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To discuss the efficacy of Leucogen tablets treatment lessen the hematological reaction and raise the efficacy therapy of interferon in chronic hepatitis B treated with PEG-alpha interferon and alpha interferon.</p><p><b>METHODS</b>A total of 395 patients with HBeAg-positive chronic hepatitis B (CHB) inpatients from January 2002 to February 2011. Group: All the patients were assigned to A or B according as during the treatment added Leucogen tablets or not.</p><p><b>RESULTS</b>(1) All of 35.9% patients had neutrophil counts decrease under 1 x 10(9)/L, A group had 29.6%, B had 42.8% patients, P = 0.01; neutrophil counts < or = 0.75 x 10(9)/L A group had 12.6% ,B group had 26.4%, P = 0.02; neutrophil counts < or = 0. 5 x 10(9)/L A group had 4.8%, B group had 16.4%, P = 0.04. (2) A group had 8.2% patients interferon-alpha dose decreased, all the patient finished the period of therapy. B group had 23.3% patients interferon-alpha dose decreased, 2.1% of patients had paused. A group had 40.3% of patients interferon-alpha beyond conventional dose, B group had only 5.2%. (3) All of 9.8% patients had hematoblast decrease under 100 x 10(9)/L, A group had 8.7%, B had 11.1% patients; hematoblast < or = 80 x 10(9)/L A group had 5.3%, B group had 7.9%; hematoblast < or = 50 x 10(9)/L A group had 1.0%, B group had 2.6%. A group had the trend of reducing hematoblast decrease. (4) At the end of therapy A group had 67.4% patients HBVDNA < 100IU/ml, 54.3% e antigen negative, 40.7% e antigen conversed; B group had 53.9%, 41.2%, 26.9%, P was respectively 0.02, 0.01, 0.01.</p><p><b>CONCLUSION</b>Leucogen tablets treatment and prevention interferon-alpha-related neutrophil counts hematological reaction in CHB treated with alpha-interferon, and had the trend of reducing interferon-alpha-related hematoblast decrease, farther improved the efficacy of alpha-interferon treatment CHB.</p>

Efficacy and safety of ademetionine for treatment of drug-induced liver disease in children / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of ademetionine for treatment of cholestatic or mixed-type drug-induced liver disease (DILD) in children.</p><p><b>METHODS</b>The children with DILD were divided into the treated group and control group. Yinzhihuang Granule was orally administered and Compound Glycyrrhizin Injection intravenously given in patients of both groups. Those patients in the treated group were additionally treated with intravenous infusion of 250-1000 mg ademetionine for 28 d. The incidence of pruritus and adverse effects as well as biochemical parameters in all the patients and compared between the 2 groups. For statistical analysis, Chi2 test was used for between-group comparison and t test for processing the data.</p><p><b>RESULTS</b>1) Before treatment, severe pruritus was found in 17 and 16 children in the treated and control group, respectively. Two weeks after the treatment, the symptom was significantly relieved in 14 and 3 patients in the treated and control group, respectively (Chi2 = 4.52, P < 0.05). 2) As for comparisons between the 2 groups, a P value of 0.0014 for AST level was found 4 weeks, 0.045 and 0.007 for disappearance and recovery rate of jaundice, 0.0014 and 0.0006 for decrease in TBA level and 0.0003 for gammaGT level 2 and 4 weeks after the treatment.</p><p><b>CONCLUSION</b>Intravenous administration of ademetionine is safe in children with DILD and it can effectively alleviate pruritus, promote the recovery of various biochemical parameters and fasten liver functional recovery in these children. Therefore, ademetionine can be widely used for treatment of intrahepatic cholestasis in children.</p>

Clinical analysis of preoperative deep venous thrombosis (DVT) complicated lower extremity close fractures / 中国骨伤

<p><b>OBJECTIVE</b>To study the instance of deep venous thrombosis(DVT) complicated by preoperative lower extremity close fracture.</p><p><b>METHODS</b>Retrospectively analyzed the clinical data of 54 patients with DVT (through color Doppler to final diagnosis) complicated by preoperative lower extremity close fracture from March 2008 to February 2009, and explored the concomitant reason of DVT. There were 23 males and 31 females with age for 23-95 years old.</p><p><b>RESULTS</b>DVT including thrombus of ilio-venae external, thrombus of femoral vein, thrombus of popliteal vein, thrombus of posterior tibial veins and thrombus of soleus venae. The instance of DVT complicated by preoperative lower extremity close fracture: (1) The age of 23 cases (42.59%) more than 70 years. (2) 11 cases (20.37%) combined with syndrome, 2 cases had hypertension, 3 cases had hypertension and diabetes, 2 cases hypertension and cerbral infarction, 4 cases had hypertension, diabetes and coronary heart disease. (3) 10 cases (18.51%) were multi-fractures. (4) 28 cases (51.85%) occurred DVT at 7-14 days after lower extremity close fracture.</p><p><b>CONCLUSION</b>Advanced age, complicating hypertension, diabetes, coronary heart disease, cerbral infarction, multi-fractures may be lead to DVT. Multitudinous DVT occurred at 7-14 days after fracture, as early as possible operation has important significance on prevention DVT to decrease risk of pulmonary embolism.</p>

Effect of high-cholesterol diet on neuronal loss and Tau(ser202)phosphorylation in a rat model of Alzheimer's disease / 中华神经医学杂志

Objective To study the effect of high-cholesterol diet on neuronal loss and Tau (set202)phosphorylation in a rat model of Alzheimer's disease(AD). Methods Twenty rats were randomized into high-cholesterol diet+AD group,standard diet+AD group,high-cholesterol diet+PBS group,and standard diet+PBS group.In the former two groups,amyloid-β peptide(Aβ1-40)was injected into the right dentate gyms of the hippocampus to establish experimenml AD,and PBS was injected instead in the latter two groups.Corresponding feed was administered in the 4 groups aS indicated.The hippocampal neuronal loss in the rats Was assessed using Nissel staining,and the level of Tau(ser202)phosphorylation was estimated with immunohistochemistry.Result The mts in cholesterol+AD group exhibited serious neuronal loss at the rate of 30.9%±4.6%.which was significantly higher than those in standard diet+AD group(22.7%±1.9%),cholesterol+PBS group(7.0%±1.5%),and standard diet+PBS group(5.4%±1.1%).The numbers of Tau-positive cells in the dentate gyrus in the 4 groups were 65.5± 6.2,48.8±4.8,22.5±3.1,and 12.7±1.7,respectively. Conclusion High cholesterol diet aggravates neuronal loss and enhances Tan(ser202)phosphorylation in the dentate gyrus in AD rats.

Clinical value of protoparaxotril saporlirs combined with aspirin in the secondary prevention of cerebral infarction / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the clinical value of protoparaxotril saporlirs (PTS) combined with aspirin in the secondary prevention of cerebral infarction.</p><p><b>METHODS</b>The 140 patients with cerebral infarction were collected, among them the 120 patients during recovery stage were equally assigned to three groups by randomized, single blinded and open controlled principle, and they were treated respectively by PTS (A), aspirin (B), and PTS plus aspirin (C) for 6 months. The other 20, who couldn't or were unwilling to use aspirin, were arranged in group D for control. The platelet aggregation rate, incidence of stroke recurrence, gastrointestinal adverse reaction and the NIHSS scores of patients were observed during the six-month period of treatment.</p><p><b>RESULTS</b>As compared with group D, the lowering amplitude of platelet aggregation rate after treatment in the three treatment groups were significantly higher (P < 0.01). Comparison of platelet aggregation rate between group A and B showed significant difference after 3-month treatment (P < 0.05), but the difference became insignificant after 6-month treatment (P > 0.05). The incidence of stroke recurrence in the group A, B and C was 18.9%, 13.2% and 10.8% respectively, which showed no significant difference among them, but all were significantly lower than that in the group D (44.4%, P < 0.05). NIHSS scores in group A and C were significantly lower than in group B (P < 0.01); and the occurrence of gastrointestinal reaction was significantly lower in group A (P < 0.01).</p><p><b>CONCLUSION</b>Long-term application of PTS has the effects for preventing stroke recurrence, lowering gastrointestinal adverse reaction and improving patients' neural function in patients with stroke. As used in combination with aspirin, it shows potential practical importance in the clinical secondary prevention of stroke.</p>

Study on treatment effectiveness and safety in children with chronic hepatitis B or C using bicyclo tablets / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To evaluate treatment effectiveness and safety of bicyclo tablets in children with chronic hepatitis B or C.</p><p><b>METHODS</b>A randomized controlled trial was conducted in 148 children with chronic hepatitis B or C for evaluating safety, tolerability, and efficacy of treatment with bicyclo tablets or Hugan tablets. Children in therapy group were treated with bicyclo tablets and control group treated with Hugan tablets.</p><p><b>RESULTS</b>(1) ALT and AST level decreased more prominently in therapy group than in control group (P<0.01). (2) Bicyclo was more effective than Hugan tablets (P<0.01). (3) Symptoms were ameliorated more prominently in bicyclo group than in control group (P<0.01). (4) Both groups had no significant adverse events.</p><p><b>CONCLUSION</b>Satisfactory therapeutic effect and safety were obtained with bicyclo tablets in children with chronic hepatitis B or C.</p>

Analysis on prognostic factors of liver failure in children / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To analyze the prognostic factors of liver failure in children.</p><p><b>METHODS</b>The clinical data of 105 children with liver failure treated in the No. 302 Hospital in the past 17 years were retrospectively analyzed. The related factors were analysed by EXCELL 2000 and STATA 7.0, multivariate statistical analysis was performed by Logistic regression.</p><p><b>RESULTS</b>(1) A total of 72 children died and the mortality was 68.6%. (2) Univariate statistical analysis showed that the factors significantly correlated with death were age, clinical type and stage of liver failure, decrease in prothrombin activity (PTA) and albumin (AIB) level, increase in serum level of total bilirubin (TBIL), appearance of deviation of TBIL and ALT, complications and hepatic encephalopathy. There was no significant difference between boys and girls. (3) There was no significant difference among etiological diagnoses such as HBV infection, Wilson's disease, and unknown pathogeny. (4) Multivariate statistical analysis showed that PTA (P = 0.000) and TBIL (P = 0.029) were independent risk factors of mortality of the children.</p><p><b>CONCLUSION</b>The prognosis of liver failure in children is poor and mortality is high. PTA and TBIL might be useful for indicating prompt diagnosis and treatment to improve survival rate of the children with liver failure.</p>

An open-label pilot study evaluating the efficacy and safety of peginterferon alfa-2a combined with ribavirin in children with chronic hepatitis C / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of peginterferon alfa-2a plus ribavirin in the treatment of children with chronic hepatitis C (CHC) in China.</p><p><b>METHODS</b>Totally 54 children with CHC were treated with peginterferon alfa-2a plus ribavirin from July 2003 to July 2004. The dose of peginterferon alfa-2a was 104 microg.(m2)-1 per week. An inductive treatment with interferon 1-3 MIU q.o.d for a week was given before peginterferon for the reduction of possible side effects. Initially 1/3 to 1/2 dose of ribavirin was given and then the was gradually increased to an ideal level of 15-20 mg.kg(-1).d(-1).</p><p><b>RESULTS</b>The mean age of the patients was 11.3 years. Twenty three patients (42.6%) had received interferon plus ribavirin but the disease relapsed or did not respond to the treatment. The HCV of 70.8 percent of patients was genotype 1 and 14.8 percent of patients had a high viral load (>/=10(-6)/L). After 3-month treatment, 87.5% (42/48) and 8.3% (4/48) of the patients became HCV RNA negative or the viral load reduced by >/= 2 log, respectively, and only 8.3% (4/48) of the patients failed to respond. After 6-month treatment, 87.9% (29/33) and 6.1% (2/33) of the patients became HCV RNA negative or had a >/= 2 log reduction of HCV RNA, respectively, and only 6.1% (2/33) failed to respond. The adverse events were the typical of those reported in the treatment with interferon and ribavirin. Pyrexia occurred in 48.1% of patients, fatigue in 46.3%, decreased appetite in 9.3%, and skin rash in 3.7%. The absolute neutrophil counts of 51 patients (94.4%) were reduced to </= 2.0 x 10(-9)/L, and in 35.2% of them to < 1.0 x 10(-9)/L. Hemoglobin were reduced in only 2 patients (in one case to < 100 g/L, and in the other to < 110 g/L).</p><p><b>CONCLUSION</b>The regimen consisted of peginterferon alfa-2a and ribavirin achieved a high virologic response in Chinese children patients with chronic hepatitis C. No severe adverse events occurred and most of the patients well tolerated the treatment.</p>

Clinical features of liver failure in children / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To analyze the etiology, clinical and laboratory characteristics of hepatic failure in 105 children.</p><p><b>METHODS</b>The clinical data of 105 children with hepatic failure treated in our hospital from January 1986 to June 2003 were retrospectively analyzed by EXCELL 2000 and t test.</p><p><b>RESULTS</b>(1)Of the 105 children with hepatic failure, 9 were cases with fulminant hepatic failure, 38 with subacute hepatic failure and 58 with chronic hepatic failure. (2)Morbidity was the highest in 7-12 years old children (43/105, 41.0%) followed by infants (30/105, 28.6%). (3)CMV infection could be confirmed in 9 infants (30.0%), etiological diagnosis was not possible in 13 infants (43.3%). Etiological diagnosis could be confirmed in children over 1 year of age, which included hepatitis B (n=22, 29.3%), Wilson's disease (n=15, 20.0%), hepatitis A (n=10,13.3%). Etiology in 21 cases (28.0%) could not be confirmed. (4)Seventy-one cases (67.6%) had ascites, 34 of them (47.9%) had spontaneous peritonitis. Thirty-five cases were complicated with other infections. The commonest complication was pulmonary infection and sepsis was the next. Fifty-one cases (48.6%) had hydroelectrolyte imbalance. Forty-eight cases (46.2%) had hepatic encephalopathy, which may be subclinical in children under three years of age. (5)The incidence of hypoglycemia was 77.2%(71/92).</p><p><b>CONCLUSION</b>The etiology of liver failure was related to age. CMV infection was the commonest in infants. HBV, HAV infection was the commonest in children over 1 year of age and Wilson?s disease was the next. It is necessary to prevent and manage the associated complications as early as possible such as spontaneous peritonitis, hepatic encephalopathy, hydroelectrolyte imbalance and hypoglycemia etc.</p>

Association of T cell subsets with clinical status and hepatic pathology in children with chronic hepatitis B virus infection / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To study characteristics of peripheral T cell subsets in 94 children with chronic hepatitis B and to elucidate its relationships with clinical status and hepatic pathology.</p><p><b>METHODS</b>Peripheral T cell subsets were detected using flow cytometric analysis with specific monoclonal antibodies staining in 94 patients with HBV infection. The authors simultaneously detected their serum ALT, markers of HBV infection and examined liver biopsy material for pathological changes.</p><p><b>RESULTS</b>In patients with serious liver lesion, the ratio of CD4+/CD8+ cells was significantly higher than those with mild lesion (1.41+/-0.54 vs 1.08+/-0.35, P less than 0.05), which seemed to be associated with the various liver lesions among the patients. In female cases, the levels of CD4+ T cells and the ratio of CD4+/CD8+ T cells were higher than their counterpart in male cases (33.1+/-5.39 vs 28.8+/-6.28, 1.28+/-0.32 vs 1.02+/-0.36, P less than 0.05), but the level of CD8+ T cells was lower than those in males (26.79+/-4.66 vs 30.51+/-7.17, P less than 0.05). There was no obvious correlation between T cell subsets and circulating HBV viral load, the size of spleen among the HBV-infected children.</p><p><b>CONCLUSION</b>The characteristics of peripheral T cell subsets probably suggests the immune disorder occurred in these children with hepatitis B compared with healthy controls and its mechanism needs further investigation.</p>