The exploration of drug toxicity and mechanisms is a vital component in ensuring the safe use of drugs in clinical practice, as this topic has attracted widespread concern. The intestinal flora holds great significance for drug metabolism, efficacy and mechanism, and is an instrumental metabolic organ that facilitates material information transfer and biotransformation. However, an increasing number of studies have shown that intestinal bacteria are closely related to the toxicity of specific drugs. On the one hand, drugs are transformed into toxic metabolites under the influence of intestinal bacteria, thus inducing direct drug toxicity. On the other hand, the composition and function of the intestinal flora are altered under drug influence, resulting in disruption of endogenous metabolic pathways. Consequently, this disruption compromises the intestinal barrier and affects other organs, leading to indirect drug toxicity. This review meticulously compiles recent examples of drug toxicity attributed to intestinal bacteria, explores in depth the contention that metabolic enzymes of gut microbiota may be of great influence on oral drug toxicity, and outlines prospective avenues for future research on gut microbiota and drug toxicity and mechanisms. This not only provides novel perspectives for the judicious clinical utilization of drugs but also offers insights for the safety assessment of innovative pharmaceuticals.

Objective To assess the current status of knowledge, attitude and practice (KAP) towards antibiotic use among community residents in Hangzhou, and to explore the correlations among them. Methods A total of 449 permanent residents in Hangzhou were randomly selected using a multistage stratified random sampling method. Self-reported data on basic demographic factors, and relevant KAP information were collected by the questionnaire survey. Differences in KAP scores according to each demographic factor were assessed by the t test or ANOVA test, and AMOS 21.0 was used for the path analysis. Results Scores for knowledge, attitude and practice regarding antibiotic use were (6.17±2.45), (6.45±0.99) and (6.21±1.02) respectively. Results of the path analysis showed that education level and age had effects on the knowledge (coefficients: 0.57 and -0.38 respectively) . Age, gender and knowledge had effects on the attitude (coefficients: -0.27, 0.12 和 0.02 respectively), and attitudes, gender, monthly income and the level of education had effects on the practice (coefficients: 0.48、 0.37、 0.06 and 0.02 respectively) . Conclusion Community residents in Hangzhou lack relevant knowledge, and there are some irrational attitudes and practices regarding antibiotic use. There is a correlation between knowledge and attitudes, as well as between attitudes and practices, but the knowledge and practices are not correlated.

OJECTIVETo observe the effect of tianma gouteng decoction (TGD) on the endothelial function and the renal protein expression of spontaneously hypertensive rats, and to analyze its possible mechanism.

METHODSTotally 18 6-week-old SHR were randomly divided into 3 groups according to randomized block design, the SHR control group, the TGD group, and the captopril group, 6 in each group. Meanwhile, Wistar Kyoto (WKY) rats of the same age were recruited as a WKY control group. Rats in the TGD group were administered with TGD at the daily dose of 10. 260 g/kg. Rats in the captopril group were administered with captopril at the daily dose of 3. 375 g/kg. 2 mL/100 g distilled water was administered to rats in the SHR control group and the WKY control group. All medication was performed by gastrogavage once per day till rats were 24 weeks old. Changes of blood pressure were measured once per two weeks. The relaxation of the thoracic aorta and the superior mesenteric artery was determined by vascular ring in vitro to reflect the endothelial function. The total renal protein was separated by two-dimensional electrophoresis (2-DE). The significantly deviated protein was verified by Western blot.

RESULTS(1) Compared with the SHR control group, blood pressure was significantly lowered in rats (10 - 24 weeks old) of the captopril group (P <0.01, P <0.05). The hypotensive effect of TGD was obvious at the beginning of hypertension (10 -12 weeks) (P <0. 01). But along with the progression of hypertension, its hypotensive effect was not obvious (P>0. 05). (2) Compared with the SHR control group, the relaxation of the superior mesenteric artery was obviously improved in the TGD group (P <0. 05); the relaxation of the thoracic aorta and the superior mesenteric artery was obviously superior in the WKY control group (P <0. 01, P <0. 05). But there was no statistical difference in each relaxation index between the captopril group and the SHR control group (P >0. 05).(3) RESULTS: of 2-DE found 16 significantly differential renal protein, mainly involved nitric oxide (NO) system, oxidative stress, and cytoskeleton-related proteins. Results of Western blot showed that TGD could significantly improve expressions of Cu-Zn superoxide dismutase (SOD), N(G, N(G)-dimethylarginine dimethylaminohydrolase 2 (DDAH2), and pterin-4-alpha-carbinolamine dehydratase 1 (PCBD1) (P <0. 05).

CONCLUSIONGTD could protect the endothelial function of the superior mesenteric artery in SHR, and its intervention mechanism of hypertension induced early renal injury might be relevant to regulating the NO system and antioxidative stress.

Animals ; Blood Pressure ; Captopril ; Drugs, Chinese Herbal ; therapeutic use ; Hypertension ; drug therapy ; Kidney ; metabolism ; Oxidative Stress ; Proteins ; metabolism ; Proteomics ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Superoxide Dismutase ; metabolism

Background and purpose:Cancer is a common disease. Multidisciplinary approach is the best model for cancer treatment. Cancer staging is the basis for diagnosis, treatments and prediction of prognosis.The survey is to give an overview of the current application of cancer multidisciplinary approach and UICC or other international cancer staging in mainland China. We made inquiries to our Chinese oncologists’ experience of using these staging and share their comments and recommendations. For those cancers common in China, Chinese oncologists and academic societies should provide more information of staging, therapies, outcome, prognostic predictors of prognosis, etc. to make international stage systems, like UICC or AJCC, a more appropriate, accurate and acceptable guide to individual patients’ staging and treatment, to predict outcome and to facilitate clinical trials better. Methods: This survey was done from 2012 to 2013 by questionnaires. The questions were answered for 10 major cancers in China (liver cancer, esophageal cancer, nasopharyngeal carcinoma, lung carcinoma, breast cancer, gastric cancer, colorectal cancer, gynecologic cancer, prostate cancer and lymphoma). Thirty-three questionnaires have been answered by national wide hospitals including provincial cancer hospitals, district cancer hospitals and departments of oncology in general hospitals. We also site visited 7 grade B hospitals. Results:Multidisciplinary approach is not widely used in the hospitals. UICC or AJCC stages have been widely used for 10 cancers, but for cancers that were uncommon in the West;while common in China (nasopharyngeal carcinoma, liver cancer) the staging proposed by Chinese society have also been used to replace UICC/AJCC. Conclusion:We suggest a wild implementation of multidisciplinary approach. For those cancers common in China Chinese oncologists and academic societies should provide more information of staging, therapies, outcome, prognostic predictors of prognosis etc. to make international stage systems, like UICC or AJCC, a more appropriate, accurate and acceptable guide to individual patients’ staging and treatments, to predict outcome and to facilitate clinical trials better.

CMTM family is silenced and down-regulated in several kinds of tumors.Its aberrant expression has a strong association with the development,progression and metastasis of tumors.Thus,CMTM family is potential tumor suppressor genes.Epigenetics mechanism is the essential mechanism of the aberrant expression in this gene family.The discovery of this research gives a new direction to the clinical treatment of tumor.

Objective To discuss the effect of mirtazapine in depressive functional dyspepsia patients with weight loss (FD-WL).Methods As a randomized and controlled trial,seventy-two FD patients with weight loss and depression were randomly divided into mirtazapine group(n=24),paroxetine group(n=23) and conventional group(n=25),and all patients were treated for 8 weeks.The Nepean Dyspepsia Index (NDI)-symptom checklist,the Hamilton Rating Scale of Depression (HAMD),body weight were assessed before the treatment and after 2,4,6,8 week.Results (1) After 2-week treatment,the scores of NDI-symptom checklist and HAMD in mirtazapine group were significantly lower than that in paroxetine group and conventional group.After 4-week,6-week and 8-week treatment,the score of HAMD in mirtazapine group((13.34±1.52),(11.65±1.56),(10.15±1.36)) and paroxetine group((13.65±1.81),(11.34±1.21),(9.58±1.41))was significantly lower than that in conventional group((18.15±1.61),(17.20±2.14),(15.30±1.56)) (all P<0.05).But there was no statistically difference between mirtazapine group and paroxetine group (P>0.05).(2) After 6-week and 8-week treatment,the body weight in mirtazapine group((53.17±6.46)kg,(53.55±6.52)kg)was significantly higher compared with that in paroxetine group((49.47±5.72)kg,(49.57±5.81)kg)and conventional group((48.69±5.60)kg,(48.68±5.65)kg)(all P<0.05).After 8-week treatment,patients in mirtazapine group experienced a weight gain of(3.34±1.82)kg.Conclusion Mirtazapine not only can significantly improve dyspepsia symptoms and depressive scoring,but also can increase body weight.

ObjectiveTo investigate the clinical characteristics of the inpatients suffering from dengue fever in order to provide references for better diagnosis and treatment.Methods The clinical data of 158 dengue fever patients admitted to the First Affiliated Hospital of Sun Yat-Sen University from July 23rd to October 31st, 2014 during the 2014 epidemic in Guangzhou area were retrospectively analyzed, including general clinical manifestations, conventional examinations, pathogenesis, and prognosis.Results The mean age of the 158 patients was (56±20) years, with half of them over 60 years old (79 cases). Among them, 94 (59.49%) were male.① The common manifestations included fever (100%), headache (70.89%), myalgia/bone soreness (62.03%), and skin rash (54.43%). Bleeding and plasma leakage were found in 25.95% and 14.56% of the patients respectively.② Laboratory examination:leucopenia (75.32%) and thrombocytopenia (77.85%) were found, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated in 57.59% and 77.85% of the patients respectively. However, elevation of blood hematocrit was rare (1.27%).③ It was found that in the acute phase (0 - 5 days of the onset), serum dengue virus antibody IgM (DF-IgM) was positive in 63.54% of the patients (61/96), and 92.62% (113/122) of patients were dengue virus RNA (DENA-RNA) positive.④ The rate of comorbidity in this study was 55.06% (87/158), including hypertension (27.22%) and type 2 diabetes (15.82%), which were the two most common co-morbidities.⑤ All the patients were given supportive therapy to prevent complications. They were also isolated for more than 5 days after onset, and at least for 24 hours after subsidence of fever in addition.⑥ The criteria for the diagnosis of severe dengue were fulfilled in 18 patients (11.39%). One patient died of massive hemorrhage from gastro-intestinal tract, and 1 patient voluntarily left hospital with untreated multiple organ dysfunction syndrome (MODS). Another 2 patients of dengue fever died from primary cardio-cerebrovascular disease, and the remaining 154 patients (97.47%) fully recovered with supportive therapy and complication prevention measures.Conclusions The clinical manifestations of inpatients with dengue fever in this study were typical, and they manifested a higher incidence of severe illness. DENA-RNA could be a sensitive indicator for early pathogenic diagnosis. With symptomatic and supportive therapy, most patients had a good outcome. However, early diagnosis and clinical interventions of severe dengue still need further studies.

Objective To observe the functional connectivity (FC) pattern linking the hippocampus with the rest of the brain in ischemic stroke patients with cognitive dysfunction,especially the default mode network (DMN).Methods Resting-state functional connectivity magnetic resonance imaging (fMRI) was performed on 15 ischemic stroke patients with cognitive dysfunction (the patient group) and 10 normal elderly controls.The bilateral hippocampus was the region of interest.Correlation analyses yielded a mapping of cerebral functional connectivity activation for both groups.Results Compared with the healthy controls,the patient group showed weakened functional connectivity between the hippocampus and other regions including the cingulate gyrus,the superior,middle and inferior frontal lobes,the inferior parietal lobule and the superior temporal gyrus.But there was enhanced functional connectivity with the cerebellar posterior lobe,the occipital lobe,the medial temporal lobe,the precuneus and the calcarine.The results were significantly different between the two groups.Conclusion The functional connectivity pattern of the hippocampus is impaired in stroke patients with cognitive dysfunction.Reduced functional connectivity between brain regions may be one cause of cognitive dysfunction after stroke,and enhanced functional connectivity may be an appropriate compensatory mechanism.

Objective: To use autophagy inhibitors combined with radiation to treat the oral squamous cell carcinoma CAL-27 and KB cells,and to explore the influence of autophagy in the oral cancer radiation sensitivity and its mechanisms. Methods:The human oral squamous cell carcinoma CAL-27 and KB cells were divided into control group,CQ group,3-MA group,IR group,CQ+IR group,and 3-MA+IR group. The survival rate was detected by MTT method and the autophagy of CAL-27 cells was observed by immunofluorescence method and laser scanning confocal microscope.The expression levels of LC3 and beclin-1 were detected by Western blotting method. The apoptotic rate was determined by flow cytometry with Annexin Ⅴ/PI doulde staining. Results:Compared with IR group,the survival rates in 3-MA + IR and CQ+ IR groups were signifcantly decreased (P < 0.05 ).The autophagy levels of cells in IR group were significantly higher than those in control group, CQ group, 3-MA group,CQ+IR group,and 3-MA+IR group (P <0.05).The expression levels of LC3 and beclin-1 proteins in IR group were significantly higher than those in control group,CQ+ IR group,and 3-MA+ IR group (P < 0.05). The apoptotic rates in IR,3-MA+ IR,and CQ+ IR groups were markedly higher than those in control group. Compared with IR group,the apoptotic rates in CQ+IR and 3-MA+IR groups were significantly increased (P <0.05).Conclusion:Radiotherapy can induce the increase of autophagy level of oral squamous cell carcinoma cells. Inhibiors of autophagy can increase the radio-sensitivity of oral squamous cell carcinoma cells by inhibiting the proliferation and inducing the apoptosis.

Objective To investigate the effects of total flavonoids in Gingko Biloba on glucose and lipid metabolism and liver function in rats with insulin resistance. Methods Forty SD rats were randomly divided into normal control group,model group,total flavonoids in Gingko Biloba group and rosiglitazone group(positive drug control group)(n=10).Models of insulin resistance were established by high glucose and high fat diet in model group,total flavonoids in Gingko Biloba group and rosiglitazone group.After treatment for 12 weeks,serum glucose,serum lipids,and parameters of insulin resistance,liver function and anti-oxidation capability were detected in each group,and histologic observations of liver tissues were conducted with adipose staining. Results The serum glucose,insulin resistance index(HOMA-IR),insulin action index(IAI),serum total cholesterol(TC),triglyceride(TG),liver malondialdehyde(MDA) and serum transaminase activity in total flavonoids in Gingko Biloba group were significantly lower than those in model group(P