Effect on Danggui Shaoyao Powder on mitophagy in rat model of Alzheimer's disease based on PINK1-Parkin pathway / 中国中药杂志

This study investigated the mechanism of Danggui Shaoyao Powder(DSP) against mitophagy in rat model of Alzheimer's disease(AD) induced by streptozotocin(STZ) based on PTEN induced putative kinase 1(PINK1)-Parkin signaling pathway. The AD rat model was established by injecting STZ into the lateral ventricle, and the rats were divided into normal group, model group, DSP low-dose group(12 g·kg~(-1)·d~(-1)), DSP medium-dose group(24 g·kg~(-1)·d~(-1)), and DSP high-dose group(36 g·kg~(-1)·d~(-1)). Morris water maze test was used to detect the learning and memory function of the rats, and transmission electron microscopy and immunofluorescence were employed to detect mitophagy. The protein expression levels of PINK1, Parkin, LC3BⅠ/LC3BⅡ, and p62 were assayed by Western blot. Compared with the normal group, the model group showed a significant decrease in the learning and memory function(P<0.01), reduced protein expression of PINK1 and Parkin(P<0.05), increased protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05), and decreased occurrence of mitophagy(P<0.01). Compared with the model group, the DSP medium-and high-dose groups notably improved the learning and memory ability of AD rats, which mainly manifested as shortened escape latency, leng-thened time in target quadrants and elevated number of crossing the platform(P<0.05 or P<0.01), remarkably activated mitophagy(P<0.05), up-regulated the protein expression of PINK1 and Parkin, and down-regulated the protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05 or P<0.01). These results demonstrated that DSP might promote mitophagy mediated by PINK1-Parkin pathway to remove damaged mitochondria and improve mitochondrial function, thereby exerting a neuroprotective effect.

Effects of Pearl Hydrolysate on Hepatic Sinusoidal Endothelial Cell Viability and Capillarization in Liver Fibrosis / 中国医学科学院学报

Objective To study the effect and mechanism of pearl hydrolysate on hepatic sinusoidal capillarization in liver fibrosis. Methods Hepatic sinusoidal endothelial cells (HSEC) and hepatic stellate cells (HSC-LX2) were incubated with Hepu pearl hydrolysate.The proliferation of HSEC and HSC-LX2 was examined by MTT colorimetry.The cell cycle and apoptosis of HSC-LX2 were measured by flow cytometry.The changes of the microstructures such as fenestra and basement membrane of HSEC were observed by transmission electron microscopy. Results The intervention with leptin increased the viability of HSC-LX2 (P=0.041),decreased the viability of HSEC (P=0.004),and caused capillarization signs such as decreased number and diameter of fenestrae and formation of continuous basement membrane.The treatment with pearl hydrolysate at different doses increased and expanded the fenestrae of HSEC (low dose:P=0.020;medium dose:P=0.028;high dose:P=0.032),disintegrated the extracellular basement membrane of HSEC (low dose:P=0.020;medium dose:P=0.028;high dose:P=0.032),decreased the viability of HSC-LX2 (low dose:P=0.018;medium dose:P=0.013;high dose:P=0.009),and induced the apoptosis of HSC-LX2 (low dose:P=0.012;medium dose:P=0.006;high dose:P=0.005).Pearl hydrolysate exerted therapeutic effect on capillarization in a dose-dependent manner (low dose:P=0.020;medium dose:P=0.028;high dose:P=0.032).Moreover,high-dose pearl hydrolysate showed stronger effect on capillarization of hepatic sinuses than colchicine (P=0.034) and salvianolic acid B (P=0.038). Conclusion Hepu pearl hydrolysate can increase the viability of HSEC,restore the area of fenestrae,disintegrate the basement membrane,and decrease the viability and induce the apoptosis of HSC-LX2,demonstrating significant pharmacological effects on the capillarization of HSEC and HSC-LX2.

Clinical Impact of Drug Adherence of Tyrosine Kinase Inhibitors in Children with Ph-Positive Acute Lymphoblastic Leukemia / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to explore the impact of ABL1–tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients’ prognosis from TKIs intake practices. @*Materials and Methods@#Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated. @*Results@#Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia. @*Conclusion@#TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.

Digoxin alleviates pulmonary fibrosis by regulating phosphatidylinositol-3-kinase/Akt signaling through inhibiting the activation of fibroblast: an in vivo and in vitro experiment / 中华危重病急救医学

Objective:To investigate the effect of digoxin on bleomycin-induced pulmonary fibrosis in mice, and investigate its possible mechanism through in vitro and in vivo experiments. Methods:① In vivo experiment: 60 C57/BL6J mice were randomly divided into control group, pulmonary fibrosis model group (model group), pirfenidone (300 mg/kg) group, digoxin 1.0 mg/kg and 0.2 mg/kg groups, with 12 mice in each group. The pulmonary fibrosis model of mice was reproduced by single intratracheal infusion of bleomycin (5 mg/kg). The control group was given the same amount of sterile normal saline. From the next day after modeling, each group was received corresponding drugs by intragastric administration once a day for 28 days. Control group and model group were given the same amount of normal saline. The mice were sacrificed and the lung tissue was collected to detect the lung coefficient. After hematoxylin-eosin (HE) and Masson staining, the lung tissue morphology and collagen changes were observed under light microscope. Immunohistochemistry was used to detect the positive expressions of α-smooth muscle actin (α-SMA) and extracellular matrix (ECM) collagen (COL-Ⅰ and COL-Ⅲ) in lung tissue. The protein expressions of ECM fibronectin (FN), transforming growth factor-β (TGF-β) and phosphorylation of Smad3 (p-Smad3) in lung tissue were detected by Western blotting. ② In vitro experiment: human embryonic lung fibroblast-1 (HFL-1) cells were cultured and divided into blank control group, fibroblast activation model group (model group), pirfenidone (2.5 mmol/L) group and digoxin 100 nmol/L and 50 nmol/L groups when cell density reached 70%-90%. After 3-hour treatment with corresponding drugs, except blank control group, the other groups were treated with TGF-β for 48 hours to establish fibroblast activation model. The expressions of α-SMA, FN and p-Smad3 proteins and the phosphorylations of phosphatidylinositol-3-kinase (PI3K)/Akt pathway proteins PI3K and Akt (p-PI3K, p-Akt) were detected by Western blotting. Results:① In vivo, compared with the control group, the alveolar structure of mice in the model group was significantly damaged, a large number of inflammatory cells infiltrated, collagen deposition in the lung interstitium was increased, the deposition of ECM in the lung tissue was also increased, and the expressions of α-SMA, FN, TGF-β and p-Smad3 protein were increased, indicating that the model of bleomycin-induced pulmonary fibrosis in mice was successfully prepared. Compared with the model group, digoxin significantly inhibited airway inflammation and collagen fiber deposition, reduced ECM deposition, and decreased the protein expressions of α-SMA, FN, TGF-β and p-Smad3, while the effect was better than that of the pirfenidone group, and the digoxin 1.0 mg/kg group had a better effect except FN [α-SMA ( A value): 5.37±1.10 vs. 9.51±1.66, TGF-β protein (TGF-β/GAPDH): 0.09±0.04 vs. 0.33±0.23, p-Smad3 protein (p-Smad3/GAPDH): 0.05±0.01 vs. 0.20±0.07, all P < 0.01]. ② In vitro, compared with the blank control group, the expressions of FN, α-SMA, p-Smad3 and PI3K/Akt signaling proteins in the model group were increased, indicating that the fibroblast activation model induced by TGF-β was successfully reproduced. Compared with the model group, digoxin significantly inhibited fibroblast activation, and decreased the expressions of FN, α-SMA, p-Smad3, and PI3K/Akt pathway proteins, moreover, the effect was better than that of the pirfenidone group, and decreased FN, SMA and p-Akt protein expressions were more obvious in digoxin 100 nmol/L group [FN protein (FN/GAPDH): 0.21±0.15 vs. 0.88±0.22, α-SMA protein (α-SMA/GAPDH): 0.20±0.01 vs. 0.50±0.08, p-Akt protein (p-Akt/GAPDH): 0.30±0.01 vs. 0.65±0.10, all P < 0.01]. Conclusion:Digoxin could suppress the pulmonary fibrosis in mice induced by bleomycin, which might be associated with the regulation of fibroblast activation via suppressing PI3K/Akt signaling pathway in a dose-dependent manner.

Prevalence of chronic respiratory symptoms and dyspnea and related factors in residents in China / 中华流行病学杂志

Objective: To understand the prevalence of chronic cough, chronic expectoration and dyspnea and related factors in residents aged ≥40 years in China, and provide basic data for the prevention and control of chronic respiratory diseases. Methods: Data were from 2014-2015 chronic obstructive pulmonary disease surveillance in China. The information about chronic respiratory symptoms were collected by face-to-face interview. The prevalence rates of chronic cough, chronic expectoration, dyspnea and chronic respiratory symptoms and their 95%CI were estimated with complex sampling weights. Results: A total of 75 082 subjects were included in the analysis. The prevalence rates of chronic cough, chronic expectoration, dyspnea and chronic respiratory symptoms in the Chinese aged ≥40 years were 3.75% (95%CI: 3.38%-4.11%), 5.83% (95%CI: 5.40%-6.26%), 2.45% (95%CI: 2.02%-2.87%) and 8.93% (95%CI: 8.25%-9.62%), respectively. The prevalence rates of chronic cough, chronic expectoration, dyspnea and chronic respiratory symptoms in patients with chronic respiratory diseases were relatively higher, which were 10.27%, 13.85%, 6.43%, 20.72% respectively. Multivariate logistic regression analysis showed that age, region, education level, occupation, BMI, family history of respiratory diseases, history of severe respiratory infections in childhood, exposure to dust or chemicals in workplace and smoking status affected the prevalence of chronic cough, chronic expectoration and dyspnea. The prevalence of the three types of chronic respiratory symptoms increased significantly with age, which were higher in western region, smokers and underweight/obese subjects. The three prevalence rates mentioned above were higher in those with a history of severe respiratory infection in childhood, those exposed to biomass fuel in household, and those exposed to dust or chemicals in workplace. Conclusions: The prevalence rate of chronic respiratory symptoms was high in residents aged ≥40 years in China. Many factors affected the prevalence of chronic respiratory symptoms. Comprehensive prevention and control measures targeting risk factors should be taken to reduce the burden of chronic respiratory diseases.

Baicalin inhibits LPS/IFN-γ-induced inflammation via TREM2/TLR4/NF-κB pathway in BV2 cells / 中国中药杂志

This study investigated the mechanism of baicalin on lipopolysaccharide(LPS)/interferon γ(IFN-γ)-induced inflammatory microglia based on the triggering receptor expressed on myeloid cells 2(TREM2)/Toll-like receptor 4(TLR4)/nuclear factor kappaB(NF-κB) pathway. Specifically, LPS and IFN-γ were used to induce inflammation in mouse microglia BV2 cells. Then the normal group, model group, low-dose(5 μmol·L~(-1)) baicalin group, medium-dose(10 μmol·L~(-1)) baicalin group, high-dose(20 μmol·L~(-1)) baicalin group, and minocycline(10 μmol·L~(-1)) group were designed. Cell viability was detected by CCK-8 assay and cell morphology was observed under bright field. The expression of interleukin-1β(IL-1β), interleukin-4(IL-4), inducible nitric oxide synthase(iNOS), interleukin-6(IL-6), interleukin-10(IL-10), and arginase-1(Arg-1) mRNA was detected by real-time quantitative PCR, the protein expression of tumor necrosis factor-α(TNF-α), IL-1β, TREM2, TLR4, inhibitor kappaB-alpha(IκBα), p-IκBα, NF-κB p65 and p-NF-κB p65 by Western blot, and transfer of NF-κB p65 from cytoplasm to nucleus by cellular immunofluorescence. Compared with the normal group, most of the BV2 cells in the model group tended to demonstrate the pro-inflammatory M1 amoeba morphology, and the model group showed significant increase in the mRNA levels of IL-1β, IL-6, and iNOS, decrease in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), rise of the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P<0.01), reduction in TREM2 protein expression, and increase in the expression of NF-κB p65 in nucleus. Compared with the model group, baicalin groups and minocycline group showed the recovery of BV2 cell morphology, significant decrease in the mRNA levels of IL-1β, IL-6 and iNOS, increase in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), reduction in the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P<0.05), rise of TREM2 protein expression, and decrease in the expression of NF-κB p65 in nucleus. In summary, these results suggest that baicalin can regulate the imbalance between TREM2 and TLR4 of microglia and inhibit the activation of downstream NF-κB, thus promoting the polarization of microglia from pro-inflammatory phenotype to anti-inflammatory phenotype.

Analysis of Neuroprotective Effect of Danggui Shaoyaosan on APPswe/PS1ΔE9 Transgenic Mice Based on Circular RNA Sequencing / 中国实验方剂学杂志

Objective:To investigate the neuroprotective effects of Danggui Shaoyaosan （DSS） on APP_swe/PS1_ΔE9transgenic （APP/PS1） mice and its mechanism related to circular RNA （circRNA）. Method:Totally twenty 6-month-old APP/PS1 mice were divided into model group and DSS group， and 10 C57BL/6 wild-type mice were set as the normal control group. The normal group and model group received the same volume of normal saline， and DSS group received drug by gavage administration， all for 8 weeks. The differentially expressed circRNA of APP/PS1 mice before and after DSS intervention was analyzed by circRNA sequencing to construct circRNA-miRNA mRNA interaction network. The results of cricRNA sequencing were then verified by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of phosphoinositide 3-kinase （PI3K）， p-PI3K， protein kinase B1 （Akt1）， p-Akt1， B lymphocytoma-2 （Bcl-2）， and Bcl-2-Associated X protein （Bax） in the hippocampus were detected by immunoblotting （Western blot）. The protein expression of Caspase-3 in the hippocampus was detected by immunohistochemistry and the level of apoptosis in the hippocampus was detected by the TUNEL method. Result:Compared with the model group， there were 90 differentially expressed circRNA after intervention with DSS， of which 46 were up-regulated and 44 down-regulated. Compared with the normal group， the expression levels of circRNA1398 and circRNA1399 in the model group decreased， and the expression levels of miR-103-3p， miR-153-3p， miR-143-3p， and miR-143-5p increased. Compared with the model group， the expression levels of circRNA1398 and circRNA1399 in the DSS group were up-regulated， while the expression levels of miR-103-3p， miR-153-3p， miR-143-3p， and miR-143-5p were down-regulated. Compared with the normal group， the expression of p-PI3K， Akt1， p-Akt1， and Bcl-2 in the model group decreased （<italic>P</italic><0.05，<italic> P</italic><0.01）， and the expression of Bax and Caspase in the model group increased （<italic>P</italic><0.01）. Compared with the model group， the expression of p-PI3K， Akt1， p-Akt1， and Bcl-2 in the hippocampus of the DSS group increased （<italic>P</italic><0.01）， and the protein expression of Bax and Caspase decreased （<italic>P</italic><0.01）. Compared with the normal group， the apoptosis level in the hippocampus of the model group increased， with an apoptosis rate of （43.76±2.92）%. Compared with the model group， the apoptosis rate of DSS group was （24.64±3.39）%. Conclusion:DSS can activate PI3K/Akt pathway and inhibit apoptosis in hippocampal neurons of APP / PS1 mice， and play a neuroprotective role. The specific mechanism may be related to the regulation of circRNA1398 and circRNA1399 expression and the corresponding miRNA expression.

Glycolysis reprogramming in cancer-associated fibroblasts promotes the growth of oral cancer through the lncRNA H19/miR-675-5p/PFKFB3 signaling pathway / 国际口腔科学杂志·英文版

As an important component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) secrete energy metabolites to supply energy for tumor progression. Abnormal regulation of long noncoding RNAs (lncRNAs) is thought to contribute to glucose metabolism, but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined. In the present study, by using RNA sequencing and bioinformatics analysis, we analyzed the lncRNA/mRNA profiles of normal fibroblasts (NFs) derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma (OSCC). LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs. Using small interfering RNA (siRNA) strategies, we determined that lncRNA H19 knockdown affected proliferation, migration, and glycolysis in oral CAFs. We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and miR-675-5p. Furthermore, the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs, as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor. Our study presents a new way to understand glucose metabolism in oral CAFs, theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.

Efficacy of Getong Tongluo Capsule () for Convalescent-Phase of Ischemic Stroke and Primary Hypertension: A Multicenter, Randomized, Double-Blind, Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension.@*METHODS@#This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed.@*RESULTS@#The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P0.05).@*CONCLUSION@#GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).

Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study / 中华医学杂志(英文版)

BACKGROUND@#Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.@*METHODS@#This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR.@*RESULTS@#A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.@*CONCLUSION@#Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients.@*CLINICAL TRIAL REGISTRATION@#ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.

Experience of Finland children's whole-course health care service and management and its enlightenment / 上海预防医学

Finland is acknowledged as an international leader in the children's health care by the World Health Organization, especially in the formulation and planning of children's health care policies. In the article, we introduces Finnish service mode and management experience in the whole-process medical care for children, including successful operation of hierarchical diagnosis and treatment, key role of public health nurses in the whole-process management, significant influence of social and family environment on the healthy development of children, and integration of children's health and welfare services through multi-sectoral cooperation. We make some suggestions and recommendations for the construction of children's health service capacity in China in strengthening the laws and policies in the children's health, improving the network construction and three-level connection of maternal and child health care system, taking the construction of pediatric integrated health care system as the breakthrough point to further promote hierarchical diagnosis and treatment, improving the multi-sectoral cooperation mechanism, and maximizing the influence of information technology and family.

Radiotherapy targeting cancer stem cells "awakens" them to induce tumour relapse and metastasis in oral cancer / 国际口腔科学杂志·英文版

Radiotherapy is one of the most common treatments for oral cancer. However, in the clinic, recurrence and metastasis of oral cancer occur after radiotherapy, and the underlying mechanism remains unclear. Cancer stem cells (CSCs), considered the "seeds" of cancer, have been confirmed to be in a quiescent state in most established tumours, with their innate radioresistance helping them survive more easily when exposed to radiation than differentiated cancer cells. There is increasing evidence that CSCs play an important role in recurrence and metastasis post-radiotherapy in many cancers. However, little is known about how oral CSCs cause tumour recurrence and metastasis post-radiotherapy. In this review article, we will first summarise methods for the identification of oral CSCs and then focus on the characteristics of a CSC subpopulation induced by radiation, hereafter referred to as "awakened" CSCs, to highlight their response to radiotherapy and potential role in tumour recurrence and metastasis post-radiotherapy as well as potential therapeutics targeting CSCs. In addition, we explore potential therapeutic strategies targeting these "awakened" CSCs to solve the serious clinical challenges of recurrence and metastasis in oral cancer after radiotherapy.

Pharmacological Evaluation for Extracts of Aconiti Radix and Aconiti Radix Cocta / 中国实验方剂学杂志

Objective: To carry out the studies of pharmacological action for extracts of Aconiti Radix and Aconiti Radix Cocta, and evaluate the selection of raw materials in prescriptions, in order to promote the development and clinical application of preparations. Method: The mixed extracts of Aconiti Radix and Aconiti Radix Cocta were prepared respectively according to the technique of aconitum injection, and different dose groups of Aconiti Radix and Aconiti Radix Cocta were established based on the dose of Aconiti Radix 0.152 5 mg·g-1, and then applied in such pharmacodynamic tests as analgesia, heart rate reduction, antitumor effect and toxicology tests, such as acute toxicity and organ observation. The data were analyzed systematically on the basis of literatures. Result: Compared with blank group, the extracts of both Aconiti Radix and Aconiti Radix Cocta had a significantly analgesic effect. At the same dose, the pain inhibition rate of Aconiti Radix injection (60.91%) was higher than that of Aconiti Radix Cocta injection (53.42%), and the pain inhibition rate of Aconiti Radix extract for oral administration(73.94%) was also much higher than that of Aconiti Radix Cocta extract (29.97%), with significant differences (Pth min after administration, the heart rate of the Aconiti Radix group was decreased first, then stabilized, and finally increased with the rise of the dose, while for the Aconiti Radix Cocta group showed a different trend of first stability, then decrease and finally increase. The result indicated the Aconiti Radix group had the effect in reducing heart rate in rats at a low dose. The survival inhibition rate was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The extracts of both Aconiti Radix and Aconiti Radix Cocta had a significantly inhibitory effect on the proliferation of AGS gastric cancer cells, in which Aconiti Radix was stronger than that of Aconiti Radix Cocta at the same dose. In the acute toxicity test of rats, lethal dose 50%(LD50) of Aconiti Radix and Aconiti Radix Cocta were 3.9 g·kg-1 and 21.0 g·kg-1 respectively, which were equivalent to 4 times and 20 times of the clinical dose. LD50 of the extract of Aconiti Radix Cocta was 5 times than that of Aconiti Radix. The liver and kidney of dead rats were dark with obvious symptoms of poisoning after dissection, while all the organs of rats at the clinical and lower dose were normal. Conclusion: The safety of Aconiti Radix is lower than that of Aconiti Radix Cocta, but with greater analgesic, bradycardic and anticancerous effect. Therefore, it is suggested that the preparations, such as aconitum injection, should be prepared with Aconiti Radix in the treatment of severe pain of patients with advanced gastric and liver cancer, and the preparations for general pain can be prepared with Aconiti Radix Cocta, so as to achieve a truly safe and effective dialectical treatment.

Effects of Benzoxazole Derivative PO- 296 on Dendritic Cell Differentiation and Related Indexes / 中国药房

OBJECTIVE： To investigate the effects of benzoxazole derivative 2-（chlorobenzoxazolyl-2-yl）-4，5，6，7-tetrahydro- dihydro-indazole-3-ol （PO-296） on the differentiation of murine bone marrow-derived dendritic cells（DC） and their related indexes as specific surface molecules and inflammatory cytokines. METHODS： Bone marrow nuclear cells of mice were isolated， and immature DC （imDC） was obtained by recombinant mice granulocyte macrophage colony-stimulating factor and recombinant mice IL-4. After pretreated with low-dose， medium-dose and high-dose （1， 5， 25 μmol/L） of PO-296， DC was obtained by lipopolysaccharide induction. Flow cytometry was used to detect the expression of DC specific surface molecules [i.e. the proportion of class Ⅱ major histocompatibility complex （MHC Ⅱ）， CD80， CD86 and chemokine receptor 7 （CCR7） positive cells]， imDC phagocytosis （i.e. the proportion of dextran positive cells） and DC survival （i.e. the proportion of survival cells）. ELISA method was used to detect the levels of inflammatory cytokines （IL-10， IL-12 and TNF-α） in cell culture medium. RESULTS： Compared with imDC group， the proportion of MHC Ⅱ， CD80 and CD86 positive cells were increased significantly in non-loading group （P＜0.05）. Compared with non-loading group， the levels of IL-10 in cell culture medium were increased significantly in PO-296 groups. The proportions of MHC Ⅱ， CD80 and CD86 positive cells in positive group and PO-296 medium-dose and high-dose groups as well as the levels of IL-12 and TNF-α in cell culture medium in administration groups were decreased significantly （P＜0.05）. There was no statistical significance in the proportion of CCR7 positive cells， dextran positive cells and survival cells in administration groups， compared with non-loading group （P＞0.05）. CONCLUSIONS： PO-296 has no obvious cytotoxicity and does not affect the phagocytic function of imDC. At the same time， the compound can inhibit the expression of DC specific surface molecules and regulate the secretion of inflammatory cytokines.

Modulation of mesenchymal stem cells on autophagy in hippocampus of rats with hypoxic-ischemic brain damage / 上海交通大学学报（医学版）

Objective·To investigate the effect of mesenchymal stem cells (MSCs) on autophagy in hippocampus of neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods·Western blotting was used to detect the expression levels of autophagy associated proteins Beclin1, LC3 Ⅱ , and p62 in the hippocampus of HIBD rats following MSCs transplantation and oxygen glucose deprivation (OGD)-injured primary neurons following MSCs seperated coculture. The learning-memory function in the HIBD rats after MSCs transplantation was tested by Morris water maze test. Transmission electron microscopy was also used to observe the number of autophagic neurons in OGD damaged neurons after coculture with MSCs. Results·The levels of Beclin1 and LC3 Ⅱ protein expressions were significantly increased at 12-24 h in the rat hippocampus following HIBD injury. MSCs transplantation statistically downregulated the autophagy level in the hippocampus, and obviously improved the learning-memory function of HIBD rats. Meanwhile, the levels of Beclin1 and LC3 Ⅱ protein expressions in the primary neurons in vitro were also induced by OGD for 12 h. MSCs seperated coculture significantly downregulated the autophagy level of hippocampal neurons by OGD injury, decreased the number of autophagosome in the OGD-injured neurons. Conclusion·MSCs may inhibit the autophagy of hippocampal neurons by partly regulating the damaged microenvironment to improve the learning and memory function of HIBD rats.

Paclitaxel coated balloon versus plain balloon angioplasty in treating popliteal arteriosclerosis occlusive disease / 中华普通外科杂志

Objective To compare the short-term clinical results of paclitaxel coated balloon angioplasty (PCBA) and plain balloon angioplasty (POBA) in remedying popliteal arteriosclerosis occlusive disease.Methods From July 2013 to July 2016,56 patients of severe intermittent claudication or critical limb ischemia (CLI) due to stenosis or occlusion of popliteal artery were treated by PCBA in 30 patients (30 limbs),and by POBA in 26 patients (26 limbs).We compared clinical data of both groups at 1,3 and 6 months.Results The mean(± SD)length of treated segment in PCBA and POBA group respectively was (8.6 ± 3.3) cm and (6.9 ± 3.7) cm (t =1.817,P ＞ 0.05).According to peak systolic velocity rate (PSVR ＞ 2.4 as restenosis),l-month,3-month and 6-month restenosis rates were 0 (0 patients)in PCBA group vs.11.5％ (3 patients)in POBA group(x2 =1.74,P ＞0.05),0(0 patients)vs.24.0％ (6 patients) (x2 =5.59,P ＜ 0.05),3.6％ (1 patients)vs.65.2％ (15 patients) (x2 =22.29,P ＜ 0.01),respectively.6-month target lesion revascularization(TLR) was 3.6％ (1 patient) in PCBA group vs.60.9％ (in 14 patients) in POBA group(x2 =19.97,P ＜0.01),limb salvage rate at 6 months was 100％ (28 patients)vs.65.2％ (15 patients) (x2 =11.55,P ＜ 0.01).Conclusion In the short term,paclitaxel coated balloon angioplasty was superior to POBA for anti-restenosis of popliteal arteriosclerosis occlusive disease.

Effect of dexmedetomidine combined with ropivacaine for ilioinguinal and iliohypogastric nerve block un-der sevoflurane anesthesia / 临床麻醉学杂志

Objective To investigate the clinical efficacy of dexmedetomidine combined with ropivacaine for ilioinguinal and iliohypogastric nerve block in elderly patients undergoing inguinal her-nia surgery.Methods Sixty elderly patients undergoing inguinal hernia surgery were randomly divided into dexmedetomidine group (group D)and control group (group C),30 patients in each group.All patients received ilioinguinal and iliohypogastric nerve block by the same anesthesiologist. 0.375% ropivacaine and dexmedetomidine 1 μg/kg 20 ml were used in ilioinguinal and iliohypogastric nerve block in group D,while 0.375% ropivacaine 20 ml were used in ilioinguinal and iliohypogastric nerve block in group C.Sensory block onset time and blockade duration were recorded.Side effects were recorded in both groups.Results Sensory block onset time in group D was significantly shorter than that in group C (10.6±4.3 min vs 14.4±5.1 min,P <0.05).Sensory block durations in group D was significantly longer than that in group C (832.7±136.6 min vs 669.8±140.1 min,P <0.05). There were two bradycardia cases in group D.No adverse reactions or anaesthesia complications oc-curred in all patients following postoperative follow-up.Conclusion Dexmedetomidine combined with ropivacaine can be used in ilioinguinal and iliohypogastric nerve block safely,and dexmedetomidine shortens the onset time and prolonged the duration of sensory block.

Perfusion of gastrodin in abdominal aorta for alleviating spinal cord ischemia reperfusion injury

OBJECTIVE@#To observe the effects of perfusion of the gastrodin in abdominal aorta for alleviating the spinal cord ischemia reperfusion injury (SCIRI).@*METHODS@#A total of 36 New Zealand white rabbits were divided randomly into sham-operated group (group S), control group (group C) and gastrodin group (group G), 12 rabbits for each group. Aorta abdominalis infrarenalis blocking method was applied to establish the SCIRI model. The changes of motor evoked potentials (MEPs) before the ischemia and on 30 min, 60 min, 6 h, 12 h and 24 h of reperfusion of the gastrodin were respectively recorded, and the neurologic function score before the ischemia, on the 6 h, 12 h and 24 h of the reperfusion of the gastrodin were assessed. And the changes of the concentration of serum neuron specific enolase (NSE), interleukin (IL)-lβ and IL-8 were measured before the ischemia, after 45 min of ischemia, and on 30 min, 60 min, 6 h, 12 h and 24 h of reperfusion of gastrodin. Then the levels of spinal cord nerve cells mitochondrial superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), total antioxidant capacity (T-AOC) and mitochondrial swelling degree (MSD) were tested and the histopathologic changes in spinal cord tissues were observed.@*RESULTS@#The levels of the NSE, IL-lβ, IL-8, ROS, MDA and MSD of group C were all significantly elevated after the ischemia (P < 0.01); the levels of the spinal nerve cell mitochondria SOD, GSH-PX and T-AOC were all significantly reduced (P < 0.01), MEPs and spinal cord tissue pathology were damaged significantly (P < 0.01). The rate of motor neuron abnormalities and the damages of spinal cord tissue pathology of group G were significantly milder than those of group C (P < 0.01); the levels of NSE, IL-lβ, IL-8, ROS, MDA and MSD were significantly lower than those of group C (P < 0.01), but the levels of SOD, GSH-PX and T-AOC were all significantly higher than those of group C (P < 0.01), and the recovery of neurologic function score during the reperfusion of gastrodin was significantly faster than group C (P < 0.01).@*CONCLUSIONS@#Perfusion of the gastrodin in abdominal aorta can alleviate the spinal cord ischemia reperfusion injury by promoting the mitochondrial antioxidant capacity and inhibiting the inflammatory reaction.

Perfusion of gastrodin in abdominal aorta for alleviating spinal cord ischemia reperfusion injury

Objective To observe the effects of perfusion of the gastrodin in abdominal aorta for alleviating the spinal cord ischemia reperfusion injury (SCIRI). Methods A total of 36 New Zealand white rabbits were divided randomly into sham-operated group (group S), control group (group C) and gastrodin group (group G), 12 rabbits for each group. Aorta abdominalis infrarenalis blocking method was applied to establish the SCIRI model. The changes of motor evoked potentials (MEPs) before the ischemia and on 30 min, 60 min, 6 h, 12 h and 24 h of reperfusion of the gastrodin were respectively recorded, and the neurologic function score before the ischemia, on the 6 h, 12 h and 24 h of the reperfusion of the gastrodin were assessed. And the changes of the concentration of serum neuron specific enolase (NSE), interleukin (IL)-lβ and IL-8 were measured before the ischemia, after 45 min of ischemia, and on 30 min, 60 min, 6 h, 12 h and 24 h of reperfusion of gastrodin. Then the levels of spinal cord nerve cells mitochondrial superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), total antioxidant capacity (T-AOC) and mitochondrial swelling degree (MSD) were tested and the histopathologic changes in spinal cord tissues were observed. Results The levels of the NSE, IL-lβ, IL-8, ROS, MDA and MSD of group C were all significantly elevated after the ischemia (P < 0.01); the levels of the spinal nerve cell mitochondria SOD, GSH-PX and T-AOC were all significantly reduced (P < 0.01), MEPs and spinal cord tissue pathology were damaged significantly (P < 0.01). The rate of motor neuron abnormalities and the damages of spinal cord tissue pathology of group G were significantly milder than those of group C (P < 0.01); the levels of NSE, IL-lβ, IL-8, ROS, MDA and MSD were significantly lower than those of group C (P < 0.01), but the levels of SOD, GSH-PX and T-AOC were all significantly higher than those of group C (P < 0.01), and the recovery of neurologic function score during the reperfusion of gastrodin was significantly faster than group C (P < 0.01). Conclusions Perfusion of the gastrodin in abdominal aorta can alleviate the spinal cord ischemia reperfusion injury by promoting the mitochondrial antioxidant capacity and inhibiting the inflammatory reaction.

Energy Balance-related Behaviors Are Related to Cardiometabolic Parameters and Predict Adiposity in 8-14-year-old Overweight Chinese Children One Year Later / 生物医学与环境科学（英文）

To identify target energy balance-related behaviors (ERBs), baseline data from 141 overweight or obese schoolchildren (aged 8-14 years old) was used to predict adiposity [body mass index (BMI) and fat percentage] one year later. The ERBs included a modified Dietary Approach to Stop Hypertension diet score (DASH score), leisure-time physical activity (PA, days/week), and leisure screen time (minutes/day). Several cardiometabolic variables were measured in the fasting state, including systolic blood pressure (SBP), diastolic blood pressure (DBP), blood glucose (GLU), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C). BMI and fat percentage were measured using a BIA body composition analyzer (MC-980MA, TANITA, Tanita Co., Guangzhou, China). Partial correlation coefficients (partial r) and multiple linear regression models were used to predict BMI and fat percentage one year later. Our sample consisted of 114 boys and 83 girls with a mean BMI of 24.7±3.7 kg/m2 and fat percentage of 34.2%±8.3% at baseline. BMI, fat percentage, and certain cardiometabolic variables were negatively associated with DASH score and leisure-time PA (all P<0.05), but positively associated with leisure screen time (all P<0.05) at baseline. Statistically significant predictors of BMI and fat percentage one year later were baseline BMI (partial r=0.85), fat percentage (partial r=0.69), eating out (times/week, partial r=0.18), and DASH Score (partial r=-0.18). Overall, childhood obesity prevention interventions should target reductions in ERBs.