Objective To systematically assess the efficacy of memantine on moderate to severe Alzheimer's disease (AD).Methods With the evaluation method of the Cochrane system,searches were made in the Cochrane Library,MEDLINE,Embase,Forest Laboratories,CNKI,Wanfang Data,and VIP Data up to February 2013 for double blind,randomized,and placebo-controlled trials (RCTs) evaluating the efficacy of memantine for moderate to severe AD.A meta-analysis of included clinical trials was conducted using the Revman 5.2 software to evaluate the efficacy of memantine on overall clinical status,cognitive function activities of daily living,and behavioral and psychological disturbances.Results A total of 8 RCTs were included (2 527 patients with moderate to severe AD).Results of the meta-analysis showed that,for patients with moderate to severe AD,memantine had better efficacy than placebo on overall clinical status,cognitive function,and activities of daily living (MD=-0.24,95％CI:0.340.15;SMD=-0.26,95％CI:-0.340.18;SMD=-0.13,95％CI:-0.21-0.05),but there was no significant difference in efficacy on behavioral and psychological function between memantine and placebo (P =0.08).Analysis of subgroups showed that memantine had better efficacy than placebo on cognitive function in moderate AD patients (SMD =-0.22,95％CI:-0.37 0.06) and on overall clinical status,cognitive function,and activities of daily living in severe AD patients (MD-0.29,95％CI:-0.40 0.18;SMD=-0.31,95％CI:0.46-0.15;SMD=-0.16,95％ CI:-0.25 0.06;MD=-3.13,95％ CI:-4.88-1.39;respectively).Conclusions Memantine has efficacy on overall clinical status,cognitive function and activities of daily living in patients with moderate to severe AD,especially in patients with severe AD.

Aim To explore the possible protective effect of ginsenoside Rg1 on oligomeric Aβ1-42 induced apoptosis and its possible mechanism. Methods The damage was induced by oligomeric Aβ1-42 in primary cortical neurons. Cells were incubated in the absence or presence of Aβ, or co-incubated in sp600125 with Aβ, or pre-incubated in ginsenoside Rg1 then co-incu-bated in Aβ. The p-JNK, JNK, caspase-3 activity and TUNEL-positive cells were detected. Results In Aβ1-42 treated group, the ratio of p-JNK/JNK level was increased more than that in non-treated group for 15 min. However, in neurons preincubated with (2. 5, 5, 10 μmol·L-1 ) ginsenoside Rg1 and then co-incuba-ted with 5 μmol·L-1 oligomeric Aβ1-42 , the p-JNK/JNK ratio, caspase-3 activity and TUNEL positive neu-rons were significantly decreased compared with those of Aβ1-42 treated group. Conclusion Ginsenoside Rg1 can attenuate the oligomeric Aβ1-42-induced apop-tosis by JNK pathway.

Objective To investigate the possible effect of ginsenoside Rg1 and oligo Aβ1-42 on PKA/CREB pathway.Methods The damage was induced by oligomeric Aβ1-42 in primary cortical neuron.Neurons were incubated with or without glutamate,or incubated in Aβ,or pre-incubated in Rg1 and then co-incubated in Aβ.The proteins of p-CREB,t-CREB,PKA Ⅱ α and BDNF were detected by Western blot.Results After the treatment with Oligo Aβ1-42 for 2 h,the p-CREB/t-CREB level induced by glutamate was obviously lower (P＜ 0.001).However,in neurons pre incubatedwith 2.5,5.0,10.0 μmol/L of ginsenoside Rg1 and then co-incubated with 5μmol/L of oligo Aβ1-42,the p-CREB/t-CREB induced by glutamate was significantly increased as compared with that of Aβ1-42 group (P＜0.05).Upon Aβ1-42 exposure for 2 h,cortical neurons showed a statistically significant increase in PKA Ⅱ α as compared to the control group (P ＜ 0.001).Pre-treatmentwith varying doses of ginsenoside Rg1 (2.5,5,10μmol/L) showed a decrease in PKA Ⅱ α as compared to neurons treated with Aβ1-42 alone for 2 h (P＜0.001).Furthermore,BDNF level significantly increased in Rgl-pretreated cells as compared to cells treated with Aβ1-42 alone for 24h (P＜0.05).Conclusions Ginsenoside Rg1 attenuates the oligo Aβ142 inhibition of PKA/CREB pathway.

Objective To investigate the application value of fetal umbilical cord blood hemoglobin analysis in the prenatal diag ‐nosis of thalassemia .Methods 113 couples were the carriers of the same gene type of thalassemia ,moreover the females were in the pregnant period of 24 - 30 pregnant weeks and performed the prenatal diagnosis .The fetal umbilical cord blood hemoglobin compo‐nents were analyzed by the full automatic capillary electrophoresis technique ,meanwhile the fetal thalassemia gene was detected .Re‐sults Among 113 fetuses ,the umbilical cord blood HbBart′s level in 11 cases of severe α thalassemia was 85 .0% - 95 .5% ,which in 9 cases of intermediate type α thalassemia was 22 .0% - 39 .5% ;the umbilical cord blood HbA level in 6 cases of severe β thalas‐semia was 0% - 0 .4% ,which in 17 cases of light type β thalassemia was 2 .1% - 12 .5% .Conclusion The fetal umbilical cord blood hemoglobin analysis could be used for rapid prenatal diagnosis of severe α ,β and intermediate type α thalassemia ,which can serve as a supplementary method for the prenatal diagnosis of thalassemia .

Objective To detect the B cell epitopes of human MCHR1 recognized by serum autoantibodies in patients with vitiligo. Methods The DNA encoding antigen fragments of MCHR1 from amino acid (aa) 1 to 94 were amplified from pcDNA3/MCHR1 by PCR and inserted into the vector pGEX-4T-1. After identification, the recombinant plasmid pGEX-4T-1/MCHR1 was transfected into E. coli for fusion protein production which was purified by GST agarose affinity chromatography later. The sera from 38 vitiligo patients were examined for MCHR1 antibodies by enzyme-linked immunoabsorbent assay. Results Amino acids (aa) 1 to 94 of MCHR1 which most possibly included in B cell epitopes were selected to express. The recombinant plasmid pGEX-4T /MCHR1 was confirmed by sequence analysis. SDS-PAGE showed that a Mr 37 kD fusion protein was expressed by E.coli. Of the sera from vitiligo patients examined by ELISA, 5 of 38 were considered positive for MCHR1 antibody. Conclusion There are B cell epitopes in amino acids(aa) 1 to 94 of MCHR1 which can be recognized by antibodies from vitiligo patients.

Many pathogenic genes have been identified in early-onset Parkinson′s disease, but the early-onset Parkinson′s disease with 22q11.2 deletion has not been reported in Chinese. A case of early-onset Parkinson′s disease with 22q11.2 deletion was confirmed by whole-exome sequencing-based copy number variation detection in Fujian Medical University Union Hospital. This article reports its clinical characteristics and discusses its pathogenesis, diagnosis and treatment management.

Objective To discuss the clinical application of percutaneous radiologic gastrostomy (PRG) in treating dysphagia associated with amyotrophic lateral sclerosis (ALS),and to evaluate its safety and improvement effect on patient's nutritional status in ALS patients with pulmonary insufficiency.Methods The clinical data of 51 ALS patients who received PRG were retrospectively analyzed.The success rate of surgery and postoperative complications were recorded.All patients were regularly followed up,and the longterm complications as well as the one-,3-and 6-month mortality rates after the surgery were documented.The improvement of patient's nutritional status was evaluated.Results PRG was successfully accomplished in all 51 patients,the technical success rate was 100％.Mild postoperative complications occurred in 7 patients (13.73％) and severe massive hemorrhage in one patient (2.0％).After PRG,no signs or symptoms of impaired respiratory function were observed.No death occurred in one month and in 3 months after PRG.Six months after PRG,three patients died(6.8 ％,3/44).One month after PRG,31 patients had an increase in body weight of more than 1 kg,and the mean BMI was increased from preoperative t8.60±2.14 to postoperative 19.27±1.81 (one month after PRG),19.17±1.93 (3 month after PRG) and 18.89±2.33 (6 month after PRG).Conclusion For the performance of PRG no gastroscopy or anesthesia is needed,thus,the risk of aspiration asphyxia can be reduced in ALS patients complicated by pulmonary insufficiency and the success rate as well as the safety can be improved.Therefore,this technique is an effective means to ensure that the ALS patients with pulmonary insufficiency can get adequate energy intake to improve their nutritional status.

OBJECTIVETo assess the value of suspension array technology (SAT) for the genetic diagnosis of non-syndromic hearing loss (NSHL).

METHODSThree hundred and sixteen NSHL patients were simultaneously tested by SAT targeting 20 hotspot mutations within 4 common pathologic genes among the Chinese population as well as 9 deafness gene mutation detection kits. The results of the two approaches were validated by Sanger sequencing.

RESULTSAmong the 316 patients, 161 were found to carry a mutation by SAT. Sixty five patients have carried homozygous or compound heterozygous mutations, which yielded a mutation rate of 50.9% and a diagnostic rate of 21.2%. Seventy three patients were found to be carriers by the 9 deafness gene mutation detection kits. These included 34 patients carrying homozygous or compound heterozygous mutations, which yielded a mutation rate of 23.1% and diagnostic rate of 11.4%. Above results were consistent with those of Sanger sequencing.

CONCLUSIONSAT is a simple, rapid and accurate method featuring high detection rate for common mutations related to deafness among the Chinese population and has provided an effective means of genetic testing for hereditary deafness.

Objective:To construct a predictive model based on preoperative heat shock protein 90 alpha (HSP90 alpha) and lymphocyte count/monocyte ratio (LMR), for prediction of the textbook outcome (TO) of intrahepatic cholangiocarcinoma after surgery, and evaluate the predictive value of the model.Methods:Retrospective analysis of data from 210 patients with intrahepatic cholangiocarcinoma admitted to Chengde Central Hospital from January 2022 to December 2023, including 122 males and 88 females, aged (61.3±5.5) years. The patients were randomly divided into a training set (147 cases) and a validation set (63 cases) according to a ratio of 7: 3. According to whether the patients achieved TO after surgery, the patients in the training set were divided into a TO group ( n=39) and a non-TO group ( n=108). The conditions of tumor length < 5 cm, lymph node metastasis, large vessel invasion, preoperative HSP90α decrease, and preoperative LMR increase were compared between the two groups. Based on the training set, univariate and multivariate logistic regression were used to analyze the influencing factors of postoperative TO in patients with intrahepatic cholangiocarcinoma. Based on multi-factor results, R 4.3.0 software was used to construct a prediction model for TO. The model was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DSA). Results:Multivariate logistic regression analysis showed that the tumor diameter < 5 cm ( OR=1.917, 95% CI: 1.104-4.024), no lymph node metastasis ( OR=2.489, 95% CI: 1.030-3.619), and no invasion of large vessels ( OR=2.565, 95% CI: 2.097-5.093), the decrease of HSP90α before surgery ( OR=3.161, 95% CI: 2.536-5.358), and the increase of LMR before surgery ( OR=2.088, 95% CI: 1.454-4.262) were the influencing factors for patients TO achieve postoperative TO (all P<0.05). A correlation nomogram model was built based on the above indicators. The area under the curve of the model predicting the postoperative TO of the patients in the training set and the test set were 0.875 (95% CI: 0.782-0.938) and 0.860 (95% CI: 0.767-0.912), respectively, indicating good predictive value of the model. The calibration curve was basically consistent with the standard curve, indicating that the model has good consistency and accuracy. DCA results showed that the models had good clinical net benefit in the threshold probability range of 0.1~0.8. Conclusion:The nomogram model based on perioperative HSP90α and LMR has good accuracy and clinical applicability in predicting the possibility of achieving TO after surgery for cholangiocarcinoma, which can provide a reference for clinical treatment.

Objective To study the clinical features and risk factors of acute pulmonary reperfusion injury after operation in neonates with severe pulmonary stenosis or pulmonary atresia.Method From February 2014 to February 2018,a retrospective analysis was performed in patients with critical pulmonary stenosis or pulmonary atresia who received percutaneous balloon pulmonary valvuloplasty (PBPV) in the neonatal intensive care unit of our hospital.Clinical characteristics,perioperative cardiac structure,hemodynamic data and biochemical results were collected.The neonates were assigned into injury group if they had acute lung reperfusion injury,and non-injury group if not.The risk factors of acute lung reperfusion injury were analyzed using multi-variate Logistic regression model.Result A total of 32 patients (24 prenatal diagnosis and 8 postnatal diagnosis) with severe pulmonary stenosis or pulmonary atresia with intact ventricular septum were enrolled.The main manifestations were dyspnea and cyanosis.Intravenous prostaglandin E was administered to keep the ductus arteriosus open.The age of operation ranged from 1 to 52 days and the median age was 7.5 days.Postoperative acute lung reperfusion injury occurred in 7 cases (21.9％).Preoperative and intraoperative pulmonary valve annulus diameter,balloon diameter,preoperative hemoglobin,hematocrit and blood albumin were significantly lower in the injury group.The operation duration,total length of hospital stay and postoperative duration were longer than in the non-injury group,the differences were statistically significant (P ＜ 0.05).Multi-variate Logistic regression analysis showed that the diameter of pulmonary valve annulus (OR =5.814,95％CI 1.106 ～30.568),preoperative blood albumin (OR =1.361,95％ CI 1.063 ～ 1.742),and hematocrit (OR =1.173,95％ CI 1.010 ～ 1.363) were risk factors of acute lung reperfusion injury,with statistically significant differences (P ＜ 0.05).Conclusion Acute lung reperfusion injury is one of the common complications after the operation of severe pulmonary stenosis or pulmonary atresia.The severity of pulmonary valve annulus stenosis,preoperative hematocrit and blood albumin level may be the risk factors of postoperative acute lung reperfusion injury.