Mechanism of Quercetin in Protecting Articular Cartilage from Osteoarthritis Based on p38 MAPK Pathway / 中国实验方剂学杂志

Objective:To investigate the protective effect of quercetin （Qu） on articular cartilage of knee osteoarthritis and its mechanism by inhibiting p38 mitogen activated protein kinase （MAPK） signaling pathway. Method:Through the network pharmacology technology，we scientifically predicted and analyzed the target factors and signal pathways of Qu in the protection of articular cartilage in patients with osteoarthritis. We selected a prediction pathway closely related to osteoarthritis and validated it by cell experiment <italic>in vitro</italic>. The best intervention concentration of the drug was selected by cell counting kit-8 （CCK-8） method. The osteoarthritis and its closely related inflammatory factors interleukin（IL）-1<italic>β</italic> and tumor necrosis factor（TNF）-<italic>α</italic> were detected by enzyme linked immunosorbent assay（ELISA）. The expression of related mRNA and protein in p38 signal pathway after Qu intervention were detected by quantitative real time polymerase chain reaction（Real-time PCR） and Western blot. Result:It was predicted that MAPK signal pathway was closely related to osteoarthritis by network pharmacology，and p38 MAPK pathway，which was most closely related to osteoarthritis，was selected for study. The results showed that 100 μmol·L^-1 Qu had the most obvious effect in decreasing the expression of related inflammatory factors，inhibited the expression of p38，phosphorylated（p）-p38，matrix metalloproteinase-13（MMP-13），A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs-4（ADAMTS-4） in the pathway，and promoted the expression of CollagenⅡ. Conclusion:Qu could decrease the expression of cartilage inflammatory factors in the prevention and treatment of osteoarthritis，and the effect can be well developed by intervening and inhibiting p38 MAPK pathway related factor expression level. All the results show that Qu can decrease osteoarthritis inflammatory factors and protect articular cartilage in patients with osteoarthritis.

Identification of quality markers of Qixuehe Capsules based on analytic hierarchy process and entropy weight methods / 中国中药杂志

Qixuehe Capsules is a compound Chinese patent medicine developed for treating the disorder of Qi and blood(a common etiology of gynecological disease), which has remarkable effects on smoothing liver and regulating Qi, activating blood circulation, and relieving pain. However, due to its complex prescriptions(15 herbs) and multiple effects, the quality control of Qixuehe Capsules has always been a bottleneck problem limiting its sustainable development. Therefore, this study adopted the traditional Chinese medicine Q-markers quantitative identification system established previously by our research group based on the combination of analytic hierarchy process and entropy weight methods. With the different effects of Qixuehe Capsules as the entry point, the comprehensive scores of chemical ingre-dients in Qixuehe Capsules under the items of effectiveness(smoothing liver and regulating qi, activating blood circulation, and relieving pain), testability and specificity were calculated and integrated, respectively. Subsequently, through the analysis of compatibility relationship of Qixuehe Capsules, 15 active ingredients with high comprehensive scores were found to be the top Q-mar-kers of Qixuehe Capsules, including ferulic acid, quercetin, caffeic acid, kaempferol, rutin, Z-ligustilide, senkyunolide Ⅰ, vanillic acid, protocatechuic acid, chlorogenic acid, rosmarinic acid, senkyunolide A, gallic acid, tetrahydropalmatine and eugenol. Collectively, this study not only provided scientific evidence for further research on the improvement and standardization of quality standards of Qixuehe Capsules but also provided methodological references for the quantitative identification of Q-markers of multi-effect traditional Chinese medicine formulae.

Association between Self-reported Snoring and Prediabetes among Adults Aged 40 Years and Older without Diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Several previous studies have shown that snoring is associated with glucose metabolism and the development of diabetes, but rare study has shown the association between snoring frequency and prediabetes, particularly in China. We hypothesized that individuals who snore might have a higher risk of prediabetes. This study aimed to investigate the association between self-reported snoring and prediabetes in a Chinese population.</p><p><b>METHODS</b>A cross-sectional study was performed in three large communities of Beijing from December 2011 to August 2012 by recruiting individuals aged ≥40 years old. All participants were requested to complete a detailed questionnaire and undergo anthropometric measurements. A 75 g oral glucose tolerance test was performed in individuals without diabetes. Blood samples of all participants were collected; blood glucose and blood fat levels were measured. Multivariate logistic regression models were built to assess the association between snoring frequency and prediabetes.</p><p><b>RESULTS</b>A total of 13,592 participants (female: 66.56%; mean age: 56.8 ± 7.9 years; mean body mass index: 25.5 ± 3.4 kg/m2) were included in the final analysis. Of these, 30.9% were diagnosed with prediabetes, while 41.3% and 25.4% had occasional and habitual snoring, respectively. Habitual snoring was associated with an increased risk of prediabetes (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 1.1-1.4, P< 0.001), after adjusting for diabetes and sleep-related confounders in the multivariable models. Habitual snoring was also associated with isolated impaired fasting glucose (IFG; OR: 1.3, 95% CI: 1.0-1.6; P< 0.001) and isolated impaired glucose tolerance (IGT; OR: 1.3, 95% CI: 1.2-1.5; P< 0.001), but not IFG + IGT (OR: 1.1, 95% CI: 0.9-1.4; P = 0.281). When stratified by total cholesterol (TC) levels, this association between habitual snoring and prediabetes was observed only in individuals with TC <5.6 mmol/L (OR: 1.4, 95% CI: 1.2-1.6; P< 0.001).</p><p><b>CONCLUSIONS</b>Habitual snoring is associated with prediabetes, but only in individuals with TC <5.6 mmol/L. Further prospective studies are needed to confirm this finding.</p>

Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Prolonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism (IHH) may produce adverse effects on the endocrine homeostasis and metabolism. This study aimed to compare basal serum adrenocorticotropic hormone (ACTH) and cortisol levels between male IHH patients and healthy controls. Moreover, this study compared the basal hypothalamic-pituitary-adrenal (HPA) axis in patients with and without nonalcoholic fatty liver disease (NAFLD), and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients.</p><p><b>METHODS</b>This was a retrospective case-control study involving 75 Chinese male IHH patients (mean age 21.4 ± 3.8 years, range 17-30 years) and 135 healthy controls after matching for gender and age. All subjects underwent physical examination and blood testing for serum testosterone, luteinizing hormone, follicle-stimulating hormone, ACTH, and cortisol and biochemical tests.</p><p><b>RESULTS</b>Higher basal serum ACTH levels (8.25 ± 3.78 pmol/L vs. 6.97 ± 2.81 pmol/L) and lower cortisol levels (366.70 ± 142.48 nmol/L vs. 452.82 ± 141.53 nmol/L) were observed in male IHH patients than healthy subjects (all p<0.05). IHH patients also showed higher metabolism parameters and higher prevalence rate of NAFLD (34.9% vs. 4.4%) than the controls (all P < 0.05). Basal serum ACTH (9.91 ± 4.98 pmol/L vs. 7.60 ± 2.96 pmol/L) and dehydroepiandrosterone sulfate (2123.7 ± 925.8 μg/L vs. 1417.1 ± 498.4 μg/L) levels were significantly higher in IHH patients with NAFLD than those without NAFLD (all P < 0.05). We also found that basal serum ACTH levels were positively correlated with NAFLD (r = 0.289,p<0.05) and triglyceride levels (r = 0.268, P< 0.05) in male IHH patients. Furthermore, NAFLD was independently associated with ACTH levels in male IHH patients by multiple linear regression analysis.</p><p><b>CONCLUSIONS</b>The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls. NAFLD was an independent associated factor for ACTH levels in male IHH patients. These preliminary findings provided evidence of the relationship between basal serum ACTH and NAFLD in male IHH patients.</p>

MRI diagnosis of Joubert syndrome and its differential diagnosis / 中华神经医学杂志

Objective To study the clinical and MR imaging features of patients with Joubert syndrome to improve the understanding of this disorder and the diagnosis accuracy.Methods A retrospective study of clinical and MR imaging data was performed in 3 pediatric patients had definite diagnosis of Joubert syndrome; and a comprehensive review of literature was presented.Results All 3 patients showed typical manifestations of complex brainstem malformations on MR imaging which comprised the "molar tooth sign" on midbrain level,"thin median cleft" separating cerebellar hemispheres and "bat wing" appearance of the fourth ventricle due to the cerebellar vermis hypoplasia.Clinically,hypotonia,intermittent irregular breathing pattern (with apnea in 1 patient) and developmental delay/mental retardation in infancy in all 3 patients and abnormal eye movements (episodic deviation to lateral extremes of gaze) in 1 patient were noted.Conclusion Joubert syndrome is characterized on MR imaging,but clinical data is necessary for an exact diagnosis; differentiation should be made with the other disorders due to the hypoplasia of cerebellar vermis.

Analysis on pathogen detection for 53 influenza outbreaks / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>In order to provide a scientific basis for influenza prevention and control, analyzing the epidemic characteristics and laws of influenza outbreaks in Xuzhou area during 2005-2011.</p><p><b>METHOD</b>Using fluorescent-PCR method to detect influenza virus nucleic acid on Nasopharyngeal swab specimens collected from influenza outbreak cases during 2005-2011 and fast classifying influenza virus A1 (H1N1), A3 (H3N2), new H1N1 BV (Victoria) and BY (Yamagate) on subtypes. At the same time, isolating the influenza virus with MDCK cells, and sending them to the National Influenza Center for review, after the preliminary identification of the isolated influenza virus.</p><p><b>RESULTS</b>During 2005-2011, there are 53 influenza outbreaks in Xuzhou area, which caused by influenza virus subtype BV accounting for 26.42% (14/53), A3 accounting for 49.1% (26/53), A3 and A1 mixture accounting for 3.77% (2/53) and the new H1N1 accounting for 20.75% (11/53). The outbreaks in 2007 and 2009 mainly caused by A3, and show that the winter spring (January) and summer autumn (September) as two popular peaks during 2005-2011; BV mainly causes the outbreaks from Feb. to Jun.</p><p><b>CONCLUSION</b>In Xuzhou area, since the winter of 2005, influenza virus subtype BV, the A3, and new H1N1 has alternately as mainly predominant strain, caused local influenza outbreaks. In which BV has increased trend year by year during 2005-2011. The students in primary and secondary schools are the major crowd of influenza outbreaks. Fluorescent-PCR detection methods could be a preferred method for reliable and rapid diagnostic of epidemic influenza outbreaks.</p>

Etiological analysis of influenza surveillance data in Xuzhou from 2005 to 2011 / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence and subtypes of influenza viruses in Xuzhou city from 2005 to 2011 and to provide the scientific supports for influenza prevention and control in this religion.</p><p><b>METHODS</b>The throat swab samples were collected from the influenza-like cases from national influenza like illness sentinel hospital in Xuzhou. The samples were used for influenza virus isolation and identification, sent on the national flu center to confirm according to the "national influenza surveillance program" and "influenza virus and experimental technology".</p><p><b>RESULTS</b>From Oct. 2005 to Dec. 2011, a total of 9561 swab specimens were collected in which 1152 strains were identified for influenza viruses with total isolated rate of 12.0%. Among these strains, 708 strains were A1 (H1N1) subtype (14.2%), 466 strains were A3 (H3N2) subtype (40.5%), 78 strains were new H1N1 subtype (6.8%), 362 strains were BV (Victoia) subtype (31.4%) and 82 strains were BY (Yamagate) subtype (7.1%). The top detection rate (25.9%) arose in 2007, secondary detection rate (17.4%) occurred at 2009 and the lowest one (2.3%) appeared in 2011. From the winter of 2005 to the spring of 2006 A1 (H1N1) subtype had appeared as predominant strains but in the winter of 2006 the predominant strains were BV subtype. It changed to A3 subtype in 2007 to 2009 and the other three dominant strains were A1, BV and BY in 2008. In the winter of 2009, both A3 (H3N2) and new H1N1 subtype were predominant strains. BV subtype was predominant strains in 2010 to 2011. The prevalence of A3 subtype appeared in all the year while prevalence of BV only arose in the spring and winter. So the detection rate was high in January (34.4%) but low in August (2.2%). The influenza population is correlated with age, the highest detection rate arose in 5-age group and the lowest detection rate appeared in 25-age group.</p><p><b>CONCLUSION</b>Influenza subtype A1, A3, New H1N1 are all appeared as predominant strains in Xuzhou city from 2005 to 2010. Besides, the prevalence of BV subtype is stronger in recently.</p>

Immunotherapy effect of dendritic cells pulsed by lysate of tumor cell Ar-He cryoablation on rat models of intracraniai gliomas / 中华神经医学杂志

Objective To investigate the role of C6 glioma cells mediated by rapid freezing and thawing ofAr-He cryoablation in the maturation of marrow-derived dendritic cells (BM-DCs) in Wistar rats,and the anti-tumor effect of these DCs on rat models of intracranial gliomas. Methods C6 glioma cells were routinely cultured in vitro; rapid freezing and thawing of Ar-He cryoablation was employed in C6 glioma cells of the experimental group, and C6 glioma cells of the negative control group were only performed insertion of the probe; blank control group (using rapid freezing and thawing of Ar-He cryoablation on the same amount of PBS) was also employed.Bone marrow-derived mononuclear cells (MNCs) were first prepared from tibia and femur bones of Wistar rats. These cells were cultured with such cytokines as recombinant granulocyte-macrophage colony-stimulating factor (rmGM-CSF),recombinant interleukin-4 (rmIL-4) and tumor necrosis factor-alpha (TNFα) to induce their maturation; BM-DCs were pulsed with or without tumor cell lysate obtained by rapid freezing and thawing of Ar-Hecryoablation at a ratio of (DC:tumor cells =1:3) 7 d after that.Morphological observation of BM-DCs was performed by light microscopy and the expression of DCs costimulatory molecules CD80 and CD86 were measured by flow cytometry 48 h after the addiction; the IL-12 level in the supematant of DCs was detected by ELISA. In order to determine whether or not vaccination with C6 TP DCs can induce the therapeutic potential in the established glioma-bearing models, the C6 cells cultured in vitro were stereotaxically implanted into the left caudate nucleus of Wistar rat brain; glioma-bearing rats were injected with vaccination with DCs,cells from the blank control group and negative control group on the 3rd and 10th d. Survival time was observed and determined using the method of Kaplan-Meier and Log-Rank analysis. Results DCs from rats' bone marrow cells cultured with cytokines and pulsed with tumor lysates showed the characters of typical mature DCs.Morphologically,these cells were large with oval or irregularly shaped nuclei and with many small dendrites. Phenotypically, they expressed high levels of CD80 and CD86 antigens (71.8 1％± 1.10％ and 74.66％± 1.48％ in experimental group,49.49％±1.08％ and 51.20％±2.06％ in negative control group, and 48.47％±1.09％ and 49.53％±1.89％ in blank control group); significant difference was noted between each 2 groups (P＜0.05).Functionally,the IL-12level in the supernatant of DCs showed obvious increment in the experimental group (245.99 ±3.20pg/mL) as compared with that in the negative control group (138.68±3.20 pg/mL) and blank control group (135.16±2.88 pg/mL,P＜0.05).These cells gained the capacity of mediating immunotherapy against intracranial gliomas in rats:the median survival in the experimental group (33 d) was significantly higher than that in the negative control and blank control groups (22 and 24 d, respectively, P＜0.05).Conclusion C6 glioma cells mediated by rapid freezing and thawing of Ar-He cryoablation can induce maturation of BM-DCs in Wistar rats; these BM-DCs pulsed with tumor lysates, as new therapeutic vaccines,can mediate immunotherapy against intracranial gliomas in rats.

Research on the aetiology of suspected enterovirus infected patients in Xuzhou district in 2009 / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To understand and master the situation in which enterovirus caused hand-foot-and-mouth disease (HFMD) in Xuzhou district in 2009 so as to provide scientific basis for the control and prevention of hand-foot-and-mouth disease.</p><p><b>METHODS</b>The researchers adopted fluorescence RT-PCR method to detect EV and EV71 as well as the CA16 specificity RNA from 222 samples of anal swabs and oropharyngeal swabs from the 240 cases who were diagnosed clinically as hand-foot-mouth disease infected by enterovirus. Also, the researchers conducted EV71-IgM antibody detection on 114 samples of acute phase serum with ELA method.</p><p><b>RESULTS</b>Among the 240 enterovirus infected patients, the total EV infection rate is 72.50% (174/240), among which EV71 infection rate is 57.92% (139/240), CoxA16 infection rate is 9.17% (22/240), and other EV infection rate is 5.42% (13/240). The EV71-RNA positive rate of the samples of 222 anus swabs among the 240 suspected enterovirus infected patients is 45.94% (102/222), the samples of swallow swab EV71-RNA positive rate is 25.68% (57/222) and the EV71-IgM antibody positive rate of 114 samples of acute phase serum is 86.84% (99/114). The EV71-RNA positive rate of oropharyngeal swabs of 254 healthy children is 1.57% (4/254) , and no CoxA16-RNA was detected. In the oropharyngeal swabs of 54 close contacts (medical personnel), the EV-RNA detected is negative. The positive rate of EV71-IgM antibody of the 258 healthy children's serum samples is 2.71% (7/258).</p><p><b>CONCLUSION</b>The widespreading of hand-foot-mouth disease in Xuzhou district is caused mainly by type 71 enterovirus. Inapparent infection of type 71 enterovirus exists among children under the age of 3 during the time of widespreading period and IgM antibody develops in them. It is difficult for adults to be infected by EV71 even if they contact the contagion source closely. The positive rate of EV71-IgM antibody in the samples of acute phase serum of suspected cases is the highest (86.84%), and the second highest is the positive rate of RNA of EV71 of anal swabs (45.94%) and of the EV71 of oropharyngeal swabs (25.68%). ELA reagent kit is used in the early diagnosis of EV71 infection for it is easy to operate, fast and economic, so, it is worth popularizing in the grass-root medical units.</p>

Rapid pore cranial drilling and ventricular drainage treatment in ventricular hemorrhage: a clinical analysis of 3571 cases / 中华神经医学杂志

Objective To summarize the clinical effects and experiences of rapid pore cranial drilling and ventricular drainage treatment on ventricular hemorrhage to evaluate the performance of rapid pore cranial drilling. Methods The clinical data of 3571 patients with ventricular hemorrhage performed the rapid pore cranial drilling and ventricular drainage treatment from 13 hospitals of Shandong province since 1977 were retrospectively analyzed and concluded; these data were compared with those in patients received traditional Dandy's device. Results In these 3571 patients, the cure rate was 27.1%, the improvement rate was 49.1%, and the death rate was 23.8%. Rapid pore drilling needed no scalp incision, no suction, no coagulation, or no special lighting, only needed puncturing the scalp, drilling through the cranium and dura matter, implanting drainage tube and stitching it up; one can manage it in about 5 minutes at bedside; while the traditional Dandy's drilling occupied 3 people in the operating room, needed more than 20 procedures, and plus the time transporting the patient, it needed at least 60 minutes or more to finfish the procedures. Rapid pore cranial drill device is superior to Dandy's cranial drill device in operating procedures, technical performance, operation conditions, personnel and time-consuming. Conclusion Rapid pore cranial drilling greatly simplifies the operating procedures, saves precious time for the seriously ill patients, reduces the mortality and improves the effectiveness of the treatment. After 35 years of clinical practice, to those patients seriously ill needed ventricular drainage treatment to rescue their lives, rapid pore cranial drilling is superior to traditional Dandy's drill technic, and is an effective method treating such diseases.

Effects of tributyltin chloride (TBT) and triphenyltin chloride (TPT) on rat testicular Leydig cells / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of tributyltin chloride (TBT) and triphenyltin chloride (TPT) on rat testicular Leydig cells.</p><p><b>METHODS</b>The rat Leydig cells (LC-540) were incubated with 0 to 80 nmol/L TBT and TPT for 24 to approximately 96 h, and then the cell viability was determined by MTT. DNA fragmentation ladder formation of cell apoptosis was examined by agarose electrophoresis. Effects of chelator of intracellular Ca2+ (BAPTA) and the inhibitors of PKA, PKC and TPK on cell apoptosis induced by TBT were observed. Effects of TBT on testosterone production in primary cultured rat Leydig cells treated with or without hCG were detected.</p><p><b>RESULTS</b>TBT and TPT suppressed Leydig cell survival in a time- and dose-dependent manner. The suppressive effects of TBT and TPT on the cell survival was caused by apoptosis which was determined by DNA ladder formation. The apoptotic effect of TBT was possibly mediated by the rise in intracellular Ca2+ because it could be blocked by BAPTA, the chelator of intracellular Ca2+; PKA, PKC and TPK inhibitors did not prevent the apoptotic effects induced by TBT. TBT markedly suppressed testosterone production of primary cultured rat Leydig cells with or without hCG stimulation.</p><p><b>CONCLUSION</b>TBT and TPT induced apoptosis in rat testicular Leydig cells possibly through increasing intracellular Ca2+. TBT reduced the testosterone production of rat Leydig cells.</p>

Establishment of drug-resistance cell line of human glioma mediated by MGMT / 中国医学科学院学报

<p><b>OBJECTIVE</b>To establish a drug-resistance cell line of human glioma mediated by MGMT.</p><p><b>METHODS</b>Simulated the clinical usage of BCNU to establish a BCNU-resistant human glioma subline by cyclic exposing the U251 parent cells to a constant concentration of BCNU. The resistance index and the expression of MGMT mRNA of U251/BCNU were detected and compared the difference of in vitro proliferation between U251 and U251/BCNU.</p><p><b>RESULTS</b>A subline--U251/BCNU was successfully established in about 4-month culture, which had a stable resistance to BCNU. U251/BCNU cells showed 17-fold higher resistance to BCNU than did U251 cells by MTT assay, while U251/BCNU cells expressed MGMT mRNA. The doubling time of U251 and U251/BCNU had no statistical difference.</p><p><b>CONCLUSION</b>A drug-resistance cell line of human glioma mediated by MGMT is established, which could provide experimental basis for further studies on the resistance mechanism and reversal methods of glioma chemotherapy.</p>

Emodin stimulates glucose uptake by HepG2 hepatocyte through activation of PPAR? / 中华内分泌代谢杂志

Objective To construct PPAR?and PPAR?response element (PPRE)-controlled luciferase expression vectors,and to determine whether the traditional Chinese medicine emodin activates PPAR?and improves the glucose uptake by HepG2 hepatocytes.Methods (1) PPAR?and PPRE luciferase expression vectors were constructed and were applied to screen more than 20 ingredients of the traditional Chinese medicine. (2) HepG2 cells were incubated with emodin which can activate PPAR?and PPRE luciferase activity,and the PPAR?mRNA expression level was evaluated by RT-PCR/Southern blot.(3) PPAR?and glucose transporter 2 (Glut2) proteins were determined by Western blot analysis in HepG2 cells treated with emodin.(4) The glucose uptake rate was measured using 2-deoxy-[~3H]-D-glucose in HepG2 cells after treatment with emodin.Results (1) Emodin stimulated luciferase activity controlled by PPRE in dose-dependent manner at concentrations of 0.04 to 180?mol/L in COS-7 cells.The highest value was about 4 folds of control in the cells treated with 90?mol/L emodin (P