Molecular pathological mechanism of liver metabolic disorder in mice with severe spinal muscular atrophy / 南方医科大学学报

OBJECTIVE@#To explore the molecular pathological mechanism of liver metabolic disorder in severe spinal muscular atrophy (SMA).@*METHODS@#The transgenic mice with type Ⅰ SMA (Smn-/- SMN20tg/2tg) and littermate control mice (Smn+/- SMN20tg/2tg) were observed for milk suckling behavior and body weight changes after birth. The mice with type Ⅰ SMA mice were given an intraperitoneal injection of 20% glucose solution or saline (15 μL/12 h), and their survival time was recorded. GO enrichment analysis was performed using the RNA-Seq data of the liver of type Ⅰ SMA and littermate control mice, and the results were verified using quantitative real-time PCR. Bisulfite sequencing was performed to examine CpG island methylation level in Fasn gene promoter region in the liver of the neonatal mice.@*RESULTS@#The neonatal mice with type Ⅰ SMA showed normal milk suckling behavior but had lower body weight than the littermate control mice on the second day after birth. Intraperitoneal injection of glucose solution every 12 h significantly improved the median survival time of type Ⅰ SMA mice from 9±1.3 to 11± 1.5 days (P < 0.05). Analysis of the RNA-Seq data of the liver showed that the expression of the target genes of PPARα related to lipid metabolism and mitochondrial β oxidation were down-regulated in the liver of type Ⅰ SMA mice. Type Ⅰ SMA mice had higher methylation level of the Fasn promoter region in the liver than the littermate control mice (76.44% vs 58.67%). In primary cultures of hepatocytes from type Ⅰ SMA mice, treatment with 5-AzaC significantly up-regulated the expressions of the genes related to lipid metabolism by over 1 fold (P < 0.01).@*CONCLUSION@#Type Ⅰ SMA mice have liver metabolic disorder, and the down-regulation of the target genes of PPARα related to lipid and glucose metabolism due to persistent DNA methylation contributes to the progression of SMA.

RHD Gene Analysis of A Blood Donor with Del Phenotype / 中国实验血液学杂志

OBJECTIVE@#To analyze the RHD genotype of a blood donor with Del phenotype in Yunnan.@*METHODS@#Rh serological phenotype was identified. RHD gene was detected by PCR-SSP typing, and its 10 exons were sequenced. Exon 9 was amplified for sequencing and analysis. RHD zygosity was detected.@*RESULTS@#The Rh phenotype of this specimen was CcDelee. Genomic DNA exhibited a 1 003 bp deletion spanning from intron 8, across exon 9 into intron 9. The deletion breakpoints occurred between two 7-bp short tandem repeat sequences. There was no variation in the sequences of the remaining exons. The Rh hybridization box test showed that there was one RHD negative allele.@*CONCLUSION@#This specimen is Del type caused by deletion of RHD exon 9.

Effect of Naozhenning on Hippocampal Mitochondrial Function in Model Rats with Post-concussion Syndrome / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Naozhenning on learning and memory ability and neuron damage in hippocampal CA1 region of post-concussion syndrome model rats based on mitochondrial function. MethodMultiple cerebral concussion （MCC） was induced in SPF Wistar rats with the free-fall impact method. Then the model rats were randomly classified into model group （equivalent volume of distilled water）， piracetam （0.43 g·kg-1， ig） group， and low-， medium-， and high-dose NZN （5.4， 10.8， 21.6 g·kg-1， respectively， ig） groups， with 10 rats in each group， and another 10 normal rats were included in the normal control group （equivalent volume of distilled water）. The administration lasted 14 days and then relevant indexes were detected. Morris water maze test was used to observe the changes of learning and memory ability in each group， such as escape latency， residence time in primary quadrant， and times of crossing platform. The pathological changes of hippocampal CA1 region were observed based on hematoxylin-eosin （HE） staining and Nissl staining. The ultrastructure of mitochondria was observed under the transmission electron microscope （TME） and the activity of mitochondrial respiratory chain complex Ⅰ was detected by colorimetry. The content of adenosine triphosphate （ATP） was determined by fluorescence probe and mitochondrial membrane potential （MMP） by fluorescein enzyme-linked fluorescence immunoassay. ResultCompared with the normal control group， the model group showed long escape latency， short residence time in target quadrant， few times of crossing the platform， significant decrease in counts of neurons and Nissl bodies in hippocampal CA1 region， damage of neuronal morphology and mitochondrial structure， and significant reduction of MMP and the content of mitochondrial ATP and respiratory chain complex I （P<0.05， P<0.01）. The NZN groups demonstrated short escape latency， long residence time in target quadrant， increased times of crossing the platform， small number of neurons and Nissl bodies in hippocampal CA1 region， alleviated damage of neuronal morphology and mitochondrial structure， and increase in MMP and the content of mitochondrial ATP and respiratory chain complex I （P<0.05， P<0.01）. ConclusionNZN can improve the learning and memory ability of MCC rats by improving mitochondrial structure and function and alleviating hippocampal neuron injury.

Construction of a risk assessment indicator system for re-establishment of imported malaria / 中国血吸虫病防治杂志

Objective To create a risk assessment indicator system for re-establishment of imported malaria. Methods The risk assessment indicator system for re-establishment of imported malaria was preliminarily constructed through literature review and thematic discussions. A total of 26 malaria control experts were selected to carry out a two-round Delphi consultation of the indicator system. The active coefficient, authority coefficient and coordination coefficient of the experts and the coefficient of variation on each indicator were calculated for indicator screening and the weight of each indicator was calculated. The reliability of the indicator system was evaluated using Cronbach’s coefficient α, and the content validity of the indicator system was evaluated using the authority coefficient of the expert, while the structural validity of the indicator system was evaluated using Kaiser-Meyer-Olkin (KMO) test and factor analysis. Results Two rounds of Delphi expert consultations were completed by 23 malaria control experts, and a risk assessment indicator system for re-establishment of imported malaria was constructed, including 3 primary indicators, 7 secondary indicators, and 21 tertiary indicators. The active coefficient (100.00% vs. 88.46%; P < 0.01) and coordination coefficient of the expert (0.372 vs. 0.286; P < 0.01) were significantly greater in the second round of the Delphi expert consultation than in the first round. After the second round of the Delphi expert consultation, the authority coefficient of the experts ranged from 0.757 to 0.930 on each indicator, and the coefficients of variation were 0.098 to 0.136, 0.112 to 0.276 and 0.139 to 0.335 for the primary, secondary and tertiary indicators, respectively. The overall Cronbach’s coefficient α of the indicator system was 0.941, and there were significant differences in the KMO values for primary (KMO value = 0.523; χ2 = 18.192, P < 0.05), secondary (KMO value = 0.694, χ2 = 51.499, P < 0.01) and tertiary indicators (KMO value = 0.519; χ2 = 477.638, P < 0.01), while the cumulative contribution rate of six principal components in the tertiary indicators was 84.23%. The normalized weights of three primary indicators of the source of infection, transmission condition and control capability were 0.337, 0.333 and 0.329, and the three secondary indicators with the greatest normalized weights included the number of imported cases and malaria parasite species (0.160), introduction of imported cases in China and medical care seeking (0.152), vector species and density (0.152), while the five tertiary indicators with the greatest normalized weights included the malaria parasite species of imported cases (0.065), vector populations (0.064), and the time interval from onset to medical care seeking (0.059), number of imported cases (0.056), and the time interval from medical care seeking to definitive diagnosis (0.055). Conclusions A risk assessment indicator system for re-establishment of imported malaria is successfully created, which provides insights into the assessment of the risk of re-establishment of imported malaria and management of key high-risk factors in malaria-eliminated areas.

Repair of KuwadaⅡand Ⅲ Achilles tendon defects through modified medial J-shaped approach with autologous fascia lata transplantation / 中国骨伤

OBJECTIVE@#To investigate the clinical effect of modified medial J-shaped incision of Achilles tendon combined with fascia lata transplantation in the treatment of Kuwada typeⅡand Ⅲ Achilles tendon defects.@*METHODS@#From January 2016 to August 2018, the clinical data of 15 patients with KuwadaⅡand Ⅲ Achilles tendon defects treated with modified J-shaped approach with autologous fascia lata transplantation were retrospectively analyzed, including 14 males and 1 female, with an average age of 31.7 years old ranging from 24 to 43. There were 9 cases of KuwadaⅡdefect and 6 cases of KuwadaⅢ defect. Postoperative observations were made for incision complications, and the Arner-Lindholm scoring standard was used to evaluate the function of the affected foot at the last follow-up.@*RESULTS@#All 15 cases were followed up from 3 to 16 months with an average of 9.2 months. No skin necrosis or infection occurred after operation, and no Achilles tendon rupture occurred again. According to the Arner-Lindholm scoring standard, 13 cases were excellent, 2 cases were good.@*CONCLUSION@#Modified medial J-shaped incision is a satisfactory approach for repairing Achilles tendon defects. It is helpful to prevent postoperative incision complications, which double-strengthen the Achilles tendon strength, so that patients can perform early rehabilitation and functional exercises with satisfactory clinical results.

Application of lacosamide in sodium channel-related epilepsy in young infants / 中华神经科杂志

Objective:To report 2 young infants of sodium channel related epilepsy with SCN2A gene mutation, and to discuss the clinical characteristics of the disease and the efficacy and safety of lacosamide combined with the literature.Methods:Corresponding information of 2 children hospitalized in the Department of Neurology of Hunan Children′s Hospital in July 2021 and October 2021 was collected, including the symptoms, comprehensive physical examination, blood, cerebrospinal fluid, imaging, electrophysiological examination, diagnosis and treatment process, response to treatment and other clinical data, as well as the sequencing results of the whole exome of the children. The efficacy and safety of lacosamide were analyzed, and the related literatures of the Biomedical Literature Database, Wanfang Data Knowledge Service Platform and Chinese Knowledge Infrastructure Database were searched and reviewed.Results:Both of the 2 cases were girl. Their onset age was within 3 months. The initial symptoms were frequent convulsions and backward development. There was no structural abnormality in the head image. The convulsions could not be controlled according to conventional multidrug treatment. The seizures were quickly controlled with lacosamide. Now they have been followed up for 6 months. No obvious adverse reactions were found. Case 1 gene test results showed the SCN2A gene (chr2:166152333-166246334) heterozygous deletion, SCN1A gene (chr2:166847754-16693013) heterozygous deletion, the deletion size being about 5.72 Mb. Case 2 gene test results showed new missense mutation of SCN2A (c.1285G>A, p.Glu429Lys). There were dozens of seizures every day. They were treated with valproic acid, oxcarbazepine and levetiracetam successively. The seizures could not be controlled. Three focal seizures originated in the left temporal region were detected by electroencephalogram. There was no recurrence on the third day after adding lacosamide, and there was no attack after 5 months of follow-up. No obvious adverse reactions were found during follow-up.Conclusions:Sodium channel related epileptic encephalopathy often starts early, has frequent seizures, and can be accompanied by backward psychomotor development at the same time. The slow sodium channel blocker lacosamide has good efficacy and safety in the treatment of sodium channel-related epilepsy with SCN2A gene mutation or combined SCN1A gene mutation.

Glaucocalyxin A attenuates allergic responses by inhibiting mast cell degranulation through HMGB1/TLR4/NF-κB signaling pathways / 药学学报

The study is to investigate the effect of glaucocalyxin A (GLA) on mast cell-mediated anaphylaxis. The animal welfare and experimental process of this experiment followed the regulations of the Animal Ethics Committee of Yanbian University. BALB/c mice were used in the animal experiment and randomly divided into five groups, control group, model group, and GLA low, medium, and high dose groups (10, 20, and 40 mg·kg-1). Mice were sensitized by intradermal injection of anti-dinitrophenyl-immunoglobulin E (DNP-IgE) into the ears and challenged with a mixture of DNP-human serum albumin (HSA) and 4% evans blue into the tail veins to prepare an animal skin passive cutaneous anaphylaxis (PCA) model, which was collected from both ears for measurement of dye staining and histology. Rat peritoneal mast cells (RPMCs) were used in the cell experiment and divided into control, IgE + antigen (Ag), and IgE + Ag + GLA groups to determine histamine release as well as calcium influx levels. High-affinity IgE receptor (FcεRI)-mediated signaling pathway proteins and HMGB1/TLR4/NF-κB (high mobility group box 1/toll like receptor 4/nuclear transcription factor kappa B) signaling proteins were detected by Western blot. The results of animal experiments suggest that GLA inhibits PCA, reduces evans blue dye exudation, and reduces ear inflammation and ear thickness in mice. The results of cellular experiments suggested that GLA could reduce histamine release and calcium influx, and inhibit tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-13, and IL-1β production; Western blot results showed that GLA inhibited FcεRI-mediated phosphorylation levels of spleen tyrosine kinase (Syk), Lck/Yes novel tyrosine kinase (Lyn), tyrosine kinase Fyn (Fyn), growth-factor receptor-bound protein 2 (Gab2), and phospholipase C (PLC) γ1, while GLA inhibited HMGB1/TLR4 signaling pathway to limit NF-κB p65 nuclear metastasis. The results indicate that GLA inhibits mast cell degranulation and attenuates allergic inflammation through the HMGB1/TLR4/NF-κB signaling pathway.

Analysis of a child with carnitine palmitoyl transferase 1A deficiency due to variant of CPT1A gene / 中华医学遗传学杂志

OBJECTIVE@#To report on the clinical, metabolic and genetic characteristics of a child with carnitine palmitoyl transferase 1A (CPT1A) deficiency.@*METHODS@#Clinical data and the level of acylcarnitine for a child who initially presented as epilepsy were analyzed. Genomic DNA was extracted from peripheral blood samples of the child and her parents and subjected to next-generation sequencing (NGS).@*RESULTS@#Mass spectrometry of blood acylcarnitine indicated increased carnitine 0 (C0) and significantly increased C0/ (C16+C18). DNA sequencing revealed that the child has carried compound heterozygous variants of the CPT1A gene, namely c.1846G>A and c.2201T>C, which were respectively inherited from her mother and father.@*CONCLUSION@#CPT1A presenting initially as epilepsy was unreported previously. Analysis of blood acylcarnitine C0 and C0/ (C16 + C18) ratio and NGS are necessary for the identification and diagnosis of CPT1A deficiency. The c.1846G>A and c.2201T>C variants of the CPT1A gene probably underlay the disease in this child. Above finding has also enriched the spectrum of CPT1A gene variants.

Autophagy plays a protective role in advanced glycation end products- induced apoptosis of chondrocytes via regulation of tumor necrosis factor-α , nuclear factor-κ B and reactive oxygen species

Objective:To study the adverse effects of advanced glycation end products (AGEs) on chondrocytes and the role of autophagy in this process.Methods:Chondrocytes were harvested from the human articular cartilage tissues in surgery. AGEs were administered during chondrocytes culture. The rapamycin was used to induce autophagy. The cell viability was determined by 3-[4,5-dimethylthiazol2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. The expression of tumor necrosis factor- α (TNF- a ) and nuclear factor- κ B (NF- κ B) was detected by quantitative real-time polymerase chain reaction. The reactive oxygen species (ROS) production and apoptosis of the chondrocytes were determined by fluorescent probe and flow cytometer, respectively.Results:The chondrocytes viability was significantly reduced after 12 h incubation with AGEs (P<0.01)). In contrast, rapamycin pretreatment increased the chondrocytes viability through autophagy. AGEs increased TNF- α and NF- κ B mRNA expression of chondrocytes and autophagy receded or proceeded the change. AGEs increased intracellular ROS accumulation and autophagy reversed the change. AGEs accelerated chondrocytes apoptosis and autophagy suspended apoptosis.Conclusions:Accumulation of AGEs may have an adverse role for chondrocytes by increasing TNF- α and NF- κ B expression, ROS accumulation and apoptosis; meanwhile, autophagy ameliorates the AGEs- induced adverse effects.

Polydatin attenuates airway inflammation in asthmatic mouse model via p38 MAPK/Nrf2/HO-1 pathway / 中国药理学通报

Aim To investigate whether polydatin re-duces airway inflammation in asthmatic mouse model and explore whether this pathway is related to p38 MAPK/Nrf2/HO-1 . Methods After the establish-ment of the OVA-induced asthmatic mouse model, the animals were injected with 30 mg·kg-1 and 45 mg· kg-1 of polydatin diluted in 0. 2 mL normal saline, while the control group was replaced by normal saline. HE, PAS and Masson staining were used to observe the pathological changes of lung tissue. Diff-Quick staining was used to classify and count the number of inflamma-tory cells in BALF. ELISA was used to detect IgE ex-pressions in BALF. The content of ROS in BALF cells was detected by DHR-123 . The activities of antioxidant enzymes SOD, CAT and MDA in BALF were detected by the enzyme-linked immunosorbent assay kit. The expression of HO-1 in lung tissue was detected by im-munohistochemistry. The protein and mRNA expres-sions of Nrf2 and HO-1 in lung tissue of mice were de-tected by Western blot and RT-PCR. Results Poly-datin treatment significantly reduced inflammatory cell infiltration mucosal secretion, goblet cell proliferation and collagen deposition in the lung tissue of mice, and decreased the number of inflammatory cells and the ex-pression of total IgE and ROS in BALF. It also in-creased the levels of antioxidant enzymes such as SOD and CAT, and lowered the level of MDA. Polydatin re-duced the phosphorylation of p38 MAPK in the lung tissue of mice, enhanced the levels of mRNA and pro-tein expressions of Nrf2 and HO-1 and promoted the nuclear transfer of Nrf2 . The above effects of polydatin were dose-dependent. Conclusions Polydatin exerts anti-oxidative effects in OVA-induced asthmatic mouse model via anti-oxidant pathway. The mechanism may be achieved through the p38 MAPK/Nrf2/HO-1 path-way.

Epidemic status of human key parasitic diseases in Tongcheng City,Anhui Province / 中国血吸虫病防治杂志

Objective To understand the current status of key parasitic diseases in Tongcheng City,so as to provide an epi-demiological reference for formulating the scientific planning for "13thFive-year" parasitic diseases prevention and control. Methods The villages of different levels in Tongcheng City were sampled to investigate the infection of parasitic diseases of res-idents aged three or more years.Soil-transmitted nemathelminth,intestinal protozoa and Enterobius vermicularis were investigat-ed by the Kato-Katz technique(a fecal sample seized two),iodine smear method and cellophane tape method,respectively. Meanwhile a questionnaire survey was conducted on the basic situation,knowledge and health behaviors of the residents to soil-transmitted nemathelminth infection.Results Totally 1 023 residents were investigated,and 38 were positive of parasitic infec-tion,with the total infection rate of 3.71%.The soil-transmitted nematodes infection rate was 3.62%,36 people were infected with hookworm(3.52%),one person was infected with Trichuris trichiura(0.10%),one person was infected with intestinal pro-tozoa(Blastocystis hominis). Ascaris lumbricoides,E. vermicularis and tapeworm infections were not founded. The total aware-ness rate of prevention knowledge,behavior and attitude was 76.93%.Conclusions The infection rate of soil-transmitted nema-thelminth infections is reduced below 5% in Tongcheng City.The main species of parasites is Necator americanus,and the popu-lation of the infection is mainly concentrated in the residents over the age of 60 years.

Relationship Between Plasma Level of Neutrophil Gelatinase-associated lipocalin and Coronary Lesion Severity in Patients With Acute ST-elevation Myocardial Infarction / 中国循环杂志

Objective: To study the relationship between plasma levels of Neutrophil gelatinase- associated lipocalin (NGAL), matrix metalloproteinase (MMP-9), hs-CRP, IL-1β and the severity of coronary stenosis in acute ST-elevation myocardial infarction (STEMI) patients without kidney disease; to explore the ability for NGAL discriminating severe coronary stenosis. Methods: Our research included in 2 groups: STEMI group, n=124 patients admitted in our hospital from 2014-01 to 2017-03 and Control group, n=124 subjects without obvious coronary stenosis. According to SYNTAX score, the patients were divided into another set of 2 groups: High score group, patients with SYNTAX score ≥ 33, n=26 and Low score group, patients with SYNTAX score < 33, n = 98. Relationship between plasma levels of NGAL, MMP-9, hs-CRP, IL-1β and the severity of coronary stenosis were studied by Spearman correlation analysis; the ability for NGAL discriminating severe coronary stenosis was examined by ORC curve; the influencing factors for SYNTAX score were determined by Logistic regression analysis. Results: Compared with Control group, STEMI group had increased plasma levels of NGAL, MMP-9, hs-CRP, all P < 0.01,while IL-1β was similar between 2 groups, P=0.272. NGAL was positively related to MMP-9 (r=0.757, P<0.01), SYNTAX score (r=0.616, P<0.01) and IL-1β (r=0.185, P<0.05). Compared with Low score group, High score group showed the higher plasma levels of NGAL, MMP-9, both P<0.01, while the lower LVEF, P<0.01. The area under ROC curve for NGAL discriminating severe coronary stenosis was 0.881 (95% Cl 0.813-0.949, P<0.01) which was greater than MMP-9 [0.799 (95% Cl 0.709-0.890, P<0.01)] and hs-CRP [0.446 (95% Cl 0.306-0.587, P=0.400)]. Multivariate regression analysis presented that plasma NGAL level was independently related to high SYNTAX score [OR=1.115, 95% Cl (1.107-1.123), P<0.01]. Conclusion: STEMI patients had increased plasma levels of NGAL, MMP-9 and hs-CRP; NGAL had better ability for discriminating severe coronary stenosis than MMP-9 and hs-CRP. NGAL as a new biomarker should be helpful for risk stratification in STEMI patients.

Study on residents' satisfaction of basic public health services of urban and rural primary health care institutions / 中国卫生政策研究

Objective:To analyze the satisfaction degree and influencing factors of basic public health services in urban and rural areas in Hubei province,and to provide the evidence for further improvement of the quality of basic public health services. Methods:A total of 12 primary health institutions (6 urban community health service centers and 6 rural township hospitals) were selected from Wuhan,Huanggang,Jingzhou of Hubei Province. A questionnaire survey was conducted on the satisfaction,accessibility,comfort,safety and effectiveness of basic public health services among 719 residents. Results:The overall urban and rural residents'satisfaction score of basic public health service was 71.62 points,and the total satisfaction rate was 73.44%. The urban residents overall satisfaction score was 74.67 points,and the overall satisfaction rate was 75. 34%. The rural residents overall satisfaction score was 67.64 points,and the overall satisfaction rate was 71.52%. Among the specific indicators,the most satisfactory items were the convenience of visits (83.03%),privacy protection (80.25%),and indicators least satisfactory were medical technology(61.61%)and equipment facilities(64.53%). Logistics regression analy-sis showed that accessibility,comfort and safety of basic public health services had a greater impact on community residents' satisfaction;and gender and annual medical expenditure had a certain impact on residents'satisfaction. Conclusions:The over-all satisfaction of basic public health services in urban and rural residents of Hubei province is at a general level and still to be promoted. Urban residents'satisfaction is higher than that of the rural area. The basic public health services should further strengthen the quality improvement to further promote the equalization of basic public health services in rural as in urban areas.

Sesamin suppresses mast cell activation through inhibition of PKCα/NF-κB signaling pathway / 中国免疫学杂志

Objective:To investigate the effect of sesamin on mast cell activation and its inflammatory mediator release,as well as its possible mechanisms of action.Methods:HCM-1 cells were activation by stimulation with 10 μg/ml anti-DNP IgE for 6 h and challenge with 100 ng/ml DNP-HAS for 10 min.Sesamin was administration at the concentration of 25,50 and 100 μg/L prior to DNP-HAS challenge,subsequently the effect of sesamin on mast cell degranulation was investigated by light microscope,and histamine release and expression of cytokines such as TNF-α IL-6,IL-1β,IL-8 of mast cells after sesamin treatment were investigated by ELISA.Western blot was used to determine the effect of sesamin on FcεRI downstream signaling including Lyn,Syk and PKCα activation,and IκBα phosphorylation and NF-κB activation.Results:DNP-HAS significantly increased mast cell degranulation,histamine release and those cytokines expression,enhanced Lyn,Syk,PKCα,IκBα phosphorylation and NF-κB activation(P<0.05). Sesamin(50,100 μg/L) significantly decreased mast cell degranulation,histamine release and cytokines expression (TNF-α,IL-4,IL-1β,and IL-8),reduced activity of Lyn,Syk,kinases and PKCα and IκBα phosphorylation,and inhibited NF-κB activation(P<0.05).Conclusion: Sesamin suppresses mast cell activation and inflammatory mediators release through inhibition of PKCα/NF-κB signaling pathway.

Correlation between collateral circulation and cognitive impairment in patients with acute ischemic stroke / 国际脑血管病杂志

Objective To investigate the risk factors for cognitive impairment and their correlation with collateral circulation in patients with acute ischemic stroke.Methods From January 2016 to December 2017,patients with acute ischemic stroke admitted to the Department of Neurology,Jiangmen People's Hospital were enrolled.According to their status of collateral circulation,they were divided into either good collateral circulation group or poor collateral circulation group.According to the Montreal cognitive score,they were divided into cognitive impairment group and non-cognitive impairment group.Multivariate logistic regression analysis identified the independent risk factors for cognitive impairment in patients with acute ischemic stroke.Results A total of 225 patients were enrolled,including 106 females (47.1％) and 119 males (52.9％),aged 47-87 years,average 66.96 ± 9.65 years.The average baseline score of the National Institutes of Health Stroke Scale was 4.5 ± 2.1.Ninety-seven patients (43.1％) had cognitive impairment;79 had obvious stenosis or occlusion at the intracranial and extracranial segments of cerebral arteries;148 (65.8％) had good collateral circulation,and 77 (34.2％) had poor collateral circulation.The proportions of patients with atherosclerotic stroke (P =0.033) and cognitive impairment (P =0.041) in the good collateral circulation group were significantly higher than those in the poor collateral circulation group.There were significant differences in the proportions of patients with large-artery atherosclerotic stroke (P =0.007),anterior circulation stroke (P=0.018),collateral dysfunction (P=0.041),as well as baseline systolic blood pressure (P =0.006),baseline diastolic blood pressure (P =0.013),low-density lipoprotein cholesterol (P=0.021),and homocysteine (P=0.024) between the cognitive impairment group and the non-cognitive impairment group.Multivariate logistic regression analysis showed that baseline systolic blood pressure (odds ratio[OR] 1.007,95％ confidence interval[CI] 1.001-1.012;P =0.036),and large-artery atherosclerotic stroke (OR 2.650,95％ CI 1.490-4.714;P =0.001) were independently positively correlated with cognitive impairment,while the status of collateral circulation was not an independent risk factor for cognitive impairment (P =0.073).Conclusions The status of collateral circulation was associated with cognitive impairment in patients with acute ischemic stroke,but it was not an independent risk factor.

Influencing factors of serum complement C3 、C4 in children with myasthenia gravis / 国际儿科学杂志

Objective Complement plays an important role in the pathogenesis of myasthenia gravis.The formation of membrane attck complex and the damage of neuromuscular junction are inseparable from the activation of complement.Then to investigate the influencing factors of serum complement C3,C4 in children with myasthenia gravis and investigate the degree of influence of related factors.Methods One hundred sixty seven cases of hospitalized or outpatient myasthenia gravis children from the Department of Neurology in Hunan Children's Hospital were collected,including 33 cases of general MG,134 cases of ocular MG,and 36 cases of normal children as control group.The concentrations of serum C3,C4,IgG,IgM,IgA,IgE were detected by immune compare turbid.The influencing factors of complement C3,C4 were investigated and compared.Results The serum C3 levels were 1.07 ± 0.22 g/L,and the serum C4 levels were(0.17 ± 0.05)g/L in the general MG.The serum C3 levels were (1.01 ± 0.20)g/L,the serum C4 levels were(0.20 ± 0.08)g/L in the ocular MG.There were(1.36 ± 0.28) g/L for C3 levels,(0.25 ± 0.11) g/L for C4 levels in the control group.Compared with the control group,there were significant difference in C3 and C4 between the general MG and ocular MG(P ＜0.01 or 0.05).The partial correlations coefficients of C3 and course of disease,IgG and C3,C3 and C4 were-0.162,0.135,0.446(P ＜0.01 or 0.05).The multiple linear regression equations were as followed:C4 =0.420 × C3,C3 =0.655 + 1.148 × C4 + 0.008 × body weight-.005 × course of disease.Using univaruate analysis,the effect factors of C4(F =18.151,P =0.000),body weight(F =6.420,P =0.003),course of disease (F =3.015,P =0.039),age × course of disease × body weight (F =2.997,P =0.042) to C3 were significant (P ＜ 0.05,or P ＜ 0.01).Conclusion The C3 levels are mainly affected by C4,body weight,duration and some interaction effects among several impact factors in children with MG.C4 is mainly affected by C3.

The clinical efficacy and follow-up study of ketogenic diet adding treatment for refractor epilepsy in children / 中国医师杂志

Objective To study the clinical efficacy and follow-up study of ketogenic diet adding treatment for refractor epilepsy in children.Methods Cluster sampling method was employed to select children in children's hospital from January 2015 to June 2017,a total of 25 cases were diagnosed refractor epilepsy and adding ketogenic diet.Engel grade was used to evaluate the efficiency,the side effects,electroencephalogram (EEG) changes and intellectual development at 3 months,3-6 months,and more than 6 months.Results The effective rate of epileptic seizure control was 0,66.7％ and 87.5％ at 3 months,3 -6 months and ＞ 6 months respectively.The improvement rate of EEG discharge index was 33.3％,50％ and 81.3％ respectively.The improvement of intelligence development was 33.3％,50％ and 68.8％ respectively.Gastrointestinal disturbances were the main side effects.Severe side effect occurred in two cases--they had severe food refusal and were stopped the ketogenic diet adding treament.Conclusions The ketogenic diet is effective,safe,few side effects and tolerable in infants and children with refractory epilepsy.The ketogenic diet may improve cognition and behavior in addition to reducing seizure frequency,the interical epileptiform discharges (IED) index and improve the quality of life of epileptic children.However,the acceptance of ketogenic diet therapy for children is not satisfactory.The sample size is small and needs further promotion.While large samples and long-term observations are still desired to better recipes,and to provide possibly effective altemative to other therapies for refractor epilepsy.

Preparation of vincristine loaded low density lipoprotein nanoparticles modified by T7 peptide and evaluation of therapeutic effect on glioma / 药学学报

The purpose of this study was to prepare T7 peptide modified vincristine loaded low density lipoprotein (T7-LDL-VCR) nanoparticles to penetrate through blood brain barrier for targeting the brain tumor cells. Firstly, the low density lipoprotein (LDL) nanoparticles were extracted and separated from human serum by density gradient centrifugation method, and then was loaded into the nanoparticle's lipid core by the dry film method, T7 peptide was covalent modified on the surface of the nanoparticles. T7-LDL-VCR was characterized by particle size, entrapment efficiency and peptide attachment efficiency. The fluorescent probe DiR was used to track the brain biodistribution of T7-LDL-VCR in mice bearing intracranial C6 glioma by means of in vivo imaging. The therapeutic effect of nanoparticles was observed with magnetic resonance imaging (MRI). Finally, relative tumor volume and survival curve were determined in mice. The results showed that the mean size of the prepared T7-LDL-VCR nanoparticle was about 30 nm, encapsulation efficiency was 30.1%, and peptide attachment efficiency was 63.88%. As expected, the prepared preparation has good brain targeting and good effect on the treatment of glioma in mice:the relative tumor volumes of T7-VCR-LDL, LDL-VCR and VCR were 30%, 51.50% and 79.25%, respectively; the median survival time (36 days), which was 2, 1.85 and 1.38 fold higher than that of physiological saline, free VCR and LDL-VCR, respectively. This study suggests that dual modified hposomes possessed a better ability penetrating the blood brain barrier to target the brain tumor with significant antitumor activities.

Mechanism of Duhuo Jisheng decotion in delaying degeneration of nucleus pulposus cells in human intervertebral disc / 中国中药杂志

This paper aimed to investigate the role of Duhuo Jisheng decotion (DHJSD) in delaying human disc degeneration and its possible molecular mechanism. The intervertebral disc specimens were divided into normal and degenerated groups according to Pfirrmann classfication. The expressions of TNF-α, IL-1β, MMP-3 and MMP-13 in intervertebral disc tissue were detected by Western blot and PCR. Then degenerated human primary NPCs were cultured in vitro, the viability of NPCs treated with stromal cell-derived factor-1 (SDF-1，10 μg·L⁻¹)and various concentrations of DHJSD was assessed by the CCK-8 assay, and the appropriate concentration was screened. The experiment was divided into three groups, control group, SDF-1 group and DHJSD plus SDF-1 group. The levels of TNF-α, IL-1β, Agg, coIⅡ, MMP-3 and MMP-13 were detected. The levels of CXCR4, NF-κB major groups P65 phosphorylation (p-P65) and nuclear translocation, after treated with CXCR4 siRNA and NF-κB inhibitor (BAY11-7082) were measured by Western blot and immunofluorescence. At the same time, the expression of cell inflammatory factors and extracellular matrix were also measured. The expressions of TNF-α, IL-1β, MMP-3 and MMP-13 in the degenerated intervertebral disc tissue were significantly increased. In vitro study, the results of CCK-8 indicated that the viability of NPCs was significantly increased when DHJSD concentration was 300 mg·L⁻¹. After the experiment was divided into three groups, compared with SDF-1 group, the expressions of TNF-α, IL-1β, MMP-3 and MMP-13 in DHJSD group were significantly decreased, but the expressions of Agg, coIⅡ were significantly increased. When CXCR4-siRNA was transfected into NPCs, SDF-1 increased expressions of CXCR4 and p-P65 and inhibited nuclear translocation of P65, whose effect was suppressed by CXCR4-siRNA and DHJSD. In addition, when BAY11-7082 was used to treat NPCs, the expression of TNF-α, IL-1β, MMP-3 and MMP-13 were significantly decreased. DHJSD could inhibit the production of inflammatory factors and promote the synthesis of extracellular matrix. The potential mechanism may be related to the SDF-1/CXCR4/NF-κB signaling pathway.

Autophagy plays a protective role in advanced glycation end products-induced apoptosis of chondrocytes via regulation of tumor necrosis factor-

Objective: To study the adverse effects of advanced glycation end products (AGEs) on chondrocytes and the role of autophagy in this process. Methods: Chondrocytes were harvested from the human articular cartilage tissues in surgery. AGEs were administered during chondrocytes culture. The rapamycin was used to induce autophagy. The cell viability was determined by 3-[4,5-dimethylthiazol2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. The expression of tumor necrosis factor-? (TNF-?) and nuclear factor-?B (NF-?B) was detected by quantitative real-time polymerase chain reaction. The reactive oxygen species (ROS) production and apoptosis of the chondrocytes were determined by fluorescent probe and flow cytometer, respectively. Results: The chondrocytes viability was significantly reduced after 12 h incubation with AGEs (P<0.01)). In contrast, rapamycin pretreatment increased the chondrocytes viability through autophagy. AGEs increased TNF-? and NF-?B mRNA expression of chondrocytes and autophagy receded or proceeded the change. AGEs increased intracellular ROS accumulation and autophagy reversed the change. AGEs accelerated chondrocytes apoptosis and autophagy suspended apoptosis. Conclusions: Accumulation of AGEs may have an adverse role for chondrocytes by increasing TNF-? and NF-?B expression, ROS accumulation and apoptosis; meanwhile, autophagy ameliorates the AGEs-induced adverse effects.