Treatment of Syringomyelia Characterized by Focal Dilatation of the Central Canal Using Mesenchymal Stem Cells and Neural Stem Cells

BACKGROUND@#Syringomyelia is a progressive chronic disease that leads to nerve pain, sensory dissociation, and dyskinesia. Symptoms often do not improve after surgery. Stem cells have been widely explored for the treatment of nervous system diseases due to their immunoregulatory and neural replacement abilities. @*METHODS@#In this study, we used a rat model of syringomyelia characterized by focal dilatation of the central canal to explore an effective transplantation scheme and evaluate the effect of mesenchymal stem cells and induced neural stem cells for the treatment of syringomyelia. @*RESULTS@#The results showed that cell transplantation could not only promote syrinx shrinkage but also stimulate the proliferation of ependymal cells, and the effect of this result was related to the transplantation location. These reactions appeared only when the cells were transplanted into the cavity. Additionally, we discovered that cell transplantation transformed activated microglia into the M2 phenotype. IGF1-expressing M2 microglia may play a significant role in the repair of nerve pain. @*CONCLUSION@#Cell transplantation can promote cavity shrinkage and regulate the local inflammatory environment.Moreover, the proliferation of ependymal cells may indicate the activation of endogenous stem cells, which is important for the regeneration and repair of spinal cord injury.

GDF15 negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal squamous cell carcinoma / 医学前沿

Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.

Clinical features and laboratory characteristics of 4 cases of aromatic L-amino acid decarboxylase deficiency / 中华神经科杂志

Objective:To investigate the clinical characteristics, laboratory characteristics and genetic diagnosis of aromatic L-amino acid decarboxylase deficiency (AADCD), and to improve the understanding of this disease.Methods:Four children diagnosed with AADCD from the Department of Neurology, Beijing Children′s Hospital Affiliated to Capital Medical University from August 2016 to June 2020 were collected, and their clinical manifestations, laboratory and imaging data, and genetic test results were retrospectively analyzed.Results:All the 4 cases were diagnosed in early infancy, with the first symptom of feeding difficulties. They developed paroxysmal dyspraxia accompanied by eye movement crisis, movement regression, hypotonia, growth retardation, sleep disorders and autonomic nervous symptoms such as ptosis, excessive sweating and nasal congestion at the age of 2-4 months, respectively. The 4 children were siblings from 2 families with healthy parents. The dihydroxyphenylalanine decarboxylase ( DDC) gene mutations in cases 1 and 2 were derived from the maternal missense mutation c.1040G>A(P.RG347gln), and from the paternal deletion of exons 11 and 12, respectively. The DDC gene mutation in case 3 was derived from the maternal mutation c.419G>A(p.G140E) and the paternal mutation c.1375C>T(p.H459Y), respectively. Case 4 did not undergo genetic testing. Blood amino acid and acylcarnitine profiles and urine organic acid analyses were performed in 3 cases, and no specific abnormalities were found. In case 3, the results of 3-O-methyldopa (3-OMD) screening by blood dry filter paper increased significantly. Cerebrospinal fluid neurotransmitter detection results showed that the concentrations of 3-methoxy-4-hydroxyphenyldiol, vanillic acid and 5-hydroxyindoleacetic acid were significantly decreased, while the levels of 5-hydroxytryptophan and 3-OMD were increased in case 3. Blood aromatic L-amino acid decarboxylase (AADC) activity decreased significantly in case 3. Cranial magnetic resonance imaging (MRI) and electroencephalogram (EEG) examinations were performed in cases 1, 3, and 4, among which the cranial MRI in case 1 was normal, while the cranial MRI in cases 3 and 4 suggested that myelination was slightly backward. The EEG was normal in all the 3 cases. Cases 1 and 2 died of pneumonia and respiratory failure at the age of 1 year and 10 months. Case 3 was given clonazepam, benxel hydrochloride tablets and vitamin B6 tablets orally after diagnosis at the age of 4 months, and then treated with selegiline hydrochloride tablets and pramexol hydrochloride tablets. At the follow-up of 1 year and 6 months, the frequency of eye movement crisis and movement disorder was reduced, sleep was improved and autonomic nervous symptoms were alleviated, but there was no improvement in developmental delay. Case 4 was diagnosed with cerebral palsy and epilepsy, but failed various antiepileptic drugs and rehabilitation training, and died at the age of 10 due to heart failure and kidney failure. Conclusions:The clinical manifestations of AADCD are complicated and the misdiagnosis rate is high. Infants with early-onset hypotonia, developmental retardation, eye movement crisis, and movement disorders should be screened with dry filter paper as soon as possible for 3-OMD level, and suspicious cases should be diagnosed by cerebrospinal fluid neurotransmitter detection, plasma AADC activity determination, and gene examination. Early diagnosis of AADCD in children and gene mutation carriers can guide treatment and provide genetic counseling to reduce the incidence of the offspring.

Detection of BCR-ABL Fusion Gene in Chronic Myeloid Leukemia by Novel Digital PCR / 中国实验血液学杂志

OBJECTIVE@#To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABLp190/210/230.@*METHODS@#A new dPCR system for detecting BCR-ABLp190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared.@*RESULTS@#Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal.@*CONCLUSIONS@#This new dPCR detection system can be applied to the detection of BCR-ABLp190/210/230. It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.

Efficacy and safety of bosentan in the treatment of persistent pulmonary hypertension of the newborn: a Metaanalysis / 中国当代儿科杂志

OBJECTIVES@#To systematically evaluate the efficacy and safety of bosentan in the treatment of persistent pulmonary hypertension of the newborn (PPHN).@*METHODS@#Chinese Journal Full-text Database, Weipu Database, Wanfang Data, China Biology Medicine disc, PubMed, Web of Science, Embase, and Cochrane Library were searched for literature on bosentan in the treatment of PPHN published up to August 31, 2021.@*RESULTS@#A total of 8 randomized controlled trials were included for Meta analysis. The results of the Meta analysis showed that compared with the control group, the bosentan treatment group had a significantly lower treatment failure rate (RR=0.23, P<0.001), a significantly greater reduction in pulmonary artery pressure [mean difference (MD)=-11.79, P<0.001)], significantly greater increases in oxygen partial pressure (MD=10.21, P=0.006) and blood oxygen saturation (MD=8.30, P<0.001), and a significantly shorter length of hospital stay (MD=-1.35, P<0.001). The descriptive analysis showed that the bosentan treatment group had a lower degree of tricuspid regurgitation than the control group after treatment. The main adverse reactions of bosentan treatment included abnormal liver function, anemia and edema. The results of subgroup analysis based on treatment regimen, research area, and drug dose were consistent with those before stratification.@*CONCLUSIONS@#Bosentan is effective in the treatment of PPHN. However, when using bosentan, attention should be paid to adverse reactions such as abnormal liver function.

Effects of proton and heavy ion radiotherapy on nutritional status and adverse events in patients with malignant tumor / 中华临床营养杂志

Objective:To understand the effects of proton and heavy ion radiotherapy on nutritional status in patients with malignant tumors and to analyze the influencing factors of adverse events.Methods:Patients with malignant tumors who received proton and heavy ion therapy between October 2016 and September 2021were retrospectively included. The demographic characteristics, clinical diagnosis, radiotherapy regimen, nutritional indicators and adverse events were collected. Paired t test was used to analyze the changes in nutritional status before and after treatment and logistic regression was used to analyze the influencing factors of adverse events. Results:A total of 2,390 patients were enrolled and were stratified into 4 groups according to different radiotherapy regimen, namely proton, heavy ion, proton + heavy ion and photon + heavy ion radiotherapies. The prevalence of nutritional risk were 17.5% and 27.8% at admission and discharge, respectively. The prevalence of nutritional risk at discharge were 73.9% ( χ2 = 237.149, P < 0.01) in patients who received photon + heavy ion radiotherapy and 30.8% ( χ2 = 36.925, P < 0.01) in those who received proton + heavy ion radiotherapy. The prevalence of critical weight loss at discharge was 14.1%, with the absolute weight loss of 4.84 kg ( t = 11.716, P < 0.01) and 1.52 kg ( t = 29.530, P < 0.01) in photon + heavy ion radiotherapy and proton + heavy ion radiotherapy groups, respectively. All groups showed significant changes in serum albumin (ALB) and total lymphocyte count (TLC). Specifically, photon + heavy ion and proton + heavy ion therapy had a greater effect on serum ALB and TLC, with a decrease of 2.88 g/L and 2.18 g/L for ALB as well as a decrease of (1.06×10 9) /L and (0.80×10 9) /L for TLC ( P < 0.01). Multivariate logistic regression analysis showed that nutritional risk at admission and concurrent chemotherapy were independent factors for adverse events of proton and heavy ion radiotherapy ( OR = 1.404, 95% CI: 1.039 to 1.898; OR = 2.370, 95% CI: 1.781 to 3.154). Compared with heavy ion radiotherapy, the other 3 groups had more adverse events (proton, OR = 3.982, 95% CI: 2.533 to 6.259; proton + heavy ion, OR = 4.995, 95% CI: 3.688 to 6.766; photon + heavy ion, OR = 7.716, 95% CI: 5.079 to 11.720). Conclusions:Patients receiving proton and heavy ion therapy showed poorer nutritional status. Photon + heavy ion therapy had the greatest impact on nutritional status. Nutritional risk at admission and concurrent chemotherapy were independent factors for adverse events in patients receiving proton and heavy ion therapy.

Escore de Risco Clínico Simples para Prever a Mortalidade Pós-Alta Hospitalar em Pacientes Chineses Hospitalizados por Insuficiência Cardíaca / A Simple Clinical Risk Score to Predict Post-Discharge Mortality in Chinese Patients Hospitalized with Heart Failure

Resumo Fundamento Doenças cardiovasculares são a principal causa de morte na China. Entretanto, os esforços atuais para se identificar os fatores de risco de morte em pacientes hospitalizados com insuficiência cardíaca (IC) estão direcionados principalmente para a mortalidade durante a internação e a mortalidade após 30 dias nos Estados Unidos. Dessa forma, é necessário um modelo semelhante ao modelo utilizado para prever o risco considerado para procedimentos cirúrgicos cardiovasculares em pacientes para avaliar o risco de pacientes internados com diagnóstico de IC. Objetivo Identificar variáveis que podem prever a mortalidade por IC um ano após a alta hospitalar, e desenvolver um escore de risco para avaliar o risco de morte no período de um ano. Métodos No presente estudo, 1.742 pacientes chineses com IC foram divididos aleatoriamente em dois grupos: um grupo de amostra de derivação e um grupo de amostra de teste. O método de simulação Monte Carlo via Cadeias de Markov foi usado para identificar variáveis que podem prever a mortalidade um ano após a alta hospitalar. Variáveis com uma frequência >1% na análise bivariada, e que foram consideradas clinicamente significativas, foram qualificadas para análises de modelagens posteriores. A probabilidade posterior de que uma variável estava estatística e significativamente associada ao resultado foi calculada como o número total de vezes em que o IC de 95% da variável não coincidiu com 1 (ou seja, o ponto de referência), dividido pelo número total de iterações. Uma variável com uma probabilidade de 0,9 ou mais alta foi considerado um fator de risco robusto para prever o resultado, e foi incluída na lista final de variáveis. O nível de significância estatística adotado foi 5%. Resultados Cinco variáveis que pudessem prever de maneira robusta a mortalidade um ano após a alta hospitalar foram identificadas: idade, sexo feminino, escore da New York Heart Association (Associação de Cardiologia de Nova Iorque) >3, diâmetro do átrio esquerdo, e índice de massa corporal. Os modelos de derivação e de teste tiveram uma área de curva característica de operação do receptor de 0,79. Essas variáveis selecionadas foram utilizadas para avaliar o escore de risco de mortalidade por IC após um ano, e este foi dividido em três grupos (baixo, moderado e alto). O grupo de alto risco corresponde a aproximadamente 86% das mortes, e o grupo de risco moderado corresponde a 12% das mortes. Conclusão Um escore de risco de 5 variáveis simples pode ser utilizado para avaliar a mortalidade um ano após a alta hospitalar de pacientes internados com IC.

Abstract Background Cardiovascular diseases are the leading causes of death in China. However, present efforts to identify the risk factors for death in patients hospitalized with heart failure (HF) are primarily focused on in-hospital mortality and 30-day mortality in the United States. Thus, a model similar to the model used for predicting the risk in patients considered for cardiovascular surgical procedures is needed to evaluate the risk of the patients admitted with a diagnosis of HF. Objective To identify variables that can predict post-discharge one-year HF mortality and develop a risk score to assess the risk of dying within one year. Methods In the present study, 1,742 Chinese patients with HF were randomly divided into two groups: a derivation sample group and a test sample group. A Markov Chain Monte Carlo simulation method was used to identify variables that can predict the one-year post-discharge mortality. Variables with a frequency of >1% in the bivariate analysis and that were considered clinically meaningful were eligible for further modeling analyses. The posterior probability that a variable was statistically and significantly associated with the outcome was calculated as the total number of times that the variable's 95% CI did not overlap with 1 (i.e., the reference point) divided by the total number of iterations. A variable with a probability of 0.9 or higher was considered a robust risk factor for predicting the outcome, and this was included in the final variable list. The level of statistical significance adopted was 5%. Results Five variables that could robustly predict the one-year post-discharge mortality were identified: age, female gender, New York Heart Association functional classification score >3, left atrial diameter, and body mass index. Both derivation and test models had a receiver operating curve area of 0.79. These selected variables were used to assess the one-year HF mortality risk score, and these were divided into three groups (low, moderate, and high). The high-risk group corresponds to nearly 86% of the deaths, while the moderate group corresponds to 12% of the deaths. Conclusion A simple 5-variable risk score can be used to assess the one-year post-discharge mortality of hospitalized Chinese patients with HF.

Multicenter Randomized Controlled Clinical Trial of Longmu Zhuanggu Granule in Treatment of Children Recurrent Respiratory Infection with Lung-Spleen Qi Deficiency Syndrome / 中国实验方剂学杂志

Objective:To evaluate the clinical efficacy and safety of Longmu Zhuanggu granule for the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency. Method:This multicenter stratified， block-randomized， double-blind， double-dummy， positive drug （pidotimod granule） parallel controlled， and non-inferiority trail intended to included 240 children patients and divided them into the experimental group （<italic>n</italic>=120） and the control group （<italic>n</italic>=120） at the ratio of 1∶1. Patients in both groups were treated for eight successive weeks and followed up for 12 months. The cure rates， numbers of respiratory infections， average courses of disease， curative effects of traditional Chinese medicine （TCM） syndrome， curative effects of individual symptoms， curative effects of immune indexes， and safety indexes between the two groups were observed and compared. Result:A total of 237 subjects were collected from 10 research centers， including 119 cases in the control group and 118 in the experimental group. There were 236 cases enrolled into the full analysis set （FAS）， 210 into the per-protocol set （PPS）， and 236 into the safety set （SS）. The baseline data of the two groups were not significantly different from each other， indicating that they were comparable. The cure rates of the experimental group and control group were 75.21% （88/117） and 73.95%（88/119）， respectively， with the 95% confidence interval （CI） of difference between the two groups being 1.26% （-9.85%，12.37%） for FAS and 3.81% （-6.28%，13.90%） for PPS. The 95% CI fell within the 10% non-inferiority margin， implying that non-infertility test of the cure rate in the treatment of endpoint disease was valid， and the conclusions of FAS and PPS analysis were consistent. There was no significant difference in the number or course of upper respiratory infection， bronchitis， and pneumonia. The difference in curative effects of TCM syndrome between the two groups after four weeks of treatment was not remarkable. After eight weeks of treatment， the total effective rate of the experimental group was 84.62%（99/117）， statistically higher than 78.15%（93/119） of the control group（<italic>χ</italic>²=-3.26，<italic>P</italic><0.05）. There were no significant differences in the disappearance rates of individual symptoms between the two groups after four weeks of treatment. After eight weeks of treatment， the experimental group and control group exhibited the disappearance rates of 67.50%（54/80） and 47.37%（36/76） for shortness of breath and laziness to speak， 75.00%（54/72） and 53.33%（40/75） for poor appetite， 54.55%（60/110） and 37.84%（42/111） for hyperhidrosis， respectively， with obviously better outcomes observed in the experimental group （<italic>P</italic><0.05，<italic>P</italic><0.01）. The inter-group comparison revealed significant differences in immune indexes after eight weeks of treatment. As demonstrated by comparison with the situations before treatment， IgA， IgG， IgM， and CD4 did not change significantly after treatment. Except for CD8 in the experimental group (<italic>P</italic><0.05), there was no significant difference in other immune indexes before and after treatment There was no significant difference in the incidence of adverse reactions. Conclusion:Longmu Zhuanggu granule is not inferior to pidomod granule in the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency， and it exhibits good safety， implying its promising clinical application value.

Immune Mechanism of Tumor Cell Lysate Combined with IL-2 Preventing Melanoma and Inhibiting Tumor Growth / 肿瘤防治研究

Objective To investigate the preventive and inhibitory effects of tumor cell lysate(TCL) combined with IL-2 on melanoma and the potential immune mechanism. Methods The B16F10 melanoma TCL cell were prepared using an ultrasonic disruptor. Twenty-four C57BL/6 mice were randomly divided into four groups which were immunized with PBS, IL-2, TCL and TCL+IL-2 for three weeks, and contra lateral tumors were implanted in the fourth week. We observed onset time of tumor and tumor size, collected peripheral blood continuously and monitored the expression of CD4+T and CD8+T cell subsets dynamically by flow cytometry. Spleen and tumor tissues of mice were also tested for CD4+T and CD8+T cell subsets by flow cytometry and immunohistochemistry, respectively. Results The preventive immunization of the TCL+IL-2 group significantly delayed the onset time of tumor (P=0.034); moreover, the tumor volume (P=0.023) and tumor weight (P=0.0015) were also significantly smaller than those in the control group. The expression of CD8+T cell subsets in the TCL+IL-2 group and the TCL-only group were significantly higher than that in the control group (P=0.0016, P=0.012). However, the CD4+T cell subsets of the TCL+IL-2 group decreased after tumor implantation, compared with the control group (P=0.0089). The expression of CD4+T and CD8+T cell subsets in spleen and tumor tissues were as same as those in peripheral blood. Conclusion The tumor vaccine of TCL combined with IL-2 could prevent the occurrence of melanoma in mouse and effectively inhibit tumor growth by activating CD8+T cells.

Diffusion tensor imaging and resting-state functional magnetic resonance imaging in patients with delirium in intensive care unit / 中华危重病急救医学

Objective:To analyze the brain function of patients with delirium in intensive care unit (ICU) using resting-state functional magnetic resonance imaging (fMRI), further analyze the structural changes in the brain using diffusion tensor imaging (DTI), and explore the correlations of brain function with structural changes in patients with delirium in ICU from a new perspective of functional imaging, provide visual evidence for the diagnosis of delirium.Methods:Patients with delirium admitted to ICU of the Affiliated Hospital of Zunyi Medical University from January 1st to December 31st in 2017 were enrolled as subjects. During the same period, the healthy volunteers who matched the gender, age and education level of the patients with delirium were enrolled as control group. The intensive care delirium screening checklist (ICDSC) scores within 24 hours after ICU admission were recorded. All the subjects were scanned by fMRI and DTI. The abnormal changes in resting-state brain function of the patients with delirium were evaluated by cerebral regional homogeneity (ReHo) data analysis. The DTI data were processed by the FSL software, and the fractional anisotropy (FA) and mean diffusivity (MD) of the brain were extracted, respectively, to evaluate the damage to brain structure. The values of ReHo, FA and MD were compared between the two groups. The ReHo value of brain region with reduced ReHo value of patients with delirium as compared with the healthy volunteers was extracted for Pearson correlation analysis with ICDSC scores.Results:A total of 22 patients with delirium were included. Seven patients who did not cooperate in the examination, used sedatives or had false images in scanning, were excluded. Finally, 15 patients were enrolled in the delirium group, and 15 healthy volunteers in the healthy control group. ① No statistically significant difference was found in gender, age or education time between the two groups. ICDSC score of the delirium group was significantly higher than that of the healthy control group (6.07±1.28 vs. 1.07±0.88, P < 0.01). ② fMRI scanning and analysis results: compared with the healthy control group, the ReHo values of the cerebellum, right hippocampus, striatum, midbrain and pons in the delirium group were significantly increased (all P < 0.05, AlphaSim correction), while the ReHo values of bilateral superior frontal gyrus, bilateral median frontal gyrus, left inferior frontal gyrus, temporal lobe and parietal lobe were significantly lowered (all P < 0.05, AlphaSim correction). Correlation analysis showed that the ReHo value of the left superior frontal gyrus was negatively correlated with ICDSC score in the patients with delirium ( r = -0.794, P < 0.05), indicating that the changes in the functional area of the medial frontal gyrus was most closely related to delirium. ③ DTI scanning and analysis results: compared with the healthy control group, the FA values of the left cerebellum, bilateral frontal lobes, left temporal lobe, corpus callosum and left hippocampus in the delirium group were decreased significantly (all P < 0.05, AlphaSim correction), while the MD values of the medial frontal gyrus, right superior temporal gyrus, anterior cingulate gyrus, bilateral insular lobes and left caudate nucleus were enhanced significantly (all P < 0.05, AlphaSim correction), suggesting that the structural and functional damage was found in multiple brain regions in patients with delirium. Conclusions:Multiple brain regions of patients with delirium present abnormal resting-state brain function. The abnormal resting-state brain function of the left superior frontal gyrus is closely related to the occurrence of delirium. Structural damage is found in multiple brain regions of patients with delirium. The structural changes in the frontal lobe, temporal lobe, corpus callosum, hippocampus and cerebellum and their abnormal functions can be used as preliminary imaging indexes for the diagnosis of delirium.

Diagnostic value study of fractional exhaled nitric oxide (FeNO) in infants with recurrent wheezing / 国际儿科学杂志

Objective To analyze the correlation between the fractional exhaled nitric oxide (FeNO) levels and blood eosinophil (EOS) count and the frequency of wheeze in infants with recurrent wheezing.Methods From February 2015 to August 2016 in the General Hospital of Northern War Zone,outpatient department of Pediatrics treatment and hospitalization of age less than or equal to 3 year old children with recurrent wheezing,101 cases were induded as the research object.On the basis of asthma predictive index (API) score were divided into API positive group (n =55) and API negative group (n =46),according to the wheeze frequency of the two groups children were divided into 3 ～ 4 times wheezing groups and more than 5 times.Select 37 cases of healthy children as control group.The concentration of FeNO and blood EOS count are detected in all the children.The correlation between the three groups of children with FeNO concentration,the correlation between FeNO and blood EOS count,the correlation between the the frequency of wheeze and FeNO in experimental groups were analyzed.Results (1) API positive group mean FeNO (19.3 ± 6.2) ppb was significantly higher than API negative group (7.7 ± 2.9) ppb,there was no difference (P ＞ 0.05).API negative group mean FeNO (7.7 ± 2.9) ppb is lower than the normal control group (9.5 ± 2.0) ppb,there was no difference (P ＞0.05).(2) API positive group mean EOS count (124.7 ± 1.6) x 106/L is higher than API negative group (86.1 ± 1.9) x 106/L,there was significant difference (P ＜ 0.01);(3) There was a correlation between FeNO level and blood EOS count in API positive group,there was no correlation between FeNO level and blood EOS count in API negative group and con~ol group.(4) No statistical differences were found in ≤4 times wheezing groups and more than 5 times of the mean FeNO.Conclusion There is no significant difference in the mean value of FeNO between different times of wheezing in children with recurrent wheezing.The combination of medical history,EOS,FeNO and API might be used to predict the wheezing episode of infants.

Characteristic dysbiosis of gut microbiota of Chinese patients with diarrhea-predominant irritable bowel syndrome by an insight into the pan-microbiome / 中华医学杂志(英文版)

BACKGROUND@#Irritable bowel syndrome (IBS) is reported associated with the alteration of gut microbial composition termed as dysbiosis. However, the pathogenic mechanism of IBS remains unclear, while the studies of Chinese individuals are scarce. This study aimed to understand the concept of dysbiosis among patients with Chinese diarrhea-predominant IBS (IBS-D), as a degree of variance between the gut microbiomes of IBS-D population and that of a healthy population.@*METHODS@#The patients with IBS-D were recruited (assessed according to the Rome III criteria, by IBS symptom severity score) from the Outpatient Department of Gastroenterology of Peking University Third Hospital, and volunteers as healthy controls (HCs) were enrolled, during 2013. The 16S rRNA sequences were extracted from fecal samples. Ribosomal database project resources, basic local alignment search tool, and SparCC software were used to obtain the phylotype composition of samples and the internal interactions of the microbial community. Herein, the non-parametric test, Wilcoxon rank-sum test was carried out to find the statistical significance between HC and IBS-D groups. All the P values were adjusted to q values to decrease the error rate.@*RESULTS@#The study characterized the gut microbiomes of Chinese patients with IBS-D, and demonstrated that the dysbiosis could be characterized as directed alteration of the microbiome composition leading to greater disparity between relative abundance of two phyla, Bacteroidetes (Z = 4.77, q = 1.59 × 10) and Firmicutes (Z = -3.87, q = 5.83 × 10). Moreover, it indicated that the IBS symptom features were associated with the dysbiosis of whole gut microbiome, instead of one or several certain genera even they were dominating. Two genera, Bacteroides and Lachnospiracea incertae sedis, were identified as the core genera, meanwhile, the non-core genera contribute to a larger pan-microbiome of the gut microbiome. Furthermore, the dysbiosis in patients with IBS-D was associated with a reduction of network complexity of the interacted microbial community (HC vs. IBS-D: 639 vs. 154). The disordered metabolic functions of patients with IBS-D were identified as the potential influence of gut microbiome on the host (significant difference with q < 0.01 between HC and IBS-D).@*CONCLUSIONS@#This study supported the view of the potential influence of gut microbiome on the symptom of Chinese patients with IBS-D, and further characterized dysbiosis in Chinese patients with IBS-D, thus provided more pathological evidences for IBS-D with the further understanding of dysbiosis.

Increased Efficacy of Antivenom Combined with Hyperbaric Oxygen onEnvenomation in Adult Rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Snakebites are a neglected threat to global human health with a high morbidity rate. The present study explored the efficacy of antivenom with hyperbaric oxygen (HBO) intervention on snakebites, which could provide the experimental basis for clinical adjuvant therapy.</p><p><b>METHODS</b>Male Sprague-Dawley rats (n = 96) were randomized into four groups: the poison model was established by injecting Deinagkistrodon acutus (D. acutus) venom (0.8 LD50) via the caudal vein; the antivenom group was injected immediately with specific antivenom via the caudal vein after successful establishment of the envenomation model; and the antivenom + HBO group was exposed to HBO environment for 1 h once at predetermined periods of 0 h, 4 h, 12 h, and 23 h after antivenin administration. Each HBO time point had six rats; the control group was left untreated. The rats in the experimental group were euthanized at the corresponding time points after HBO therapy, and brain tissue and blood were harvested immediately. Hematoxylin and eosin (H&E) staining was used to investigate the pathological changes in the rat brain. Immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), and Western blotting were used to detect the expression of Nestin mRNA and protein in the subventricular zone (SVZ) of the brain. The levels of coagulation function (prothrombin time, activated partial thromboplastin time [APTT], and fibrinogen) and oxidation/antioxidation index (malondialdehyde [MDA] and superoxide dismutase [SOD]) were analyzed. Data were analyzed using one-way analysis of variance.</p><p><b>RESULTS</b>The brain tissue from rats in the poison model was observed for pathological changes using H&E staining. Tissues showed edema, decreased cell number, and disordered arrangement in the SVZ in the snake venom group. The antivenom - HBO intervention significantly alleviated these observations and was more prominent in the antivenom + HBO group. The serum levels of SOD and MDA in the snake venom group were increased and the antivenom - HBO intervention further increased the SOD levels but significantly decreased the MDA levels; however, this was enhanced within 1 h after HBO administration (MDA: F = 5.540, P = 0.008, SOD: F = 7.361, P = 0.000). Activated partial thromboplastin time (APTT) was significantly abnormal after venom administration but improved after antivenom and was even more significant in the antivenom + HBO group 5 h after envenomation (F = 25.430, P = 0.000). Only a few nestin-positive cells were observed in the envenomation model. The expression levels were significant in the antivenom and antivenom + HBO groups within 1 and 5 h after envenomation and were more significant in the antivenom + HBO group as determined by IHC, real-time PCR, and Western blotting (P < 0.05). D. acutus envenomation has neurotoxic effects in the brain of rats.</p><p><b>CONCLUSIONS</b>Antivenin and HBO, respectively, induced a neuroprotective effect after D. acutus envenomation by attenuating brain edema, upregulating nestin expression in SVZ, and improving coagulopathy and oxidative stress. The intervention efficacy of antivenom with HBO was maximum within 5 h after envenomation and was more efficacious than antivenom alone.</p>

Comparison of gut microbiotal compositional analysis of patients with irritable bowel syndrome through different bioinformatics pipelines / 北京大学学报(医学版)

OBJECTIVE@#To assess whether the same biological conclusion, diagnostic or curative effects regarding microbial composition of irritable bowel syndrome (IBS) patients could be reached through different bioinformatics pipelines, we used two common bioinformatics pipelines (Uparse V2.0 and Mothur V1.39.5)to analyze the same fecal microbial 16S rRNA high-throughput sequencing data.@*METHODS@#The two pipelines were used to analyze the diversity and richness of fecal microbial 16S rRNA high-throughput sequencing data of 27 samples, including 9 healthy controls (HC group), 9 diarrhea IBS patients before (IBS group) and after Rifaximin treatment (IBS-treatment, IBSt group). Analyses such as microbial diversity, principal co-ordinates analysis (PCoA), nonmetric multidimensional scaling (NMDS) and linear discriminant analysis effect size (LEfSe) were used to find out the microbial differences among HC group vs. IBS group and IBS group vs. IBSt group.@*RESULTS@#(1) Microbial composition comparison of the 27 samples in the two pipelines showed significant variations at both family and genera levels while no significant variations at phylum level; (2) There was no significant difference in the comparison of HC vs. IBS or IBS vs. IBSt (Uparse: HC vs. IBS, F=0.98, P=0.445; IBS vs. IBSt, F=0.47,P=0.926; Mothur: HC vs.IBS, F=0.82, P=0.646; IBS vs. IBSt, F=0.37, P=0.961). The Shannon index was significantly decreased in IBSt; (3) Both workshops distinguished the significantly enriched genera between HC and IBS groups. For example, Nitrosomonas and Paraprevotella increased while Pseudoalteromonadaceae and Anaerotruncus decreased in HC group through Uparse pipeline, nevertheless Roseburia 62 increased while Butyricicoccus and Moraxellaceae decreased in HC group through Mothur pipeline.Only Uparse pipeline could pick out significant genera between IBS and IBSt, such as Pseudobutyricibrio, Clostridiaceae 1 and Clostridiumsensustricto 1.@*CONCLUSION@#There were taxonomic and phylogenetic diversity differences between the two pipelines, Mothur can get more taxonomic details because the count number of each taxonomic level is higher. Both pipelines could distinguish the significantly enriched genera between HC and IBS groups, but Uparse was more capable to identity the difference between IBS and IBSt groups. To increase the reproducibility and reliability and to retain the consistency among similar studies, it is very important to consider the impact on different pipelines.

Soft corneal contact lens for postoperative comfort in patients with recurrent pterygium function / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To evaluate the effect of soft contact lens on the comfort of postoperative patients with recurrent pterygium. <p>METHODS: For 100 eyes of 98 patients after recurrent pterygium excision, the conjunctival implant with limbal stem cells from the upper part of the cornea was used, and the scleral surface of the operation area was transferred and covered. Fifty eyes were treated with corneal bandage lens for 5d(Group A)and 50 eyes were conventionally ensheathed(Group B). The time of corneal wound healing and various symptoms and signs were observed after operation. <p>RESULTS: Compared with Group B, 1d after pterygium, the symptoms and signs of corneal irritation in Group A were significantly less(<i>P</i><0.05), and the corneal epithelial healing was significantly faster and better(<i>P</i><0.05). <p>CONCLUSION: The corneal contact lens can obviously improve the early postoperative corneal irritation in patients with pterygium, promote corneal wound healing and relieve postoperative discomfort.

Study of renal protective effect of antivenom therapy assisted with hyperbaric oxygen in agkistrodon acutus poisoning rat / 重庆医学

Objective To investigate the renal protective effect of antivenom therapy assisted with hyperbaric oxygen(HBO) in agkistrodon acutus poisoning rat.Methods Ninety-six healthy adult male SpragueDawley rats were randomized into the control group(group A),snake venom poisoning group(group B),antivenom treatment group(group C) and antivenom+ HBO treatment group(group D),24 cases in each group.The group B,C and D were injected with agkistrodon acutus toxin 0.8 × LD50 (LD50 =1.594 mg/kg) by tail vein for establishing the poisoning model.The renal tissue pathological changes after agkistrodon acutus poisoning were observed.In the antivenom treatment group,antivenom(0.8 ×＜ 78 U/kg) was injected by tail vein after successfully constructing model,the group D was given once HBO treatment at 0,4,11 23 h after antivenom injection,while the group A was not given any treatment.Results The rats appeared obvious poisoning symptoms after snake venom intravenous injection.Compared with the group B,therat renal function and coagulation functions in the group C and D were significant improved,more over the group D was better than the group C(P＜0.05).The rats of the group B appeared glomerular hemorrhage,renal capsule expansion,different degrees of congestion in peripheral blood capillaries,renal tubular cavity dilation,cellular fatness,falling of brush border,vacuolation of renal tubular epithelial cells and inflammary cells infiltration in renal interstitial tissue.Along with time lapse,the renal hemorrhage was decreased and inflammatory cells infiltration was increased.The abovelesions in the group C and D were significantly improved.Conclusion The Agkistrodon acutus poisoning can lead to renal damage in rats;the antivenom treatment assisted with HBO has the protective effect on renal injury in agkistrodon acutus poisoning rat,moreover early adopting has better protective effect.

Effect of the serum ferritin, folic acid and its clinical efficacy by Chinese angelica astragalus decoction combined with iron sucrose injection in the treatment of the anemia patients with chronic renal failure / 中国生化药物杂志

Objective To investigate the effect of the serum ferritin,folic acid and its clinical efficacy by Chinese angelica Astragalus decoction combined with Iron Sucrose Injection in the treatment of the anemia patients with chronic renal failure.Methods 66 anemia patients with chronic renal failure were selected and randomly divided into the control group and the experiment group with 33 cases in each group.The control group were treated by Venofer and the experiment group were treated on the base of the control group with Chinese angelica and Astragalus Decoction.The clinical curative effect before and after treatment,serum ferritin,folic acid(SF),serum creatinine(Scr),urea nitrogen(BUN),creatinine clearance rate(Ccr),blood uric acid(UA),cholesterol(TC),total cholesterol(TG),high density lipoprotein(HDL-C)were compared after 6 months of treatment and the adverse reaction conditions was compared during the treatment between two groups.Results The effective rate of treatment in the control group was 69.70％lower than that in the observation group,the effective rate was 90.91％,with statistical significance(P<0.05).Compared with the control group,the SF and folic acid levels were lower,the Scr and BUN levels were lower,the Ccr and UA levels were higher,the TC and TG levelswere lower,the HDL-C level was higher,with statistical significance(P<0.05).Conclusion Angelica Astragalus decoction combined with Iron Sucrose Injection in the treatment of chronic renal failure patients with anemia effect is significant,can effectively reduce the level of serum ferritin and folic acid,the clinical effect is better.

Vector Construction,Protein Expression,Purification,and Identification of Calmodulin Mutants N2 and C2 / 中国医科大学学报

Objective To construct expression vectors of calmodulin(CaM)mutants N2 and C2,and to express,purify,and identify the mutant proteins,in order to study the interactions between CaM and calcium channels. Methods The cDNA of N?lobe and C?lobe of CaM were used to prepare the cDNA of N2 and C2. Next,the recombinant cDNAs were cloned into a pGEX?6p?3 plasmid,and the recombinant plasmids were trans?ferred into E.coli BL21 cells. The transfected BL21 cells were stimulated with IPTG. The fusion proteins were extracted by ultrasonication and puri?fied by using GS?4B beads. Finally,protein activity was identified by the pull?down assay. Results Both the restriction digestion map and the DNA sequence identification results confirmed that the recombinant plasmids were successfully constructed. SDS?PAGE results showed high purity and concentration of N2 and C2 proteins. Their activities and binding abilities with the calcium channel fragment were confirmed by the pull?down assay.Conclusion In this study,expression vectors of N2 and C2 are successfully constructed,and physiologically active N2 and C2 CaM mutant proteins are obtained.

Efficacy of half-dose verteporfin photodynamic therapy for central serous chorioretinophathy in patients aged above 45 / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the efficacy of half-dose verteporfin photodynamic therapy for central serous chorioretinophathy (CSC) in patients aged above 45 years old.METHODS:Thirty-two eyes of 30 patients aged above 45 years old with central serous chorioretinophathy were included,and all the eyes received half-dose verteporfin photodynamic therapy (PDT).Best-corrected visual acuity (BCVA),central macular thickness (CMT) and subretinal fluids absorption (SRF) were measured before and after treatment (1,3 and 6mo).RESULTS:The rate of SRF absorbing completely was 44％ at 1mo,63％ at 3mo and 75％ at 6mo.The difference in cure rate of the three time points was statistically significant (x2 =6.621,P=0.037).All the patients were divided into two groups according to the duration,patients in Group A were treated less than 6mo,Group B were ≥6mo.The mean LogMAR BCVA in the two groups were respectively 0.6149±0.4117 and 0.8167±0.4370 before treatment and the mean CMT were 409.47±129.422μ m and 395.82 ± 153.756μm before treatment.The difference between the two groups in the LogMAR BCVA was not statistically significant (F=0.303,P=0.823),but the time difference within the subjects was statistically significant (F=32.837,P＜ 0.001).In Group A,the differences of the LogMAR BCVA at pre-treatment,1 mo and 3mo was all statistically significant (P＜ 0.05),but the differences of the LogMAR BCVA at 3mo and 6mo was not statistically significant (t =2.024,P =0.063).In Group B,the differences of the LogMAR BCVA at any two time points were all statistically significant (P＜ 0.05).The difference between the two groups in the CMT was not statistically significant (F=0.064,P=0.978),but the time difference within the subjects was statistically significant (F=26.447,P＜0.001).In Group A,the differences of the CMT at any two time points were all statistically significant (P＜0.05).So were in Group B (P＜0.05).CONCLUSION:Half-dose verteporfin PDT was effective in treating CSC aged above 45 years old,it still could improve BCVA and subretinal fluids absorption.

Clinical features of unilateral oculomotor nerve palsy related to multiple myeloma:a case report and literature review / 中华全科医师杂志

Objective To analyze the clinical features of unilateral oculomotor nerve palsy caused by multiple myeloma(MM).Methods A 79-year-old female diagnosed MM for 3 years was admitted due to the disease relapse.The patient presented left oculomotor nerve palsy,bone marrow biopsy showed 4.5％ of myeloma cells,the serum level of λ light chain was up to 18 g/L,and brain CT/MRI scan revealed left parasphenoidsinus lesion.A diagnosis of relapsing intramedullary and extramedullary MM,IgGλ type,stage ⅢA was made.Ten cases were retrieved from literature since 1990,the clinical features of 11 cases were analyzed as follows.Results Among 11 cases of unilateral oculomotor nerve palsy caused by MM,7 were males and 4 females with a mean age of (60 ± 12) years (40-79 years).The sub-types of MM were IgG type (7 cases),IgA type (2 cases),biclonal of IgG and IgA type (1 case),and IgD type (1 case).Oculomotor nerve palsy was presented as the initial manifestation of MM in 9 cases,as a sign of relapse of MM in 1 case,and during MM treatment in 1 case.In 7 cases,oculomotor nerve was the only cranial nerve involved,while in other 4 cases,the Ⅳ,Ⅴ,Ⅵ cranial nerves were also involved.Neuroimaging revealed parasphenoid sinus lesions in 9 cases,and myeloma meningitis in 2 cases.Most of the reviewed cases achieved significant clinical improvement after chemotherapy and/or radiotherapy,except 2 cases with myeloma meningitis.The case in our department was improved significantly and rapidly after receiving chemotherapy with bortezomib.Conclusion MM should be considered when unilateral oculomotor nerve palsy is presented with or without the history of MM,the disease is sensitive to chemotherapy in most circumstances.