Mechanism of Fuyuan Xingnao Decoction in the treatment of cerebral infarction based on network pharmacology and molecular docking / 国际中医中药杂志

Objective:To explore the mechanism of Fuyuan Xingnao Decoction in treatment of cerebral infarction based on network pharmacology and molecular docking.Methods:The active components and action targets of Fuyuan Xingnao Decoction were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP),Traditional Chinese Medicine Integrated Database (TCMID),Bioactivity data of small organic molecules (PubChem),Universal Protein (Uniprot) and Swiss Target Prediction database platform. The databases of GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and Drug Bank and Pharmacogenomics Knowledgebase (PharmGKB) were used to screen targets of cerebral infarction. The drug target genes in Fuyuan Xingnao Decoction were intersected with those of cerebral infarction, the intersecting targets were introduced into Cytoscape 3.8.2 software to construct the component target network, and the PPI protein interaction network was constructed by using STRING analysis platform and Cytoscape 3.8.2 software to screen the core targets. Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) function enrichment analysis were carried out on the common target genes of Fuyuan Xingnao Decoction and cerebral infarction disease to obtain the relevant signal pathways. Finally, AutoDock and Pymol software were used for molecular docking between the predicted target and its corresponding components.Results:After screening, 80 effective components of Fuyuan Xingnao Decoction for treatment of cerebral infarction and 214 common targets of Fuyuan Xingnao Decoction and cerebral infarction were obtained. The core targets such as MAPK1, RELA, TP53, JUN, AKT1 and HSP90AA1 were related to the key targets of cerebral infarction, and they participated in the biological process of regulating the response to drugs, lipopolysaccharide and oxygen level, etc. The cell composition involved membrane raft, membrane micro region and nerve cell body, etc. Molecular functions mainly focused on nuclear receptor activity, ligand activated transcription factor activity, DNA binding transcription factor binding, etc.; it also involved in signal pathway of lipid and atherosclerosis, chemical carcinogen and receptor activation, fluid shear stress and atherosclerosis, etc. Molecular docking showed that good binding activities were seen between Quercetin and HSP90AA1 (-9.4 kJ/mol), between Kaempferol and HSP90AA1 (-9.4 kJ/mol), between Isorhamnetin and HSP90AA1 (-9.1 kJ/mol), and between Quercetin and JUN (-8.6 kJ/mol).Conclusion:Fuyuan Xingnao Decoction can prevent and treat cerebral infarction by regulating vascular endothelial function, promoting blood circulation, repairing and improving neural function, protecting blood-brain barrier, reducing cell apoptosis, and regulating immune and inflammatory response.

Disease burden of chronic kidney disease attributable to metabolic factors in Jiangsu Province in 1990 -2019 / 公共卫生与预防医学

Objective To analyze the burden of chronic kidney disease (CKD) attributable to metabolic factors in Jiangsu Province from 1990 to 2019, and to provide evidence for the formation and implementation of intervention policies. Methods Using data from Jiangsu Province from the 2019 Global Burden of Disease Study (GBD 2019), mortality and disability-adjusted life-years (DALYs) were selected as indicators for analysis and standardized with the age structure of the world standard population. The effects of three metabolic factors including high systolic blood pressure (SBP), high fasting glycaemic index (FPG) and high body mass index (BMI) on the disease burden of CKD were analyzed, and the attributable disease burden by gender and age was compared. Results The rank of the three attributable risk factors was high SBP, high FPG, and high BMI. Standardized mortality rates attributable to high SBP, high FPG, and high BMI all showed an overall upward trend from 1990 to 2019, with annual average percent changes (AAPCs) of 0.3%, 0.0%, and 2.8%, respectively. Age-standardized DALYs attributed to high SBP and high BMI showed increasing trends, with the AAPCs of 0.5% and 3.1% (both P＜0.05), respectively. There was no statistical significance of high FPG (P > 0.05). Mortality and disease burden attributed to high SBP both showed upward trends with increasing age. Age-standardized mortality and age-standardized DALYs attributed to high FPG peaked at 45-49 and 50-54 age-group, respectively. Both age-standardized mortality and age-standardized DALYs attributed to high BMI peaked at ages 60-64 age-group. Conclusion The trends of mortality and DALYs attributed to the three risk factors can reflect the changes of population structure and lifestyle in Jiangsu Province in the past 30 years to a certain extent. Early screening of population at high risk of CKD and targeted provision of health policies can reduce the mortality and disease burden of CKD.

Data-driven engineering framework with AI algorithm of Ginkgo Folium tablets manufacturing

Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate Cpk integrated Bootstrap-t. The Cpk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.

Systemic lupus erythematosus with acquired hemophilia A: A case report and literature review / 中南大学学报(医学版)

Systemic lupus erythematosus (SLE) complicated with acquired hemophilia A (AHA) is a rare condition with frequently delayed diagnosis and a high mortality rate, so it is necessary to strengthen the understanding of this disease. In this study, the characteristics and treatment in 1 case of SLE complicated by AHA is reported and analyzed, and a literature review is conducted. The patient was a 29-year-old young female with a 10-year history of SLE, the main clinical manifestation was severe abdominal bleeding. Laboratory tests revealed that the activated partial thromboplastin time (APTT) was notably prolonged (118.20 s), and the coagulation factor VIII activity (FVIII꞉C) was extremely decreased (0.20%) with high-titer of factor VIII (FVIII) inhibitor (31.2 BU/mL). After treating with high-dose glucocorticoid, immunoglobulin, cyclophosphamide, rituximab, blood transfusion, and intravenous infusion of human coagulation FVIII, the coagulation function and coagulation FVIII꞉C were improved, and FVIII inhibitor was negative without serious adverse reactions. During the next 5-year follow-up, the patient's condition was stable and no bleeding occurred. In the case of coagulation dysfunction in SLE, especially with isolated APTT prolongation, AHA should be screened. When the therapeutic effects of glucocorticoid combined with immunosuppressants are not desirable, rituximab could be introduced.

Simultaneous determination of fifteen components in Niuhuang Jiangya Pills by UPLC-Q Exactive-Orbitrap MS / 药学学报

An ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (UPLC-Q Exactive-Orbitrap MS) method for the simultaneous determination of 15 compounds (taurocholic acid, 7-keto-3α,12-α-dihydroxycholanic acid, glycocholic acid, 3-oxo-7α,12α-hydroxy-5β-cholanoic acid, taurochenodeoxycholic acid, 3α-hydroxy-7-oxo-5β-cholanic acid, hyocholic acid, sodium taurodeoxycholate, hyodeoxycholic acid, cholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, taurolithocholic acid sodium salt, chenodeoxycholic acid, deoxycholic acid) in Niuhuang Jiangya Pills was established. The separation was performed on a Thermo Fisher Scientfic Bremen HYPERSIL GOLD C18 column (100 mm × 2.1 mm, 1.9 μm). Methanol and water (containing 0.1% formic acid)were adopted as the mobile phase by gradient elution．MS detection was performed with multiple reaction monitoring mode．The results showed that fifteen compounds had a good linearity within their respective concentration ranges (r > 0.999 0). The average recovery rates were 93.7%- 105.2% (n = 9). The established method was used to determine the content of 15 batches of samples, and the results showed that the content of cholic acid was quite different. The present study provides an important reference for the overall quality control of Niuhuang Jiangya Pills.

The value of exhaled nitric oxide in assessing the risk of acute exacerbation and guiding the use of ICS in patients with COPD / 中国医师杂志

Objective:To explore the predictive value of exhaled nitric oxide (FeNO) for the risk of acute exacerbation in stable chronic obstructive pulmonary disease (COPD) patients over the next year and evaluate whether it can guide the use of inhaled corticosteroids (ICS).Methods:This study was a multicenter, retrospective and observational cohort study. The subjects of this study were stable COPD patients who were hospitalized in 12 hospitals in Hunan Province and Guangxi from January 2017 to December 2021. The patient′s basic Demography information, previous acute exacerbation history, pulmonary function, FeNO, chronic obstructive pulmonary disease assessment test questionnaire (CAT) score, modified British Medical Research Council dyspnea questionnaire (mMRC) score, chronic obstructive pulmonary disease control questionnaire (CCQ) score, and detailed treatment plan were collected. Based on FeNO 25 ppb, patients were divided into a high FeNO group and a normal FeNO group. All patients were followed up for 1 year and information on acute exacerbation was recorded.Results:A total of 825 patients were included, aged (63.5±9.1)years, with a median of 25 ppb of FeNO. A number of 825 patients were followed up for 1 year, of which 262(31.8%) experienced acute exacerbation. Multivariate logistic regression found that FeNO, CAT score, smoking cessation, and past history of acute exacerbation were independent factors predicting acute exacerbation in COPD patients in the next year (all P<0.05). High FeNO was a protective factor for acute exacerbation in COPD patients in the next year, with an OR value of 0.10 ( P<0.001). Further analysis found that the proportion of patients in the high FeNO group using ICS was significantly higher than that in the normal FeNO group [58.8%(247/420) vs 48.6%(197/405), P=0.003]. In the high FeNO group, using ICS can reduce the incidence of acute exacerbation of COPD in the next year [8.9%(22/247) vs 15.6%(27/173), P<0.05], while in the normal FeNO group, there was no statistically significant difference in the frequency of acute exacerbation between patients using ICS and those not using ICS ( P>0.05). Conclusions:FeNO is an independent factor predicting the acute exacerbation of COPD in the next year, and patients with high FeNO levels may consider using ICS in combination.

Symptom scores of patients with chronic obstructive pulmonary disease and their response to different inhalation drug treatments / 中国医师杂志

Objective:To analyze the response of patients with chronic obstructive pulmonary disease (COPD) with multiple and few symptoms to different inhalation drugs, including acute exacerbation and symptom changes.Methods:This study was a multi center, retrospective Cohort study. The subjects of this study were patients with chronic obstructive pulmonary disease in stable stage in 12 hospitals in Hunan and Guangxi from December 2016 to February 2022. Demographics data, lung function, Chronic Obstructive Pulmonary Disease Assessment test questionnaire (CAT) score, modified British Medical Research Council dyspnea questionnaire (mMRC) score and inhalation drug scheme of patients were collected. According to the CAT and mMRC scores, patients were divided into a multi symptom group (CAT≥10 points or mMRC≥2 points) or a few symptom group (CAT<10 points and mMRC<1 point); Subsequently, they were divided into four subgroups based on the inhalation drug regimen: long-acting anticholinergic drugs (LAMA) group, long-acting β2-receptor agonists (LABA)+ inhaled corticosteroids (ICS) group, LABA+ LAMA group, and LABA+ LAMA+ ICS group. All patients were followed up for 1 year, with minimum clinical improvement (MCID) defined as a decrease of ≥2 points in the patient′s CAT score at 6 months, and clinical symptom deterioration (CSD) defined as an increase of ≥2 points in the patient′s CAT score at 6 months.Results:A total of 929 patients with chronic obstructive pulmonary disease were included, including 719(77.4%) with multiple symptoms and 210(22.6%) with few symptoms. There was no statistically significant difference in MCID, CSD, acute exacerbation, hospitalization frequency, and mortality rate among subgroups of asymptomatic COPD patients treated with different inhalation drug regimens (all P>0.05). Among patients with multiple symptoms of chronic obstructive pulmonary disease, compared to those who use LAMA or LABA+ ICS, those who used LABA+ LAMA or LABA+ LAMA+ ICS were more likely to obtain MCID and had a more significant improvement in CAT scores, and the risk of acute exacerbation is lower (all P<0.05). Conclusions:Lesser symptomatic COPD patients should receive single drug LAMA as the initial inhalation treatment drug, while multi symptomatic COPD patients should receive LABA+ LAMA as the initial inhalation treatment drug.

Differences between Chinese men and women with adult-onset non-radiographic axial spondyloarthritis / 中华风湿病学杂志

Objective:To explore the clinical characteristics of adult-onset non-radiographic axial spondyloarthritis (nr-axSpA) in different genders.Methods:A total of 662 patients with adult-onset nr-axSpA (age at disease onset ≥16 years) who visited the Rheumatology Department of the First Affiliated Hospital of Shantou University Medical College from 1999 to 2020 were included in the study. Comparisons of baseline demographic and clinical characteristics between different genders were performed.Results:Overall, the male-to-female ratio was 1.17∶1, and the prevalence of human leukocyte antigen-B27 (HLA-B27) positivity was 71.8%(475/662). The median baseline disease duration and age at diagnosis was 1.6 (0.5, 4.0) years and 25.0 (21.0, 33.0) years respectively. The males had a significantly earlier age at disease onset and diagnosis [21.0 (18.0, 28.0) vs 25.0 (21.0, 30.0), Z=5.63, P<0.001; 24.0 (19.0, 32.0) vs 27.0 (23.0, 34.5), Z=4.90, P<0.001, respectively] than females. HLA-B27 positivity was more frequent in males than in females [78.4% (280/357) vs 63.9%(195/305), χ2=17.06, P<0.001]. The prevalence of inflammatory back pain (IBP), morning stiffness, nocturnal pain, enthesitis, hip and groin pain were higher in males, whereas females showed a higher prevalence of small joint involvement of the hands. At baseline, males had higher median ankylosing spondylitis disease activity score (ASDAS)-C-reaction protein (CRP) [3.0(2.3, 3.8) vs 2.4(2.0, 3.0), Z=5.59, P<0.001] and a greater prevalence of high disease activity ASDAS-CRP>2.1 [81.9%(185/227) vs 67.9%(133/195), χ2=11.08, P=0.001] than females. The proportions of male patients with elevated CRP levels and erythrocyte sedimentation rate (ESR) were also higher than those of female patients [49.0%(175/357) vs 27.9%(85/305), χ2=30.85, P<0.001; 49.3%(176/357) vs 33.4%(102/305), χ2=16.98, P<0.001, respectively]. Conclusion:The adult-onset nr-axSpA in China is characterized by a comparable sex ratio. Males have an earlier age at disease onset and are higher HLA-B27 positivity with higher prevalence of IBP, enthesitis, hip and groin pain, as well as high disease activity.

Research progress in risk prediction of acute exacerbations of chronic obstructive pulmonary disease / 中国医师杂志

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by persistent respiratory symptoms and airflow limitation. Acut exacerbations (AE) are one of the main outcomes in patients with COPD. AE of COPD will accelerate hospitalization rates, increase mortality, and reduce quality of life. Therefore, it is of importance to identify predictors of AE in patients with COPD. This review mainly summarizes the predictive factors associated with AE from the clinical characteristics of patients, biomarkers, and composite index prediction models.

A case of acute poisoning caused by oral administration of large dose hexazinone / 中华劳动卫生职业病杂志

Hexazinone is a post-emergence herbicide/arboricides, and its acute poisoning has rarely been reported. Hexazinone is low-toxic to humans, but mass intake of hexazinone would still lead to organ impairment. This article analyzes a case of acute hexazinone poisoning from the poisoning treatment center of our hospital, and summarizes the symptoms and treatment effects of hexazinone poisoning, which is aimed at improving the comprehension, diagnosis and treatment of the disease.

Practice and effect analysis on construction of clinical medical research center of cardiovascular diseases / 中华医学科研管理杂志

Objective:This article takes the practical experience of the construction of the cardiovascular disease clinical medicine research center in Nanjing First Hospital as an example to provide reference for institutions preparing to build a clinical research center.Methods:The center conducts top-level design based on clinical needs, and this study systematically elaborates the construction of the center from management mechanisms, research platforms, collaborative networks, team building and international cooperation.Results:The center has made remarkable progress in clinical research, scientific and technological innovation, transformation and promotion, standard formulation, and technology leading. On the basis of an international perspective, the level of regional diagnosis and treatment has been improved by optimizing the structure of subject talents, and focusing on the clinical needs of cardiovascular subspecialty.Conclusions:Taking the construction of the clinical medicine center as an opportunity, integrating superior resources, improving the level of disease diagnosis, treatment and service and enhancing international academic influence are effective measures to accelerate the development of health services and deepen medical reforms.

Mechanisms of bone marrow mesenchymal stem cells plus normothermic mechanical perfusion alleviating hepatocyte apoptosis after donation after cardiac death transplantation in rats / 中华器官移植杂志

Objective:To explore the effect and possible mechanism of normal temperature mechanical perfusion(NMP)plus bone marrow mesenchymal stem cells(BMMSCs)on early endoplasmic reticulum stress(ERs)and cellular apoptosis after donation after cardiac death(DCD)donor liver transplantation.Methods:BMMSCs were isolated and cultured by adherence method.Sixty Sprague-Dawley(SD)rats were randomly divided into five groups of sham operation(sham), static cold storage(SCS), NMP, BMMSC and NMP plus BMMSCs(BP)( n=12 each). Liver tissue and serum sample of each group were harvested at Day 1/7 post-operation.Hematoxylin-eosin(HE)staining was employed for observing pathological changes of liver tissue; TdT-mediated dUTP nick end labeling(TUNNEL)staining for detecting cellular apoptosis; immunohistochemistry for detecting the expression of hepatocyte transcription factor C/EBP homologous protein(CHOP); Western blot for detecting the expressions of GRP-78, p-PERK, ATF4, CHOP and cleaved caspase-3. Results:Compared with SCS group, hepatic injury and inflammation significantly declined in NMP, BMMSC and BP groups and improvement of hepatic injury was the most pronounced in BP group.Cellular apoptosis lessened markedly in BP group at Day 1/7 as compared with SCS group and the difference was statistically significant.The expressions of ERs-related proteins GRP-78, p-PERK and ATF4 spiked in SCS group and the expressions of pro-apoptotic proteins CHOP and cleaved caspase-3 were significantly elevated and declined markedly in BP group.And the difference was statistically significant.Conclusions:BMMSCs plus NMP can significantly improve hepatocyte apoptosis and inflammatory response after DCD donor liver transplantation.And its mechanism may be correlated with suppressing early endoplasmic reticulum stress of hepatocytes.

Effect of heme oxygenase-1 modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion on intestinal barrier function in Brown Norway rats with acute rejection of liver transplantation / 中华肝胆外科杂志

Objective:To investigate the effect of heme oxygenase-1 (HO-1) modified bone marrow mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP) on the intestinal barrier function in rats with acute rejection of liver transplantation.Methods:Specific pathogen free 2 male Brown Norway (BN) rats (4-5 weeks, 40-60 g) were used to isolat BMMSCs, and HO-1 was infected by adenovirus. Of 24 male Lewis rats (7-8 weeks old, 200-220g) were used as donors, 30 male BN rats (8-9 weeks old, 220-240 g) were used as recipients. Acute rejection models of orthotopic liver transplantation were established in rats using two cuff technique. BN recipient rats were randomly divided into five groups: sham group, abdomen of the mice was open and closed within 30 min; NMP livers were simply mechanically perfused for 4 h; the BMP group were perfused with BMMSCs through the portal vein; the HBP group were perfused with HO-1/BMMSCs through the portal vein; the FK506 livers were mechanically perfused for 4 h and administered intragastrically of tacrolimus daily following surgery, 6 per group, on days 14 after surgery, the relevant indicators were taken and the rejection activity index (RAI) changes were investigated. The changes of intestinal pathological were analyzed by HE staining and transmission electron microscope, the expression levels of zonula occludens-1 (ZO-1) and occludin protein in intestinal tissue were detected by Western blotting, the concentrations of lipopolysaccharide, D-lactic acid and diamine oxidase (DAO) in serum were detected by ELISA.Results:The RAI of HBP group (2.80±0.84) and FK506 group (2.20±0.84) were significantly lower than that of NMP group (7.60±1.14) and BMP group (6.00±1.58), the differences were statistically significant (all P<0.05). The intestinal villi in NMP group were significantly sparse, wrinkled and disorderly arranged while the degree of intestinal injury in BMP group, HBP group and FK506 group were more mitigated. Electron microscope observation showed that the microvilli of intestinal epithelial cells in HBP group were rich and orderly, and the tight junction structure between cells was complete. The protein expression levels of ZO-1 and Occludin in the intestinal tissues of HBP group [(0.87±0.06) (1.28±0.26)] were higher than those of NMP group [(0.41±0.12) (0.27±0.18)] and FK506 group [(0.52±0.15) (0.63±0.22)], the differences were statistically significant (all P<0.05). The concentration of lipopolysaccharide, D-lactic acid and DAO in serum of HBP group was lower than those of NMP group and FK506 group, the differences were statistically significant (all P<0.05). Conclusion:HO-1/BMMSCs combined with NMP protects the intestinal mucosal barrier function of BN rats with acute rejection after liver transplantation.

Effects of upper limb robot-assisted training on cognition and upper limb motor function for subacute stroke patients / 中国康复理论与实践

ObjectiveTo investigate the effects of upper limb robot-assisted training on cognitive function, upper limb motor function and activity of daily living for subacute stroke patients. MethodsFrom September, 2019 to September, 2020, 65 subacute stroke hemiplegic patients with cognitive impairment were randomly divided into control group (n = 32, two cases dropped) and experimental group (n = 33, three cases dropped). Both groups accepted conventional occupational therapy; and then, the control group accepted conventional cognitive training, while the experimental group accepted upper limb robot-assisted training, for four weeks. They were assessed with Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI) before and after treatment. ResultsThe scores of MoCA, MMSE, FMA-UE and MBI improved after treatment in both groups (t > 22.11, Z > 4.79, P < 0.001), the MoCA total score and some item-scores, MMSE total score and some item-scores, FMA-UE total score and the score of arm, and score of MBI improved more in the experimental group than in the control group (t > 2.06, Z > 3.19, P < 0.05). ConclusionUpper limb robot-assisted training could facilitate to improve the cognitive function, upper limb motor function and activities of daily living in subacute stroke patients.

Effect of parent-child cooperative music therapy on children with autism spectrum disorder and their mothers: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To study the effect of parent-child cooperative music therapy on the core symptoms of children with autism spectrum disorder (ASD) and their mothers.@*METHODS@#In this prospective study, 112 children with ASD and their mothers were divided into a music therapy group and an applied behavior analysis (ABA) group using a random number table (n=56 each). The children in the ABA group were treated with ABA, and those in the music therapy group were given parent-child cooperative music therapy in addition to the ABA treatment. The duration of intervention was 8 weeks for both groups. Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC), Parenting Stress Index-Short form (PSI-SF), Family APGAR Index, and Herth Hope Index (HHI) were used to evaluate the core symptoms of children with ASD and the parenting stress, family APGAR index, and hope level of mothers before and after intervention.@*RESULTS@#A total of 100 child-mother dyads completed the whole study, with 50 child-mother dyads in each group. After intervention, the children in the music therapy group had significantly lower total score of ABC scale and scores of sensation, social interaction, and somatic movement, as well as a significantly lower total score of CARS than those in the ABA group (P<0.05). After intervention, compared with the mothers in the ABA group, the mothers in the music therapy group had significantly higher total score of PSI-SF and score of parent-child dysfunctional interaction, significantly higher total score of HHI and scores of each dimension, and significantly higher total score of APGAR and scores of cooperation and intimacy (P<0.05).@*CONCLUSIONS@#Parent-child cooperative music therapy combined with ABA can alleviate the core symptoms of children with ASD, reduce the parenting stress of their mothers, and improve family APGAR index and hope level.

A long-term ischemic stroke risk score model in patients aged 60 years and older with obstructive sleep apnea: a multicenter prospective cohort study / 南方医科大学学报

OBJECTIVE@#To analyze the independent risk factors of long-term ischemic stroke and establish a nomogram for predicting the long-term risks in elderly patients with obstructive sleep apnea (OSA).@*METHODS@#This multicenter prospective cohort study was conducted from January, 2015 to October, 2017 among consecutive elderly patients (≥60 years) with newly diagnosed OSA without a history of cardio-cerebrovascular diseases and loss of important clinical indicators. The follow-up outcome was the occurrence of ischemic stroke. The baseline demographic and clinical data, sleep parameters, laboratory and ultrasound results were collected from all the patients, who were randomized into the modeling group (n=856) and validation group (n=258) at a 3∶1 ratio. LASSO regression was used for variable reduction and dimension screening, and the risk score prediction model of ischemic stroke was established based on Cox proportional hazard regression.@*RESULTS@#In the total of 1141 patients enrolled in this study, 58 (5.08%) patients experienced ischemic stroke during the median follow-up of 42 months (range 41-54 months). The cumulative incidence of ischemic stroke was 5.14% in the model group and 4.91% in the verification group (P < 0.05). Age (HR=3.44, 95% CI: 2.38- 7.77), fasting blood glucose (FPG) (HR=2.13, 95% CI: 1.22-3.72), internal diameter of the ascending aorta (HR=2.60, 95% CI: 1.0- 4.47), left atrial anteroposterior diameter (HR=1.98, 95% CI: 1.75-2.25) and minimum oxygen saturation (LSpO2) (HR=1.57, 95% CI: 1.20-1.93) were identified as independent risk factors for ischemic stroke (P < 0.05 or 0.01). A long-term ischemic stroke risk score model was constructed based the regression coefficient ratios of these 5 risk variables. Before and after the application of the Bootstrap method, the AUC of the cohort risk score model was 0.84 (95% CI: 0.78- 0.90) and 0.85 (95% CI: 0.78- 0.89) in the model group and was 0.83 (95% CI: 0.73-0.93) and 0.82 (95%CI: 0.72-0.90) in the verification group, respectively, suggesting a good prediction efficiency and high robustness of the model. At the best clinical cutoff point, the cumulative incidence of ischemic stroke was significantly higher in the high-risk group than in the low-risk group (P=0.021).@*CONCLUSION@#This model can help to identify high-risk OSA patients for early interventions of the risks of ischemic stroke associated with OSA.

Lowered expression of CCN5 in endometriotic tissues promotes proliferation, migration and invasion of endometrial stromal cells / 南方医科大学学报

OBJECTIVE@#To explore the expression of CCN5 in endometriotic tissues and its impact on proliferation, migration and invasion of human endometrial stromal cells (HESCs).@*METHODS@#We collected ovarian endometriosis samples from 20 women receiving laparoscopic surgery and eutopic endometrium samples from 15 women undergoing IVF-ET for comparison of CCN5 expression. Cultured HESCs were transfected with a recombinant adenovirus Ad-CCN5 for CCN5 overexpression or with a CCN5-specific siRNA for knocking down CCN5 expression, and the changes of cell proliferation, migration and invasion were evaluated using CCK-8 assay, wound healing assay and Transwell chamber assay. RT-qPCR and Western blotting were used to examine the expression levels of epithelial-mesenchymal transition (EMT) markers including E-cadherin, N-cadherin, Snail-1 and vimentin in HESCs with CCN5 overexpression or knockdown.@*RESULTS@#CCN5 expression was significantly decreased in ovarian endometriosis tissues as compared with eutopic endometrium samples (P < 0.01). CCN5 overexpression obviously inhibited the proliferation, migration and invasion of HESCs, significantly increased the expression of E-cadherin and decreased the expressions of N-cadherin, Snail-1 and vimentin (P < 0.01). CCN5 knockdown significantly enhanced the proliferation, migration and invasion of HESCs and produced opposite effects on the expressions of E-cadherin, N-cadherin, Snail-1 and vimentin (P < 0.01).@*CONCLUSION@#CCN5 can regulate the proliferation, migration and invasion of HESCs and thus plays an important role in EMT of HESCs, suggesting the potential of CCN5 as a therapeutic target for endometriosis.

Effects of repetitive transcranial magnetic stimulation on sleep quality in patients with sleep disorder after stroke: systematic review and meta-analysis / 中国基层医药

Objective:To evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on sleep quality in patients with post-stroke sleep disorder (PSSD).Methods:The clinical randomized controlled trials involving PSSD patients who received rTMS were retrieved from nine medical databases. After excluding duplicated references, screening for independent references and risk evaluation, the remaining references were input into RevMan5.4 software for meta-analysis.Results:Twelve eligible literatures were included in the final analysis. Meta-analysis results revealed that after rTMS intervention, there were significant differences in the following terms between the treatment and control groups (all P < 0.05): Pittsburgh sleep quality index score [MD = -2.60, 95% CI (-3.03, -2.17), P < 0.000 01]; sleep latency [MD = -9.69, 95% CI (- 16.87, - 2.50), P < 0.01], sleep efficiency [MD = 8.90, 95% CI (5.41, 12.39), P < 0.01], number of awakenings [MD = -1.15, 95% CI (- 2.26, - 0.04), P = 0.04], awakening duration [MD = -10.95, 95% CI (- 13.30, -8.61), P < 0.01], and rapid eye movement [MD = 4.54, 95% CI (2.24, 6.85), P < 0.01] in polysomnography; brain-derived neurotrophic factor score [MD = 5.29, 95% CI (2.47, 8.11), P = 0.0002]; clinical curative rate [ OR = 4.46, 95% CI (2.75, 7.23), P < 0.000 01]. Conclusion:rTMS can improve the sleep quality in patients with PSSD, which is worthy of clinical promotion.

Analysis on Role of mTORC1/4E-BP1 Axis in Idiopathic Pulmonary Fibrosis and Research Progress of Bupleuri Radix on Its Intervention / 中国实验方剂学杂志

Idiopathic pulmonary fibrosis （IPF） is a common， lethal interstitial lung disease characterized by airway remodeling， inflammation， alveolar destruction， and fibrosis. The mammalian target of rapamycin complex 1/4E binding protein 1 （mTORC1/4E-BP1） axis is closely related to the expression of collagen by fibroblasts， and its role in pulmonary fibrosis remains to be further elucidated. Traditional Chinese medicine （TCM） has shown promising efficacy in improving the lung function， exercise capacity， and quality of life in patients with IPF. The theory of "same treatment for different diseases" provides a TCM theoretical basis for the treatment of pulmonary fibrosis with Bupleuri Radix， while the research in western medicine has preliminarily shown that both the formulation and single herb as well as the active ingredients of Bupleuri Radix have good therapeutic effects on pulmonary fibrosis. Therefore， this review will elaborate on the role of the mTORC1/4E-BP1 axis in the pathomechanism of IPF， as well as the research results of the active components of Bupleuri Radix on the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin protein（PI3K/AKT/mTOR） pathway， so as to provide a reference for the treatment and drug development of IPF.

Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.