Objective To investigate the effects of astragaloside Ⅳ(AS-Ⅳ)on axon growth inhibitory factor A(Nogo-A)and its downstream pathway protein RHO-associated coiled spiral kinase 2(ROCK2)in experimental autoimmune encephalomyelitis(EAE)mice,and to explore the mechanism by which it promotes axon repair and regeneration.Methods EAE model was induced in C57BL/6 female mice by subcutaneous injection of myelin oligodendrocyte glycoprotein 35-55(MOG35-55).Mice were randomly divided into EAE group and AS-Ⅳ group(n=8 per group).EAE group received intraperitoneal injection of PBS on the 3rd day post-immunization,while AS-Ⅳ group was administered AS-Ⅳ at a dosage of 30mg/(kg.d)once daily,0.2 ml per injection,for 25 consecutive days.On the 28th day post-immunization,the expression levels of growth-associated protein 43(GAP-43),neuronal core antigen(NeuN),microtubule associated protein 2(MAP-2),glial fibroacidic protein(GFAP),and Iba1 in the spinal cord were detected using immunofluorescence assay.Real-time fluorescence quantitative PCR(qRT-PCR)was conducted to detect mRNA expression levels of GAP-43,Nogo-A,and Nogo receptor(NgR)genes.Western blotting was utilized to determine the expression levels of GAP-43,Nogo-A,ROCK2,phosphorylated myosin phosphatase(p-MYPT1),B-lymphoblastoma-2(Bcl-2),and Bcl-2 associated X protein(Bax).Results Compared with EAE group,AS-Ⅳ treatment significantly reduced the positive cell expression rates of Iba1 microglia and GFAP astrocyte in spinal cord(P<0.01 and P<0.001,respectively),while it also increased the positive expression rates of NeuN and MAP-2(P<0.001 and P<0.05,respectively).The treatment also upregulated the expression level of anti-apoptotic factor Bcl-2(P<0.001)and downregulated the expression level of pro-apoptotic factor Bax(P<0.05),leading to an increase in Bcl-2/Bax ratio(P<0.05).Furthermore,AS-Ⅳ enhanced the expression of GAP-43 protein(P<0.05)and decreased the mRNA expression levels of neuroregeneration inhibitor Nogo receptor(NgR)and ROCK2 gene(P<0.001,P<0.05,respectively);as well as decreased the expression levels of Nogo-A,ROCK2 and p-MYPT1 proteins(P<0.05,P<0.001).Conclusion AS-Ⅳ may inhibit the activation of microglia and astrocytes and neuronal apoptosis in EAE mice by inhibiting Nogo-A and downstream pathway ROCK 2,thereby promoting the expression of GAP-43,NeuN and MAP-2,alleviating neuronal damage,and facilitating axon repair and regeneration.

ObjectivesBased on the changes of lung lesions in patients with COVID-19 at different stages， a nomogram model describing CT image features was established by radiomics method to explore its efficacy in predicting the progression of the disease. MethodsThis retrospective study enrolled 136 patients with COVID-19 pneumonia who received at least two CTs including three cohorts （training cohort and validation cohort 1 and 2）. Patients in the training cohort were divided into three groups according to time between onset of fever symptoms and the first CT. The clinical manifestations and CT features of each group were analyzed and compared. A nomogram to predict disease progression was constructed according to the CT features of the patients， and its performance was evaluated. ResultsThe training cohort consisted of 41 patients.A nomogram was generated to predict disease progression based on three CT features： irregular strip shadow， air bronchial sign， and the proportion of lesions with irregular shape ≥50%. AUC（95%CI）=0.906（0.817，0.995）.The C index of the training cohort was 0.906， and the C index of the internal verification was 0.892. AUC（95%CI）of the validation cohort 1 （34 cases） =0.889（0.793，0.984）；AUC（95%CI）of the validation cohort 2 （61 cases）=0.876（0.706，1.000）.The calibration curves show that the predicted values of the nomogram are in good agreement with the observed values. ConclusionThe nomogram model based on CT radiomics can predict the outcome of lung lesions in patients with high sensitivity and specificity.According to the changes of CT image characteristics of patients with COVID-19， lung lesions will be improved when the proportion of irregular cable shadow， air bronchogram and irregular lesions is greater than 50%.

The UHPLC-LTQ-orbitrap-MS metabolomics technique was used to determine the effect of deapio-platycodin D (DPD) on endogenous metabolites in lung tissues of mice with ammonia-induced cough, and to identify the metabolic regulatory pathways of DPD in its antitussive and expectorant activities. This work was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (Approval No. JZLLSC-20190235). Metabolites were identified by UHPLC-LTQ-orbitrap-MS method and the metabolic pathways related to differentially-expressed metabolites were analyzed by the MetaboAnalyst platform. DPD significantly prolonged (P < 0.05) cough latency, reduced the number of coughs, and significantly increased (P < 0.05) phenol red excretion in ammonia-induced cough mice. Twenty-five metabolites related to cough and 38 metabolites related to sputum excretion were identified by UHPLC-LTQ-orbitrap-MS. Changes in the metabolism of linoleic acid, arachidonic acid, glycerophospholipid, alanine, aspartic acid and glutamic acid, pentose and glucuronate interconversions, and lysine degradation were evident with DPD treatment of ammonia-induced cough mice. Changes in the metabolism of linoleic acid, taurine and hypotaurine, glycerophospholipid, purines and pyrimidines, arachidonic acid and the biosynthesis of unsaturated fatty acids after DPD treatment were related to phenol red excretion. Linoleic acid metabolism, arachidonic acid metabolism and glycerophospholipid metabolism are common regulatory pathways by which DPD appears to exert its antitussive and expectorant activity. These metabolic pathways are closely related to anti-inflammatory pathways, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and apoptosis. This study clarifies the antitussive and expectorant activity and mechanism of DPD.

Background: Enterotoxigenic Escherichia coli (ETEC) infection is a primary cause of livestock diarrhea. Therefore, effective vaccines are needed to reduce the incidence of ETEC infection. Objectives: Our study aimed to develop a multivalent ETEC vaccine targeting major virulence factors of ETEC, including enterotoxins and fimbriae. Methods: SLS (STa-LTB-STb) recombinant enterotoxin and fimbriae proteins (F4, F5, F6, F18, and F41) were prepared to develop a multivalent vaccine. A total of 65 mice were immunized subcutaneously by vaccines and phosphate-buffered saline (PBS). The levels of specific immunoglobulin G (IgG) and pro-inflammatory cytokines were determined at 0, 7, 14 and 21 days post-vaccination (dpv). A challenge test with a lethal dose of ETEC was performed, and the survival rate of the mice in each group was recorded. Feces and intestine washes were collected to measure the concentrations of secretory immunoglobulin A (sIgA). Results: Anti-SLS and anti-fimbriae-specific IgG in serums of antigen-vaccinated mice were significantly higher than those of the control group. Immunization with the SLS enterotoxin and multivalent vaccine increased interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) concentrations. Compared to diarrheal symptoms and 100% death of mice in the control group, mice inoculated with the multivalent vaccine showed an 80% survival rate without any symptom of diarrhea, while SLS and fimbriae vaccinated groups showed 60 and 70% survival rates, respectively. Conclusions Both SLS and fimbriae proteins can serve as vaccine antigens, and the combination of these two antigens can elicit stronger immune responses. The results suggest that the multivalent vaccine can be successfully used for preventing ETEC in important livestock.

Aim To explore the roles of miRNA-132 and its related proteins(Mecp2, CREB)in the mechanism of methamphetamine(MA)-induced neurotoxicity and dependence.Methods The rats were intraperitioneally injected(ip)with MA(10 mg·kg-1·d-1)to establish methamphetamine dependence model with different dependent time courses of 1 week, 2 weeks, and 4 weeks respectively.The miRNA-132 and Mecp2 mRNA were detected by RT-qPCR, and the Mecp2, p-Mecp2, CREB and p-CREB proteins were detected by Western blot in the tissues of frontal cortex and hippocampus.Results In the frontal cortex, the miRNA-132 and Mecp2 mRNA were up-regulated in MA-dependent groups(P<0.05 and P<0.01), while the Mecp2 protein were down-regulated(P<0.01).MA could promote the phosphorylation of Mecp2 protein in the frontal cortex(P<0.01).In hippocampus, the miRNA-132 was down-regulated in the MA-dependent groups, but Mecp2 mRNA was up-regulated(P<0.05).Mecp2 protein increased in MA-dependent 1 week group(P<0.05), and then recovered with the prolonged time of MA dependence, then decreased in MA-dependent 4 weeks groups(P<0.05)in hippocampus.The phosphorylation level of Mecp2 was significantly decreased in the 1 week group(P<0.01), and then increased in the 2 weeks group(P<0.01)in hippocampus.Conclusions MA could induce an abnormal expression of miRNA-132 in the frontal cortex and hippocampus, and miRNA-132 might inhibit the translation of Mecp2 mRNA and induce the decrease expression of Mecp2 protein in the frontal cortex.But in hippocampus, miRNA-132 does not show the correlation with the Mecp2 expression trend of the frontal cortex.And miRNA-132 regulation does not depend on the expression of Mecp2 in hippocampus.

Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. In order to solve the problem of drug abuse, it is of great theoretical value and practical significance to carry out all-round and multi-level scientific research on drug-related issues. Based on the current situation of drug abuse, this article reviews research progresses on the epidemiology of methamphetamine abuse, the monitoring technology, the basic researches on toxicity damage, the withdrawal drug screening, the related clinical comorbidity and the testing technologies, comprehensively presenting the development trend of methamphetamine abuse related issues.
Amphetamine-Related Disorders/epidemiology* ; Heroin ; Humans ; Illicit Drugs ; Methamphetamine/adverse effects* ; Substance Abuse Detection

Sea buckthorn(Hippophae rhamnoides) is widely distributed, with abundant resources, a long history of application, and rich nutrition and high medicinal value. Therefore, it has attracted extensive attention from researchers at home and abroad. The focus of attention is mainly on sea buckthorn fruit, but with weak research and development of sea buckthorn leaves. In order to develop and utilize abundant resources of sea buckthorn leaves, this paper systematically reviewed domestic and foreign literatures and summarized the current application, harvesting and processing, chemical constituents and pharmacological activities of sea buckthorn leaves. Sea buckthorn leaves have a wide development and utilization value in food raw materials(like a substituting-for-tea plant), pharmaceutical raw materials and animal feed. Modern studies have shown that the leaves of sea buckthorn are rich in polysaccharides, flavonoids, polyphenols, triterpenes and steroids, as well as vitamins(especially vitamin C), proteins, amino acids and mineral elements. It has various pharmacological effects, such as anti-obesity, hypoglycemia, anti-oxidation, antibacterial, anti-inflammatory and anti-cardiovascular diseases. Domestic and foreign studies have showed that sea buckthorn leaves have important development and utilization prospects, and are worth further study and development.
Animals ; Flavonoids ; Fruit ; Hippophae ; Plant Leaves ; Polyphenols

Objective:To investigate the clinical characteristics of old patients with spinal cord injury. Methods:From January 1, 2013 to December 31, 2019, totally 386 old (≥ 60 years) patients with spinal cord injury were enrolled. Their gender, age, etiology, American Spinal Injury Association Impairment Scale (AIS) and complications were analyzed. Results:In the old patients with spinal cord injury, traumatic spinal cord injury was more common in males (71.17%) and non-traumatic spinal cord injury was more common in females (56.19%). Fall on level surface was the most important cause of spinal cord injury both in old men (28.83%) and women (24.76%). Tumor (19.05%) was the most common non-traumatic cause of spinal cord injury in old female patients. Cervical segment (78.46%) was the most common site of injury in old traumatic spinal cord injury, while thoracic segment (52.14%) was the most common site of injury in non-traumatic spinal cord injury. Grade D (38.08%) was the most common AIS grade, followed by grades C (28.76%), A (21.50%), and B (11.66%). Spinal canal stenosis (23.31%) played an important role in the etiology of old spinal cord injury. Neuralgia, venous thrombosis of lower extremities and urinary tract infection were the most common complications in old patients with spinal cord injury. Conclusion:Fall on level surface is the leading cause of spinal cord injury in old patients, and the proportion of fall in the etiology of old spinal cord injury tends to increase with age. It is important to take effective measures to avoid falling in the old adults to prevent spinal cord injury.

Objective:To investigate the outcome of neurological function and the clinical characteristics of complications in children with spinal cord injury. Methods:From 2011 to 2019, children under 15 years old with spinal cord injury were selected in our hospital. Their level of injury and American Spinal Injury Association Impairment Scale (AIS) at one month, three months and one year were recorded. And the complications such as pressure ulcers/scald, urinary tract infection, hydronephrosis/vesicoureteral reflux, constipation, osteoporosis/fracture, deep vein thrombosis, neurodynia, heterotopic ossification, scoliosis and hip dysplasia were analyzed. Results:Of 159 individuals, 41 were boys and 118 were girls, the average age at injury was (6.08±2.57) years. The main cause of spinal cord injury was sports accidents (47.8%), and the main injury sites were thoracic spinal cord injury (89.3%). The cause of spinal cord injury was correlated with age at injury (r = -0.160, P = 0.044), gender (r = -0.458, P < 0.001) and injury sites (r = -0.249, P = 0.002). Complete spinal cord injury counted for 71.7%, and the AIS grade at one month was correlated with that at twelve months (r = 0.984, P < 0.001). The main complications were urinary tract infection (69.2%), constipation (67.9%), hydronephrosis/vesicoureteral reflux (37.7%), scoliosis (25.8%) and hip dysplasia (25.2%). The incidence of ulcers/scald was correlated with injury site (r = 0.179, P = 0.024). The AIS grade three months after injury was significantly correlated with urinary tract infection, constipation, scoliosis and hip dysplasia (|r| > 0.227, P < 0.01). The incidence of ulcers/scald was correlated with osteoporosis/fracture (r = 0.208, P < 0.01). The incidence of urinary tract infection was significantly correlated with hydronephrosis/vesicoureteral reflux, constipation, scoliosis and hip dysplasia (r > 0.261, P < 0.001), as well as osteoporosis/fracture (r = 0.195, P < 0.05). The incidence of hydronephrosis/vesicoureteral reflux was significantly correlated with constipation, osteoporosis/fracture, scoliosis and hip dysplasia (r > 0.146, P < 0.01). The incidence of constipation was significantly correlated with scoliosis and hip dysplasia (r > 0.313, P < 0.01), as well as osteoporosis/fracture (r = 0.160, P < 0.05). The incidence of osteoporosis/fracture was significantly correlated with scoliosis and hip dysplasia (r > 0.342, P < 0.01). The incidence of scoliosis was significantly correlated with hip dysplasia (r = 0.818, P < 0.001). Conclusion:The recovery of neurological function after spinal cord injury in children is closely correlated to AIS. The outcome of complete spinal cord injury is poor. The common complications after spinal cord injury in children demonstrate specific age characteristics, and the incidence of urinary tract infection, constipation, hydronephrosis/vesicoureteral reflux, scoliosis and hip dysplasia are common complications, which need more attention.

Objective:To explore the clinical manifestations and MRI features of pediatric spinal cord injury (SCI) after back bend. Methods:A retrospective study was performed. All the medical records and MRI images of children with SCI after back bend were identified in Beijing Bo'ai Hospital from January 1st, 2002 to August 31st, 2020. Results:A total of 120 SCI children after back bend were reviewed, out of whom 119 cases were girls, one case was boy. The age ranged from 38 to 162 months, with the median age of 76 months. More cases were discovered in July and September every year (32 cases, 26.7%), as well as in weekends (67 cases, 55.8%). The main clinical manifestations were sensory and motor dysfunction of both lower limbs (120 cases, 100%), bladder and bowl incontinence (120 cases, 100%). The common first symptoms included sudden attack of lumbar pain (39 cases, 32.5%), lower limbs paralysis (30cases, 25.0%) and leg pain (10 cases, 8.3%). The peak time of symptoms ranged from five minutes to two days, with the median time of 50 minutes. The MRI features of 104 children with SCI within one week after back bend were as follows: the abnormal signals of MRI in spinal cord involved lower cervical and all the following segments of spinal cord. The number of the segments of spinal cord with abnormal signals ranged from two to 15, with the median of seven segments. The most common segments with abnormal signals were T₉ (96 cases, 92.3%), T₁₀ (96 cases, 92.3%) and T₁₁ (90 cases, 86.5%). Among the cases followed up, 48 cases with complete injury demonstrated a vast and serous spinal cord atrophy (SCA) below the injury segments as early as 37 days after the injury, the SCA would become worse at the chronic stage and maybe involve the spinal cord above the injury segments. In 31 cases with incomplete injury, the abnormal signals of MRI in spinal cord were limited in the lumbar enlargement, with a various degree of SCA at the late stage. All the cases were diagnosed as SCI without radiologic abnormality, out of whom 89 (74.2%) cases suffered from thoracic complete SCI, 31 (25.8%) cases suffered thoracic or lumbar incomplete SCI. The common complications included scoliosis, hip joint dysplasia, urinary tract infection, hydronephrosis, osteoporosis, pathological fracture of lower limbs and valgus knee. Conclusion:The main clinical symptoms of pediatric SCI after back bend were sudden lumbar pain, sensory and motor dysfunction of both lower limbs, and bladder and bowl incontinence. Most of the cases were thoracic complete SCI, the MRI features at the early stage were multiple segments of abnormal signals of spinal cord around T₉ and T₁₀, and later an extensive severe SCA below the injury segments to the conus medullaris, accompanied by the SCA above the injury segments.