Bacteroides thetaiotaomicron and its inactivated bacteria ameliorate colitis by inhibiting macrophage activation.

BACKGROUND: Studies have demonstrated that Bacteroides thetaiotaomicron (BT) has protective effect against colon inflammation in murine models. Macrophages play an important role in gut immunity. However, the specific mechanisms of BT on macrophage are still unelucidated. Thus, our study investigates the anti-inflammatory effect of BT and its heat-treated inactivated bacteria on experimental colitis and macrophages. METHODS: A dextran sulfate sodium (DSS)-induced acute colitis model with male C57BL/6 mice, BT (ATCC29148) strain, THP1 cell lines were used in this study. Live and heat-treated inactivated BT (IBT) solution (1 × 10^9cfu/ml) were intragastrically gavaged daily for 14 days. Colonic inflammation was determined by the disease activity index (DAI) score, colon length, histological score, and inflammatory factors. THP1 cells were induced towards M1, then treated with different concentrations of inactivated BT solution and p38 inhibitor. Western blotting, immunohistochemistry, immunofluorescence and qRT-PCR were performed to assess the levels of inflammatory cytokines and molecules of MAPK pathway including IL-6, TNF-α, IL-1ß, IL-22, p38 and phosphor-p38 expressions. Moreover, 16S rRNA sequencing of colitis murine fecal samples was applied to investigate the influence of supplementation of BT to the gut microbiota homeostasis. RESULTS: Both live and heat-treated inactivated BT decreased the DAI and histological scores as well as levels of inflammatory factors, particularly IL-6 while increasing IL-22 of DSS-induced colitis murine models. The cell experiments showed that inactivated BT downregulates IL-6 expression in THP1 via inhibiting p38 phosphorylation and affecting M1 polarization. Moreover, the 16S rRNA sequencing results showed that BT and IBT gavage could increase beta-diversity of gut flora in DSS-induced colitis mice. Furthermore, the significance test for differences between the groups showed that BT could increase Faecalebaculum, Lactobacillus and Bacteroides, while decreasing Akkermansia. CONCLUSION: In summary, our findings imply that BT and its heat-treated inactivated bacteria exert a protective effect by suppressing macrophage-induced IL-6 through the inhibition of p38 MAPK pathway and ameliorating intestinal gut dysbiosis in experimental colitis.

Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial / 中华心血管病杂志

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.

Epigenetic drug library screening reveals targeting DOT1L abrogates NAD+synthesis by reprogramming H3K79 methylation in uveal melanoma / 药物分析学报

Uveal melanoma(UM)is the most frequent and life-threatening ocular malignancy in adults.Aberrant histone methylation contributes to the abnormal transcriptome during oncogenesis.However,a comprehensive understanding of histone methylation patterns and their therapeutic potential in UM remains enigmatic.Herein,using a systematic epi-drug screening and a high-throughput transcriptome profiling of histone methylation modifiers,we observed that disruptor of telomeric silencing-1-like(DOT1L),a methyltransferase of histone H3 lysine 79(H3K79),was activated in UM,especially in the high-risk group.Concordantly,a systematic epi-drug library screening revealed that DOT1 L inhibitors exhibited salient tumor-selective inhibitory effects on UM cells,both in vitro and in vivo.Combining Cleavage Under Targets and Tagmentation(CUT&Tag),RNA sequencing(RNA-seq),and bioinformatics analysis,we identified that DOT1 L facilitated H3K79 methylation of nicotinate phosphoribosyltransferase(NAPRT)and epigenetically activated its expression.Importantly,NAPRT served as an oncogenic accel-erator by enhancing nicotinamide adenine dinucleotide(NAD+)synthesis.Therapeutically,DOT1L inhi-bition epigenetically silenced NAPRT expression through the diminishment of dimethylation of H3K79(H3K79me2)in the NAPRT promoter,thereby inhibiting the malignant behaviors of UM.Conclusively,our findings delineated an integrated picture of the histone methylation landscape in UM and unveiled a novel DOT1L/NAPRT oncogenic mechanism that bridges transcriptional addiction and metabolic reprogramming.

Advances in pharmacological effects of jujuboside B / 中国中药杂志

Ziziphi Spinosae Semen(ZSS) is an edible TCM derived from the dried ripe seeds of Ziziphus jujube Mill. var. spinosa(Bunge)Hu ex H. F. Chou(Rhamnaceae), which has the effects of nourishing the heart, tonifying the liver, calming the heart, tranquilizing the mind, arresting sweating, and promoting fluid production, and is widely used in the treatment and health care of diseases related to cardiovascular, nervous, and immune systems. Jujuboside B(JuB), one of the main active ingredients of ZSS, possesses various pharmacological effects with application values. This paper reviewed the chemical structure and pharmacological effects of JuB. JuB has sedative, hypnotic, antitumor, anti-platelet, anti-inflammatory, and other biological activities, which shows the potential thera-peutic effects on insomnia, tumors, coronary artery disease, airway inflammation, and liver injury. However, there are some limitations to the results of current studies. More comprehensive studies, including basic research and clinical trials, need to be carried out to provide more reliable evidence.

Platelet Parameters, C-Reactive Protein, and Depression: An Association Study.

OBJECTIVE: This study aims to investigate the correlation of platelet parameters and C-reactive protein (CRP) with depression. METHODS: The clinical data of 61 patients with depression and 30 healthy control subjects were collected to compare the platelet parameters, CRP levels, and Hamilton Depression Rating Scale (HAMD) scores of the two groups for correlation analysis. RESULTS: The results revealed that the body mass index (BMI) of patients with depression was lower (P < 0.05) than that of the healthy control subjects, and that this difference was more significant in women than in men. Patients with severe depression showed an increased mean platelet volume (MPV) (P < 0.05). In the patients with depression, MPV was positively correlated (P < 0.05) with HAMD scores for work and interest, gastrointestinal symptoms, hopelessness, the anxiety/somatization factor, and the hopelessness factor. Platelet count (PLT) was negatively correlated (P < 0.05) with HAMD scores for hypochondriasis, and plateletcrit (PCT) was negatively correlated (P < 0.05) with HAMD scores for middle insomnia and hypochondriasis. Platelet distribution width (PDW) was positively correlated (P < 0.05) with HAMD scores for gastrointestinal and systemic symptoms as well as hopelessness. Higher CRP levels (P < 0.05) were found in the patients with depression than in the healthy control subjects. Furthermore, in the patients with depression, CRP levels were positively correlated (P < 0.05) with HAMD scores for guilt and the cognitive impairment factor. CONCLUSION: Classical platelet parameters (PLT, MPV, PCT, PDW) and CRP were shown to be associated with specific depressive symptoms and cognitive impairment factors, including sleep, gastrointestinal symptoms, hypochondriasis, losing interest in work, and despair. These results suggest that both platelet parameters and CRP could be suitable biomarkers for predicting the occurrence and prognosis of depression, thus providing a new target for its treatment.

Construction and Evaluation of Metastatic Risk Model in Left and Right Colorectal Cancer / 肿瘤防治研究

Objective To identify the influence factors and construct a predicted model for liver, lung, bone, or brain metastasis among patients with left or right colorectal cancer. Methods Patients with colorectal cancer with information on liver, lung, bone, and brain metastasis were retrospectively filtered and analyzed from 2010 to 2018 from the SEER database. These patients were divided into three groups based on their primary tumor location. Multivariate logistic regression analysis was conducted to identify the influence factors on metastasis. A nomogram that could predict metastasis was established and further validated by the AUC of ROC curves. Results A total of 49335 eligible patients were chosen from the SEER database. N stage and CEA were identified as risk factors for all metastases, which were unrelated to primary tumor location. By contrast, race had varying effects on liver metastasis between different groups (P < 0.05). The nomogram model predicting liver metastasis was successfully established, and the AUCs based on the three groups were 0.821 (95%CI: 0.813-0.830), 0.841 (95%CI: 0.833-0.848), and 0.796 (95%CI: 0.782-0.811), respectively. Conclusion The influence factors and predictive models on liver metastasis were different in patients with colorectal cancer and different primary tumor locations.

Retrospective analysis on 77 cases of T4b hypopharyngeal carcinoma treated by non-surgical treatments / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the effectiveness, safety and factors influencing the clinical prognosis of patients with hypopharyngeal carcinoma in T4b by nonsurgical treatments. Methods: The clinical data of 77 patients with T4b hypopharyngeal cancer treated in the College of Otolaryngology Head and Neck Surgery of the Chinese People's Liberation Army General Hospital from January 2010 to June 2021 were analyzed retrospectively. All were males, aged(57.0±8.0)years old. Patients were treated with induction chemotherapy plus concurrent chemoradiotherapy. Kaplan Meier survival analysis was used to compare the effects of different factors on prognosis. Adverse reactions during treatments and the causes of death were analyzed. Results: 98.7% of 77 patients with T4b hypopharyngeal cancer completed the chemotherapy plan and 94.8% completed the radiotherapy plan. The most common adverse reactions were grade 2 radiation oral mucositis (50/77, 64.9%) and grade 2 leukopenia (50/77, 64.9%). The incidence of grade 3 severe hoarseness was 7.8% (6/77), one patient (1.3%) underwent gastrostomy due to dysphagia, and pronunciation and swallowing function were effectively preserved in other patients. The overall survival rate was 71.9% at 1 year, 45.6% at 3 years and 29.7% at 5 years. The location of tumor, the presence of liquefaction necrosis in tumor, the use of molecular targeted drugs and the approach of radiotherapy were independent factors,each of which that affected the prognosis of T4b patients with advanced hypopharyngeal cancer [HR (95%CI) were 1.867(1.085-3.213), 3.018 (1.437-6.335), 0.372 (0.181-0.764) and 2.158 (1.015-4.588), respectively, P<0.05]. The two leading causes of death with high incidence were disease recurrence (12/32, 37.5%) and cervical large vessel rupture and hemorrhage (11/32, 34.4%). Conclusions: Non-surgical comprehensive treatment offers a high laryngeal preservation rate in patients with T4b hypopharyngeal cancer. The location of tumor, the liquefaction necrosis within tumor, the use of molecular targeted drugs, and the approach of radiotherapy are independent prognostic factors.

Effect of high-intensity interval exercise on depression-related behavior in mice / 生理学报

This paper was aimed to clarify the effect of high-intensity interval training (HIIT) on depression. Animal running platforms were used to establish HIIT exercise models, depression models were prepared by chronic unpredictable mild stress (CUMS), and depression-related behaviors were detected by behavioral experiments. The results showed that HIIT exercise improved depression-related behavior in CUMS model mice. Western blot and ELISA results showed that in the hippocampus, medial prefrontal cortex (mPFC) and amygdala of the CUMS model mice, glucocorticoid receptor (GR) protein expression was down-regulated, and the content of tumor necrosis factor α (TNF-α) was increased, compared with those in the control group, whereas HIIT exercise could effectively reverse these changes in CUMS model mice. These results suggest that HIIT exercise can exert antidepressant effect, which brings new ideas and means for the clinical treatment of depressive diseases.

Simultaneous determination of five constituents in Beisheng granules by UPLC-full wavelength scanning method / 国际中医中药杂志

Objective:To establish the method for simultaneous determination of ginsenoside Rb1, calycosin7-O-β-D-glucopyranoside, 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside (stilbene glucoside), ferulic acid, and rhein in Beisheng granules by UPLC-full wavelength scanning method. Methods:The Waters-ACQUITY UPLC HSS T3 (2.1 mm×100 mm, 1.8 μm) chromatographic column was used. The mobile phase was acetonitrile and 0.1% formic acid-water solute, a linear gradient, the flow rate was 0.3 ml/min and full-wavelength scanning with detection wavelength of 190-400 nm. The column temperature was 30 ℃, and sample volumn was 3 μl.Results:Ginsenoside Rb1, calycosin7-O-β-D-glucopyranoside, stilbene glucoside, ferulic acid and rhein were well separated at 203, 260, 320, 316 and 254 nm wavelength, respectively. The linear ranges were 0.013-0.210 μg ( r=0.999 4), 0.027-0.432 μg ( r=0.999 9), 0.038-0.600 μg ( r=0.999 9), 0.005-0.084 μg ( r=0.999 9), 0.003-0.048 μg ( r=0.999 2). The RSDs of precision, repeatability and stability tests were 0.17%-1.73%, 0.40%-1.49%, 0.21%-1.98% ( n=6), respectively. The recovery rates were 92.71%, 92.44%, 96.83%, 105.71% and 102.61% ( n=6), respectively. Conclusions:The method is simple, rapid and accurate, and can be used as a reference for quality control of Beisheng granules.

Efficacy of weight management combined with uvulopalatopharyngoplasty for obesityrelated obstructive sleep apnea-hypopnea syndrome / 南方医科大学学报

OBJECTIVE@#To evaluate the clinical efficacy of weight management combined with pharyngoplasty for treatment of obesity-related obstructive sleep apnea-hypopnea syndrome (OSAHS).@*METHODS@#Sixty obese patients with OSAHS were randomly assigned into the combined treatment group and control group (@*RESULTS@#After 6 months of treatment, the patients receiving the combined treatment showed significant reductions of BMI, neck circumference and waist circumference as compared with the measurements before treatment and with those in the control group (@*CONCLUSIONS@#Weight management combined with uvulopalatopharyngoplasty can produce a good clinical efficacy for treatment of OSAHS with obesity, and the patients should have strengthened continuous family weight management while receiving surgical treatment.

Application of warm liquid in proximal femoral nail antirotation(PFNA) internal fixation / 中国骨伤

OBJECTIVE@#To investigate the effect and application of warm fluid in patients with proximal femoral nail antirotation(PFNA) internal fixation.@*METHODS@#From November 2012 to December 2016, 80 patients with femoral intertrochanteric fracture were treated with PFNA internal fixation, including 35 males and 45 females, aged from 62 to 90 years old. The patients were divided into two groups. In the control group 40 patients were infused and rinsed at the normal temperature liquid(22 to 24 °C) during the operation; in the experimental group 40 patients were infused and rinsed at warm liquid(36.5 to 37.5 °C). The amount of bleeding, the temperature, the occurrence of shiver and the C-reaction protein in the two groups were analyzed.@*RESULTS@#The incidence of hypothermia and shiver in the experimental group was significantly lower than that in the control group(<0.05). The amount of intraoperative bleeding and C-reaction protein were significantly decreased(<0.05).@*CONCLUSIONS@#The application of warm liquid infusion and flushing in PFNA internal fixation can effectively reduce the incidence of hypothermia and shiver, reduce the amount of bleeding in the operation and the infection rate of the surgical site, improve the comfort of the patients, and ensure the safety of the patients.

Investigation of prevalence and risk factors of H-type hypertension among middle-aged and elderly people in Beijing community / 中国医师进修杂志

Objective To investigate the prevalence and risk factors of H-type hypertension among middle-aged and elderly people in Beijing community. Methods A cross-sectional study by recruiting 1 458 middle-aged and elderly people from a cohort of the "Beijing Longitudinal Study of Aging" in 2009 was conducted. All participants were asked to complete a standardized questionnaire, physical examination and laboratory examinations. Hyperhomocysteinemia was defined as homocysteine (Hcy) > 15 μmol/L, and H- type hypertension was defined as having hypertension and hyperhomocysteinemia simultaneously. The prevalence of H-type hypertension was estimated by using the results of 2000 Beijing population census to weight the data. Multivariate Logistic regression analysis was preformed to estimate the associated factors of H-type hypertension. Results The age was (69.48 ± 8.09) years, and the distribution of Hcy was skewed with the median of 16.56 μmol/L. After weight, the prevalence of hyperhomocysteinemia was 57.20% (834/1 458), and the prevalence of H-type hypertension was 35.32% (515/1 458), accounting for 59.47% (515/866) in patients with hypertension. The ageing, male, hyperuricemia, estimated glomerular filtration rate (eGFR) and insufficiency of fishes/ shrimps were independent risk factors of H-type hypertension ( OR = 2.30, 1.04, 1.02, 0.95 and 0.67; 95% CI 1.54-3.44, 1.02-1.06, 1.04-1.06, 0.94-0.97 and 0.46-0.97; P＜0.01 or＜0.05). Conclusions The proportion of H-type hypertension is high in the middle-aged and elderly people in Beijing community. Lowering uric acid, protection of renal function and intake sufficient fishes and shrimps might prevent and control H-type hypertension.

Dual Effect of Hepatic Macrophages on Liver Ischemia and Reperfusion Injury during Liver Transplantation

Ischemia-reperfusion injury (IRI) is a major complication in liver transplantation (LT) and it is closely related to the recovery of grafts' function. Researches has verified that both innate and adaptive immune system are involved in the development of IRI and Kupffer cell (KC), the resident macrophages in the liver, play a pivotal role both in triggering and sustaining the sterile inflammation. Damage-associated molecular patterns (DAMPs), released by the initial dead cell because of the ischemia insult, firstly activate the KC through pattern recognition receptors (PRRs) such as toll-like receptors. Activated KCs is the dominant players in the IRI as it can secret various pro-inflammatory cytokines to exacerbate the injury and recruit other types of immune cells from the circulation. On the other hand, KCs can also serve in a contrary way to ameliorate IRI by upregulating the anti-inflammatory factors. Moreover, new standpoint has been put forward that KCs and macrophages from the circulation may function in different way to influence the inflammation. Managements towards KCs are expected to be the effective way to improve the IRI.

Prevalence, awareness, treatment and control of hypertension in population older than 15 years of age in Beijing, 2013-2014 / 中华流行病学杂志

Objective To investigate the rates on prevalence,awareness,treatment and control of hypertension in population older than 15 years of age in Beijing,2013-2014.Methods A cross-sectional survey was conducted in Beijing between 2013-2014.Stratified multistage random sampling method was used to select representative sample of 13 057 Chinese individuals aged over 15 years,from the general population.Blood pressure was measured for three readings at sitting position after resting for at least five minutes with an average reading recorded.A standardized structured questionnaire was developed to collect history of hypertension and antihypertensive treatment.Results A total of 4 663 community residents aged over 15 years were hypertensive among the 13 057 individuals,with the standardized prevalence rate as 32.7％,in Beijing area.The age-standardized prevalence rates of hypertension appeared 34.6％ in men and 30.8％ in women.The age-and sexstandardized prevalence of hypertension rates were 33.3％ in urban and 24.6％ in rural areas.The prevalence of hypertension increased with age and appeared higher in men than in women,in urban than in rural residents.Among the hypertensive patients,rates of awareness,treatment and control were 66.8％,64.6％ and 31.6％,respectively.Conclusion High prevalence of hypertension with low rates on awareness and treatment and control,appeared in the general population of Beijing.Related strategies should be developed regarding prevention,control and management of hypertension,to reduce the burden of this disease.

Prevalence, awareness, treatment and control of hypertension in population older than 15 years of age in Beijing, 2013-2014 / 中华流行病学杂志

Objective To investigate the rates on prevalence,awareness,treatment and control of hypertension in population older than 15 years of age in Beijing,2013-2014.Methods A cross-sectional survey was conducted in Beijing between 2013-2014.Stratified multistage random sampling method was used to select representative sample of 13 057 Chinese individuals aged over 15 years,from the general population.Blood pressure was measured for three readings at sitting position after resting for at least five minutes with an average reading recorded.A standardized structured questionnaire was developed to collect history of hypertension and antihypertensive treatment.Results A total of 4 663 community residents aged over 15 years were hypertensive among the 13 057 individuals,with the standardized prevalence rate as 32.7％,in Beijing area.The age-standardized prevalence rates of hypertension appeared 34.6％ in men and 30.8％ in women.The age-and sexstandardized prevalence of hypertension rates were 33.3％ in urban and 24.6％ in rural areas.The prevalence of hypertension increased with age and appeared higher in men than in women,in urban than in rural residents.Among the hypertensive patients,rates of awareness,treatment and control were 66.8％,64.6％ and 31.6％,respectively.Conclusion High prevalence of hypertension with low rates on awareness and treatment and control,appeared in the general population of Beijing.Related strategies should be developed regarding prevention,control and management of hypertension,to reduce the burden of this disease.

Clinical efficacy and safety of re-radiotherapy combined with tegafur gimeracil oteracil potassium capsule in treatment of local recurrent esophageal carcinoma / 国际肿瘤学杂志

Objective To investigate the clinical efficacy and safety of re-radiotherapy combined with TS-1 (tegafur gimeracil oteracil potassium capsule) in treatment of local recurrent esophageal carcinoma.Methods A total of 63 esophageal carcinoma patients who recurred after the first course radiation treatment admitted to Jiangdu People's Hospital of Yangzhou during January 1,2012 to June 30,2015 were retrospectively analyzed.Twenty-seven of them treated with re-radiotherapy combined with TS-1 were deemed as the research group and 36 of them treated with radiotherapy alone were deemed as the control group based on different treatment.Then the clinical efficacy and adverse reactions of the two groups were compared.Results The objective response rates were 77.8％ (21/27) and 50.0％ (18/36) respectively in the research group and control group,and the difference was statistically significant (x2 =5.048,P =0.025).The median survival time in the two groups were 21.6 months and 13.7 months,the 1-year (74.1％) and 2-year (44.4％) survival rates of the research group were both higher than those of the control group (52.8％ and 30.6％,respectively),and the difference was statistically significant (x2 =6.086,P =0.013).The major adverse effects of the research group and control group during the treatment were radiation oesophagitis (92.6％ vs.80.5％),radiation pneumonia (18.5％ vs.19.4％),myelosuppression (96.3％ vs.77.8％) and gastrointestinal reactions (25.9％ vs.19.4％).Most of them were 1-2 grade,and there were no statistically significant differences (x2 =0.975,P =0.323;x2 =0.009,P =0.926;x2 =2.941,P =0.086;x2 =0.375,P =0.540).Conclusion The treatment of re-radiotherapy combined with TS-1 for local recurrent esophageal carcinoma can improve the efficacy and prolong survival period,and the adverse reactions are tolerable.

Protective effect of GLP-1 against AGEs-induced H9 C2 myocardial cell apoptosis / 中国药理学通报

Aim To investigate the protective effect of Glucogon like pep tide-1 (GLP-1 )on H9C2 cardio-myocytes against AGEs-induced apoptosis and the po-tential molecular mechanisms.Methods H9 C2 car-diomyocytes cells cultured in vitro were divided into the following groups:normal control group ,1 0 0 mg · L-1 AGEs group,100 mg·L-1 AGEs+10 nmol·L-1 GLP-1 group,100 mg·L-1 AGEs+5 mmol·L-1 N-acetyl-cysteine (NAC)group.Cell viabillity rate was meas-ured by CCK-8 assay,ROS production was measured by DCFH-DA fluorescent probe;Cells in different groups were stained with Annexin V-FITC/PI and then apoptotic rate was detected by flow cytometry;Nucleus morphology was observed under fluorescence micro-scope after being incubated with Honchest 33258;Bax, Bcl-2 mRNA gene expression was measured using RT-PCR;Western blot was applied to assess the apoptotic components expression including Bax and Bcl-2.Re-sult Compared with control group,cell viability rate in AGEs group was decreased in a dose-dependent manner;cell apoptosis and ROS production in H9 C2 cells were remarkably increased in AGEs group.How-ever,compared with AGEs group,GLP-1 reduced ROS production and ameliorated cell apoptosis caused by AGEs;the expression of pro-apototic proteins Bax was decreased,the expression of anti-apoptotic proteins like Bcl-2 was increased. Conclusion GLP-1 protects H9 C2 cardiomyocytes against AGEs-induced apoptosis, which may be related to the reduction of the active oxy-gen (ROS).

Epidemiological Features of Nontraumatic Spontaneous Subarachnoid Hemorrhage in China: A Nationwide Hospital-based Multicenter Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Nontraumatic spontaneous subarachnoid hemorrhage (SAH) is associated with a high mortality. This study was conducted to investigate the epidemiological features of nontraumatic spontaneous SAH in China.</p><p><b>METHODS</b>From January 2006 to December 2008, the clinical data of patients with nontraumatic SAH from 32 major neurosurgical centers of China were evaluated. Emergent digital subtraction angiography (DSA) was performed for the diagnosis of SAH sources in the acute stage of SAH (≤3 days). The results and complications of emergent DSA were analyzed. Repeated DSA or computed tomography angiography (CTA) was suggested 2 weeks later if initial angiographic result was negative.</p><p><b>RESULTS</b>A total of 2562 patients were enrolled, including 81.4% of aneurysmal SAH and 18.6% of nonaneurysmal SAH. The total complication rate of emergent DSA was 3.9% without any mortality. Among the patients with aneurysmal SAH, 321 cases (15.4%) had multiple aneurysms, and a total of 2435 aneurysms were detected. The aneurysms mostly originated from the anterior communicating artery (30.1%), posterior communicating artery (28.7%), and middle cerebral artery (15.9%). Among the nonaneurysmal SAH cases, 76.5% (n = 365) had negative initial DSA, including 62 cases with peri-mesencephalic nonaneurysmal SAH (PNSAH). Repeated DSA or CTA was performed in 252 patients with negative initial DSA, including 45 PNSAH cases. Among them, the repeated angiographic results remained negative in 45 PNSAH cases, but 28 (13.5%) intracranial aneurysms were detected in the remaining 207 cases. In addition, brain arteriovenous malformation (AVM, 7.5%), Moyamoya disease (7.3%), stenosis or sclerosis of the cerebral artery (2.7%), and dural arteriovenous fistula or carotid cavernous fistula (2.3%) were the major causes of nonaneurysmal SAH.</p><p><b>CONCLUSIONS</b>DSA can be performed safely for pathological diagnosis in the acute stage of SAH. Ruptured intracranial aneurysms, AVM, and Moyamoya disease are the major causes of SAH detected by emergent DSA in China.</p>

Three-Dimensional-Printing of Bio-Inspired Composites.

Optimized for millions of years, natural materials often outperform synthetic materials due to their hierarchical structures and multifunctional abilities. They usually feature a complex architecture that consists of simple building blocks. Indeed, many natural materials such as bone, nacre, hair, and spider silk, have outstanding material properties, making them applicable to engineering applications that may require both mechanical resilience and environmental compatibility. However, such natural materials are very difficult to harvest in bulk, and may be toxic in the way they occur naturally, and therefore, it is critical to use alternative methods to fabricate materials that have material functions similar to material function as their natural counterparts for large-scale applications. Recent progress in additive manufacturing, especially the ability to print multiple materials at upper micrometer resolution, has given researchers an excellent instrument to design and reconstruct natural-inspired materials. The most advanced 3D-printer can now be used to manufacture samples to emulate their geometry and material composition with high fidelity. Its capabilities, in combination with computational modeling, have provided us even more opportunities for designing, optimizing, and testing the function of composite materials, in order to achieve composites of high mechanical resilience and reliability. In this review article, we focus on the advanced material properties of several multifunctional biological materials and discuss how the advanced 3D-printing techniques can be used to mimic their architectures and functions. Lastly, we discuss the limitations of 3D-printing, suggest possible future developments, and discuss applications using bio-inspired materials as a tool in bioengineering and other fields.

A Mitochondrial DNA A8701G Mutation Associated with Maternally Inherited Hypertension and Dilated Cardiomyopathy in a Chinese Pedigree of a Consanguineous Marriage / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cardiovascular diseases, including dilated cardiomyopathy (DCM) and hypertension, are the leading cause of death worldwide. The role of mitochondrial DNA (mtDNA) in the pathogenesis of these diseases has not been completely clarified. In this study, we evaluate whether A8701G mutation is associated with maternally inherited hypertension and DCM in a Chinese pedigree of a consanguineous marriage.</p><p><b>METHODS</b>Fourteen subjects in a three-generation Han Chinese family with hypertension and DCM, in which consanguineous marriage was present in the parental generation, were interviewed. We divided all the family members into case (7 maternal members) and control group (7 nonmaternal members) for comparison. Clinical evaluations and sequence analysis of mtDNA were obtained from all participants. Frequency differences between maternal and nonmaternal members were tested to locate the disease-associated mutations.</p><p><b>RESULTS</b>The majority of the family members presented with a maternal inheritance of hypertension and DCM. Sequence analysis of mtDNA in this pedigree identified eight mtDNA mutations. Among the mutations identified, there was only one significant mutation: A8701G (P = 0.005), which is a homoplasmic mitochondrial missense mutation in all the matrilineal relatives. There was no clear evidence for any synergistic effects between A8701G and other mutations.</p><p><b>CONCLUSIONS</b>A8701G mutation may act as an inherited risk factor for the matrilineal transmission of hypertension and DCM in conjunction with genetic disorders caused by consanguineous marriage.</p>