Objective:To summarize the characteristics of the participants (P), interventions (I), control measures (C), outcomes (O) and study design (S) of the clinical study of chronic back pain (CBP) in recent years; To further systematically organize the outcomes of the clinical study of CBP and their corresponding measurement tools.Methods:Clinical studies of CBP were retrieved from various databases including CNKI, Wanfang Database, VIP, SinoMed, Cochrane Library, Pubmed, Embase, Web of Science, etc. The search period was from January 1, 2015 to December 31, 2019. The retrieved literature was extracted and analyzed.The retrieved literatures will be extracted and analyzed. The retrieved literature was subjected to data extraction and analysis, and the quality of outcome indicators was evaluated according to 6 items. The Newcastle-Ottawa Scale ( NOS ) was used to evaluate the quality of cohort studies and case-control studies. Analyze the relationship between outcome indicators and interventions.Results:A total of 3 028 articles were finally included after examination and screening. The top 7 diagnoses of CBP were low back pain, lumbar disc protrusion, lumbar vertebral stenosis, lumbar vertebral slip, lumbar disc degression, non-specific chronic low back pain and post-operative pain syndrome. The top 7 intervention measures in clinical studies of CBP were surgery, acupuncture, physiotherapy, Tuina, exercise therapy, Western medicine painkillers and oral Chinese patent medicines. A total of 47 outcomes and 348 outcome measurement tools were reported in the literature included.Conclusion:In the clinical study of CBP in the recent years, there are problems such as incomplete and low quality of reporting, a wide variety of outcome measurement tools and lack of uniform reporting standards. The characteristics of patients determine the common characteristics of outcomes selection and it is also necessary to consider the specific outcomes related to interventions.

Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Objective　To investigate the correlation between serum uric acid and homocysteine levels in Parkinson’s disease (PD)，as well as the relationship between serum uric acid and homocysteine levels with cognitive impairment,clinical subtypes，different disease stages in PD.Methods　One hundred and fourteen patients with Parkinson’s disease and 123 healthy controls were included.Detailed baseline data were collected and patients with Parkinson’s disease were evaluated and grouped by Hoehn and Yahr、MDS-UPDRS and MMSE scale.Serum uric acid and homocysteine levels were measured and compared in all subjects.Results　The serum uric acid level of PD group was significantly lower than that of the control group［（241.2±60.8）μmol/L vs （271.2±55.7）μmol/L，P＜0.05］.The serum homocysteine level of PD group was significantly higher than that of the control group［（16.11±6.01）μmol/L vs (12.41±2.94) μmol/L，P＜0.05］.In PD group,serum uric acid level of patients with cognitive impairment was significantly lower than that of patients without cognitive impairment ［（22457.94）μmol/L vs （248.560.96）μmol/L，P＜0.05］,and there was no statistically significant difference between clinical subtypes and different disease stages in PD.Conclusion　Compared with the normal control group,serum uric acid level was significantly decreased in PD group,serum homocysteine level was significantly increased in PD group.In PD group,serum uric acid level was significantly lower in patients with cognitive impairment.

Objective:To detect the expression level of RAB39B gene and the effect of RAB39B on autophagy and α-synuclein, and then investigate the role of RAB39B gene mutation c.536dupA in the pathogenesis of Parkinson′s disease.Methods:Based on the novel RAB39B gene c.536 dupamutation identified in the previous work, the recombinant expression plasmid (pcDNA3.1-HA-RAB39B-536) of RAB39B gene with this mutation and wild-type recombinant expression plasmid (pcDNA3.1-HA-RAB39B) of RAB39B gene were constructed, and the recombinant expression plasmid was transfected into N2a cells with liposome as experimental group. The control group was made up with N2a cells transfected with plasmid pcDNA3.1-HA-RAB39B. Real-time polymerase chain reaction, Western blotting, immunofluorescence and immunoprecipitation techniques were used to detect the expression level of mutant RAB39B gene and the effects of RAB39B on autophagy and α-synuclein.Results:In the N2a cell model, the transcription level of mutant RAB39B was about twice that of wild type RAB39B, while the protein level of mutant RAB39B (0.30±0.00) was significantly lower than that of wild type (1.50±0.25, t=8.313, P<0.05). After adding proteasome inhibitor MG132, the protein level of mutant RAB39B increased (0.70±0.10, t=6.925, P<0.05); the level of microtubule-associated protein 1 light chain 3 BⅡ/Ⅰ of mutant RAB39B (3.11±0.30) was significantly lower than that of wild type (7.03±0.20, t=18.831, P<0.05); overexpression of wild type and mutant RAB39B did not affect the level of endogenous α-synuclein; overexpression of wild-type RAB39B resulted in elevated level of exogenous wild-type (p.A53T; from 0.60±0.11 to 1.25±0.08, t=8.254, P<0.05) and mutant (from 0.55±0.08 to 1.15±0.08, t=9.293, P<0.05) α-synuclein. Conclusions:The stability of the RAB39B protein decreased with the appearance of c.536 dupA mutation, the mutant protein may be degraded through the ubiquitin-proteasome pathway, and this mutation may affect the autophagy level of cells. RAB39B protein may interact with α-synuclein in vivo and may be involved in the maintenance of the stable level of α-synuclein.

Objective:To report the clinical, electrophysiological and genetic features in a Chinese family with distal hereditary motor neuropathy type V (dHMN-V) and screen the pathogenic mutant gene.Methods:A family with the history of inherited peripheral neuropathy was recruited in the First Affiliated Hospital of Zhengzhou University in July 2017. The clinical features and electrophysiological data were investigated. Genetic testing on well-established genes associated with hereditary peripheral neuropathy was conducted by targeted high throughput sequencing and the candidate variant was screened in the family and normal controls.Results:There were four affected individuals in the family. The proband, a 25-year-old male, was characterized by weakness and atrophy in the distal extremities primarily affected the upper extremities without sensory impairment. Electrophysiological study showed chronic neurogenic pattern in the upper and lower limb muscles. The motor conduction showed reduced velocity and compound muscle action potential amplitude, while the sensory conduction studies results were normal. The grandfather, a maternal uncle and a cousin of the proband exhibited similar clinical manifestations and electrophysiological abnormality. Genetic testing revealed a heterozygous mutation, c.880G>A(p.G294R), in the GARS gene in the proband. Proband′s mother and two other affected individuals carried the mutation which was confirmed by Sanger sequencing. The mutation site was not found in the unaffected members from the family and 300 unrelated normal controls. The variant is a novel mutation which has not been reported in dbSNP, ExAC and 1000 Genomes Project databases. Conclusion:The results suggest that the novel c.880G>A(p.G294R) mutation of the GARS gene is responsible for the Chinese patients with dHMN-V, and the findings broaden the mutational spectrum of GARS gene.

Objective To investigate correlation between the rs12122341 polymorphism and ischemic stroke and its major subtypes in Chinese Han population.Methods The patients with ischemic stroke and matched healthy controls in Chinese Han population were enrolled.The rs12122341 genotype was detected by the improved multiple ligase detection reaction (iMLDR).Results A total of 776 patients with ischemic stroke (415 large artery atherosclerotic stroke and 361 small artery occlusive stroke) and 776 healthy controls were enrolled.Genotyping showed that only rs12122341 CC and CG genotypes were detected in all subjects,and no GG genotype was detected.There was no significant difference in frequencies of allele and genotype between the patient group and the control group.Multivariate logistic regression analysis showed that there were no significant correlations between rs12122341 polymorphism and ischemic stroke (odds ratio [OR] 1.482,95％ confidence interval [CI]0.641-3.421;P =0.447),large artery atherosclerotic stroke (OR 1.972,95％ CI 0.655-6.034;P=0.227),and small arterial occlusive stroke (OR 1.632,95％ CI 0.437-6.262;P =1.000).Conclusions There is no significant correlation between the rs12122341 polymorphism and risk of ischemic stroke and its major subtypes in Chinese Han population.

Objective To analyze the clinical manifestations and genetic mutations in 3 pedigrees with hereditary spastic paraplegia (HSP).Methods Three pedigrees diagnosed as having HSP in our hospital from January 2014 to November 2015,were chosen;the clinical manifestations,electrophysiology and imaging features of the patients in these three families were analyzed.Genomic DNA was extracted from peripheral venous blood,and the targeted gene capturing was employed to identify the disease-causing genes of these patients.Results The patients from the first family was familiar HSP,and the main clinical features were progressive lower limbs weakness and abnormal gait without cognitive impairment;the patients from the second family were familiar HSP and those from the third family were HSP without family history,and the main clinical features of the two pedigrees were slowly progressive spastic paraplegia and cognitive impairment.In addition,thin corpus callosum was visible in MR imaging of family three.Genetic testing showed the first family presented with a known mutation c.715C＞T ofA TL1 exon 7 and the loci co-segregated in the family.The second family presented with novel compound heterozygous mutations in the SPG11 gene:c.3099_3103delGTTTG mutation of exon 17and c3817 3818insTGA mutation of exon 22;novel compound heterozygous mutations in the SPG11 gene in the third family were detected as follows:c.6194C ＞G mutation of exon 32 and c.5121+1C＞T splicing mutation ofintro 29.Conclusions Four novel mutations in SPG11 gene and one known mutation in A TL1 gene are found,which enriches the known HSP mutation types.Targeted gene capture is an efficient and rapid tool for identifying the causation of some complex and genetically heterogeneous neurodegenerative diseases.

Objective To look for more serum biomarkers supporting the diagnosis of multiple system atrophy ( MSA) and providing more evidence for early treatment.Methods All patients and healthy controls were enrolled from January 2011 to March 2015 in the First Affiliated Hospital of Zhengzhou University.Demographic features and biochemical examination results were collected.The t test was used to compare the lipid levels between MSA patients and controls.LSD-t test was used to compare the lipid levels among subtypes of MSA patients.Multivariate Logistic regression analysis was conducted to analyze the influencing factors.The relevance between lipid levels and onset age, disease duration and Hoehn & Yahr stage was calculated by Spearman correlation coefficients.Results Participants included 195 MSA patients and 195 age-and gender-matched controls with no neurological diseases.The levels of total cholesterol ((4.33 ±0.90) mmol/L), triglyceride ((1.27 ±0.71) mmol/L), low-density lipoprotein (LDL;(2.70 ±0.76) mmol/L) were significantly lower in patients than in controls ((4.52 ±0.85), (1.47 ± 0.86), (2.85 ±0.71) mmol/L ,t=2.056,2.528 and 2.149 respectively, all P<0.05).The levels of total cholesterol ((4.28 ±0.96) mmol/L) and triglyceride ((1.20 ±0.64) mmol/L) were significantly lower in MSA-P patients than in control group ((4.52 ±0.85), (1.47 ±0.86) mmol/L;LSD-t=1.983, 2.566, both P<0.05).After adjusting for age, gender and histories, the odds ratio ( OR) was 0.31 (95%CI 0.15-0.65, P =0.002 ) for MSA patients in the highest quartile of triglyceride and 0.38 (95%CI 0.17 -0.83,P=0.016) for those in the highest quartile of high-density lipoprotein (HDL), compared with the lowest quartiles.And HDL level was in a significantly positive correlation with onset age (r=0.15, P=0.039).Conclusion Our data suggest that triglyceride and HDL may be associated with the prevalence of MSA, and the lower levels of HDL, the earlier onset of MSA.

Objective To investigate the influence of one kind of defective gene NOTCH3 (R90C) of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in proliferation of oligodendrocyte lineage cells HS683 and their related molecular mechanism.Methods (1) A pCMV-Sport6.0 was chosen as the expression vector and site-directed mutation was used to construct the mutant NOTCH3 (p.R90C) expression vector;eukaryotic cell transfection technique was used to respectively transfect the pCMV-Sport6.0 empty vector,wild NOTCH3 vector (p.NOTCH3) and mutant NOTCH3 (p.R90C) expression vector to HS683 cells (blank control vector group,wild NOTCH3 vector group,and mutant NOTCH3 vector group);the protein expressions of NOTCH3,p53,phosphorylated p53 and p21 were detected by Westem blotting.(2) Wild NOTCH3 vector group,mutant NOTCH3 vector group and mutant NOTCH3 vector+pifithrin-α group were divided,and after wild NOTCH3 vector (p.NOTCH3) and mutant NOTCH3 (p.R90C) vector transfection,the latter two groups were added 0 or 1 μmol/L pifithrin-α,respectively;CCK-8 assay was employed to test the proliferation oftransfected HS683 cells 24,48 and 72,and 96 h after transfection.Results (1) As compared with wild NOTCH3 vector group,mutant NOTCH3 vector group had significantly lower absorbance value 24,48 and 72 h after transfection (P＜0.05);72 h after transfection,wild NOTCH3 vector group and mutant NOTCH3 vector group had significantly higher NOTCH3 protein expression as compared with blank control vector group (P＜0.05),and mutant NOTCH3 vector group had significantly higher p53,phosphorylated-p53 and p21 protein expressions as compared with wild NOTCH3 vector group and blank control vector group (P＜0.05).(2) The absorbance value in the mutant NOTCH3 vector+pifithrin-α group was significantly increased as compared with that in the mutant NOTCH3 vector group 48,72 and 96 h after transfection (P＜0.05).Conclusion Mutation of NOTCH3 (R90C) may inhibit the proliferation of oligodendrocyte cell lineage via p53 dependent way,which might play a direct role in demyelination pathology of CADASIL caused by NOTCH3(R90C).