Efficacy and safety of nerve growth factor for the treatment of neurological diseases:a meta-analysis of 64 randomized controlled trials involving 6,297 patients

OBJECTIVE： China is the only country where nerve growth factor is approved for large-scale use as a clinical medicine. More than 10 years ago, in 2003, nerve growth factor injection was listed as a national drug. The goal of this article is to evaluate comprehensively the efficacy and safety of nerve growth factor for the treatment of neurological diseases. DATA RETRIEVAL： A computer-based retrieval was performed from six databases, including the Cochrane Library, PubMed, EMBASE, Sino Med, CNKI, and the VIP database, searching from the clinical establishment of nerve growth factor for treatment until December 31, 2013. The key words for the searches were ＂nerve growth factor, randomized controlled trials＂ in Chinese and in English. DATA SELECTION： Inclusion criteria： any study published in English or Chinese referring to randomized controlled trials of nerve growth factor; patients with neurological diseases such as peripheral nerve injury, central nerve injury, cranial neuropathy, and nervous system infections; patients older than 7 years; similar research methods and outcomes assessing symptoms; and measurement of nerve conduction velocities. The meta-analysis was conducted using Review Manager 5.2.3 software. MAIN OUTCOME MEASURES： The total effective rate, the incidence of adverse effects, and the nerve conduction velocity were recorded for each study. RESULTS： Sixty-four studies involving 6,297 patients with neurological diseases were included. The total effective rate in the group treated with nerve growth factor was significantly higher than that in the control group （P 〈 0.0001, RR： 1.35, 95%CI： 1.30-1.40）. The average nerve conduction velocity in the nerve growth factor group was significantly higher than that in the control group （P 〈 0.00001, MD. 4.59 m/s, 95%CI： 4.12-5.06）. The incidence of pain or sclero- ma at the injection site in the nerve growth factor group was also higher than that in the control group （P 〈 0.00001, RR： 6.30, 95%CI： 3.53-11.27）, but such adverse effects were mild. CONCLUSION： Nerve growth factor can significantly improve nerve function in patients with nervous system disease and is safe and effective.

Ca2+/calmodulin-dependent protein kinase II regulates colon cancer proliferation and migration via ERK1/2 and p38 pathways

AIM To investigate the role of calmodulin-dependent protein kinase Ⅱ(Ca MKⅡ) in colon cancer growth,migration and invasion.METHODS Ca MKⅡ expression in colon cancer and paracancerous tissues was evaluated via immunochemistry. Transcriptional and posttranscriptional levels of Ca MKⅡin tissue samples and MMP2,MMP9 and TIMP-1 expression in the human colon cancer cell line HCT116 were assessed by q RTPCR and western blot. Cell proliferation was detected with the MTT assay. Cancer cell migration and invasion were investigated with the Transwell culture system and woundhealing assay.RESULTS We first demonstrated that CaMK Ⅱ was ove rexpressed in human colon cancers and was associated with cancer differentiation. In the human colon cancer cell line HCT116,the Ca MKII-specific inhibitor KN93,but not its inactive analogue KN92,decreased cancer cell proliferation. Furthermore,KN93 also significantly prohibited HCT116 cell migration and invasion. The specific inhibition of ERK1/2 or p38 decreased the proliferation and migration of colon cancer cells.CONCLUSION Our findings highlight Ca MKⅡ as a potential critical mediator in human colon tumor development and metastasis.

Coronaviruses and gastrointestinal diseases

The effects of coronaviruses on the respiratory system are of great concern,but their effects on the digestive system receive much less attention.Coronaviruses that infect mammals have shown gastrointestinal pathogenicity and caused symptoms such as diarrhea and vomiting.Available data have shown that human coronaviruses,including the newly emerged SARS-CoV-2,mainly infect the respiratory system and cause symptoms such as cough and fever,while they may generate gastrointestinal symptoms.However,there is little about the relation between coronavirus and digestive system.This review specifically addresses the effects of mammalian and human coronaviruses,including SARS-CoV-2,on the digestive tract,helping to cope with the new virus infection-induced disease,COVID-19.

Removing aluminum from a low-concentration lixivium of weathered crust elution-deposited rare earth ore with neutralizing hydrolysis

Aluminum,the main impurity in the lixivium of weathered crust elution deposited rare earth ore,not only results in an increasing consumption of precipitant in the rare earth precipitation process,but also lowers the purity of final rare earth product.Aluminum in the weathered crust elution-deposited rare earth ore lixivium should be removed.Neutralizing hydrolysis method was employed to remove aluminum from the lixivium.Hexamethylenetetramine was found to be the optimum pH regulator for the removal of aluminum in the low concentration.When used to adjust the pH value of the lixivium to 5.0,aluminum in the lixivium can be effectively removed in the form of aluminum hydroxide precipitation with removal rate of 97.60%.It shows that hexamethylenetetramine has a good effect on the removing of aluminum ions from the lowconcentration lixivium.Moreover,hexamethylenetetramine in removing aluminum from lixivium has little adverse effect on the RE precipitation process.

Posterior reversible encephalopathy syndrome in patients with hematologic tumor confers worse outcome

Background:This study aimed to evaluate the clinical features of posterior reversible encephalopathy syndrome(PRES)in children.Methods:The medical records of 31 patients from five medical centers who were diagnosed with PRES from 2001 to 2013 were retrospectively analyzed.In the 31 patients,16 were males,and 15 females,with a median age of 7 years(3-12 years).Patients younger than 10 years accounted for 74.2%of the 31 patients.Results:Seizure,the most common clinical sign,occurred in 29 of the 31 patients.Visual disturbances were also observed in 20 patients.Cerebral imaging abnormalities were bilateral and predominant in the parietal and occipital white matter.In this series,three patients died in the acute phase of PRES.One patient had resolution of neurologic presentation within one week,but no apparent improvement in radiological abnormalities was observed at eight months.One patient showed gradual recovery of both neurologic presentation and radiological abnormalities during follow-up at eight months.One patient developed long-term cortical blindness.All of the PRES patients with hematologic tumor had a worse prognosis than those without hematologic tumor.Conclusions:Seizure is a prevalent characteristic of children with PRES.Poor prognosis can be seen in PRES patients with hematologic tumor.

Integration of multiscale entropy and BASED scale of electroencephalography after adrenocorticotropic hormone therapy predict relapse of infantile spasms

Background Even though adrenocorticotropic hormone(ACTH)demonstrated powerful efficacy in the initially successful treatment of infantile spasms(IS),nearly half of patients have experienced a relapse.We sought to investigate whether features of electroencephalogram(EEG)predict relapse in those IS patients without structural brain abnormalities.Methods We retrospectively reviewed data from children with IS who achieved initial response after ACTH treatment,along with EEG recorded within the last two days of treatment.The recurrence of epileptic spasms following treatment was tracked for 12 months.Subjects were categorized as either non-relapse or relapse groups.General clinical and EEG recordings were collected,burden of amplitudes and epileptiform discharges(BASED)score and multiscale entropy(MSE)were carefully explored for cross-group comparisons.Results Forty-one patients were enrolled in the study,of which 26(63.4%)experienced a relapse.The BASED score was significantly higher in the relapse group.MSE in the non-relapse group was significantly lower than the relapse group in theγband but higher in the lower frequency range(δ,θ,α).Sensitivity and specificity were 85.71%and 92.31%,respectively,when combining MSE in theδ/γfrequency of the occipital region,plus BASED score were used to distinguish relapse from non-relapse groups.Conclusions BASED score and MSE of EEG after ACTH treatment could be used to predict relapse for IS patients without brain structural abnormalities.Patients with BASED score≥3,MSE increased in higher frequency,and decreased in lower frequency had a high risk of relapse.

Analysis of clinical characteristics of children with Aicardi-Goutieres syndrome in China

Background Aicardi-Goutieres syndrome(AGS)is an inflammatory disorder belonging to the type I interferonopathy group.The clinical diagnosis of AGS is difficult,which can lead to a high mortality rate.Overall,there is a lack of large-sample research data on AGS in China.We aim to summarize the clinical characteristics of Chinese patients with AGS and provide clues for clinical diagnostic.Methods The genetic and clinical features of Chinese patients with AGS were collected.Real-time polymerase chain reac-tion was used to detect expression of interferon-stimulated genes(ISGs).Results A total of 23 cases were included,consisting of 7 cases of AGS1 with three prime repair exonuclease 1 mutations,3 of AGS2 with ribonuclease H2 subunit B(RNASEH2B)mutations,3 of ASG3 with RNASEH2C,1 of AGS4 with RNASEH2A mutations,2 of AGS6 with adenosine deaminase acting on RNA 1 mutations,and 7 of AGS7 with interferon induced with helicase C domain 1 mutations.Onset before the age of 3 years occurred in 82.6%.Neurologic involvement was most common(100%),including signs of intracranial calcification which mainly distributed in the bilateral basal ganglia,leukodystrophy,dystonia,epilepsy,brain atrophy and dysphagia.Intellectual disability,language disability and motor skill impairment were also observed.Skin manifestations(60.87%)were dominated by a chilblain-like rash.Features such as microcephaly(47.62%),short stature(52.38%),liver dysfunction(42.11%),thyroid dysfunction(46.15%),positive autoimmune antibod-ies(66.67%),and elevated erythrocyte sedimentation rate(53.85%)were also found.The phenotypes of 2 cases fulfilled the diagnostic criteria for systemic lupus erythaematosus(SLE).One death was recorded.ISGs expression were elevated.Conclusions AGS is a systemic disease that causes sequelae and mortality.A diagnosis of AGS should be considered for patients who have an early onset of chilblain-like rash,intracranial calcification,leukodystrophy,dystonia,developmental delay,positive autoimmune antibodies,and elevated ISGs,and for those diagnosed with SLE with atypical presentation who are nonresponsive to conventional treatments.Comprehensive assessment of vital organ function and symptomatic treatment are important.