Objective To investigate the drug induced liver injure(DILI)associated with Chinese herbal medicine and herbal related food supplements.Methods From 1982 to 2005.8.9 consecutive pa- tients were diagnosed as DILI based on their medication history,clinical manifestation,liver function and other laboratory tests.The final retrospection confirmatory diagnosis was made according to the interna- tional scoring system for DILI.Results The 82 DILI patients(28 men,54 females,age ranging from 16 to 81 years old)accounted for 2.2% of hospitalized patients with liver dysfunction.Among those patients with DILI,30.5% was caused by weight reducing drugs or food supplements,12.2% by drugs of derma tology,8.5% by drugs for cardiovascular disease,8.5% by drugs of rheumatology,7.3% by drugs of gynecology,6.1% by drugs for liver disease,6.1% by blood-lipids modulators,3.7% by drugs for thy- roid disease,3.7% by drugs for hyperplasia of mammary glands and 13.4 % by the others.The duration of medication was from 6 clays to 6 months and the incubation period was from 6 days to 3 months.DILI could be classified as acute hepatocellular injury(36.59%),acute cholestasis(39.02%)and mixtures (24.39%).About 10% patients were accompanied by allergic manifestations.All patients recovered rap- idly after stopping the relevant medicine.Conclusion Chinese herbal medicine and herbal related food supplements are a common cause of DILI in China.The awareness and monitoring improving DILI during herbs treatment is a critical issue in daily practice.

BACKGROUND:Insulin-like growth factor-1 (IGF-1) is an important mitogen and an indispensable regulator during normal hair cell development. Extracellular signal regulated kinase 1/2 (ERK1/2) is also expressed in mammalian vestibular organs.OBJECTIVE: To investigate the changes of the expression and the distribution of IGF-1, IGF-1 receptor (IGF-1R) and ERK1/2 in guinea pig's vestibular epithelium following gentamycin injury.DESIGN: A randomly controlled study.SETTING: Department of Otorhinolaryngology, General Hospital of Chengdu Military Area Command of Chinese PLA.MATERIALS: Twenty healthy and adult guinea pigs, weighing 300 to 350 g, provided by the Experimental Animal Center,Fourth Military Medical University of Chinese PLA, were randomly divided into four experimental groups and a control group with 4 in each group.METHODS: The experiment was performed at Department of Otorhinolaryngology Research Laboratory of Xijing Hospital,Fourth Military Medical University of Chinese PLA from January 2002 to May 2002. In the experimental groups,gentamycin was intraperitoneally administered daily (80 mg/kg) for 10 consecutive days. For the control group, 1 mL of 0.9% sterile saline was administered in the same way. The guinea pigs, in which unsteady gait or nystagmus appeared,could be involved in the further experiments. Before being sacrificed, the animals' gait, nystagmus and the amount of food-intake were observed every day. The animals were anesthetized deeply with 50 mg/kg pentobarbital 1, 7, 14 or 21days after the last gentamycin administration and then decapitated. Bilateral otic vesicles were harvested and immersed in 4% paraformaldehyde. Then the specimens were decalcified in 10% ethylenediamine tetraacetic acid (EDTA),thereafter embedded in OCT gel and serially sectioned at a thickness of 10 μm in the cryostat. The behavioral changes of guinea pigs were observed. The morphological changes of vestibular epithelium were examined by hematoxylin and eosin (HE) staining. The expression and distribution changes of IGF-1/1R and ERK1/2 were investigated immunohistochemically. MAIN OUTCOME MEASURES: The behavioral, morphological, expression and distribution changes of IGF-1/1R and ERK1/2 of guinea pigs in each group.RESULTS: Twenty involved guinea pigs entered the stage of final analysis. ① All the guinea pigs' vestibular functions were impaired after gentamycin treatment, then partially restored without any pharmaceutical treatment. ②Morphological injury was obvious after gentamycin treatment, and improved 1 week later. ③The expression of IGF-1/1R was low in the control group, and in the 1-day group it increased significantly to its maximum. After that, its expression decreased gradually, but was still higher in the 21-day group than that in the control group. There were significant differences in the expression of IGF-1/1R among different groups (F =51.8,45.7,P ＜ 0.05). The expression changes of IGF-1 and its receptor were similar. ④The expression of ERK1/2 was low in the control group, and increased gradually after gentamycin toxicity. In the 7-day group, the immunoreactivity reached its maximum. Then the levels of ERK1/2 decreased gradually, but were still higher in the 21-day group than that in the control group. There were significant differences in the expression of ERK1/2 among different groups (F =103.7,106.4, P ＜ 0.01), but no significant differences existed in the expression between ERK1 and ERK2 among different groups (P ＞ 0.05).CONCLUSION: The expression of IGF-1/1R and ERK1/2 in vestibular epithelium increased after gentamycin treatment,and IGF-1 may play an important role as an endogenous mitogen through a paracrine or autocrine manner in the early stage of hair cell self-repair of guinea pigs. ERK1/2 may play an important role in signal transduction during vestibular hair cell self-repair after gentamycin toxicity in guinea pigs.

AIM: To evaluate the efficiency and complications of single lacrimal duct intubation versus annular lacrimal duct intubation with 5-fluorouracil and tobramycin/dexamethasone eye ointment injection in lacrimal duct obstruction treatment.METHODS:A total of 74 patients (92 eyes) with lacrimal duct obstruction who received surgical treatment by Department of Ophthalmology in Qinhuangdao Haigang Hospital were consecutively recruited between August 2015 and September 2016.They were randomly allocated to Group A or Group B.After probing of lacrimal passage, Group A (46 eyes) were treated by using single lacrimal duct intubation.Group B (46 eyes) were treated by using annular lacrimal duct intubation combined with 5-fluorouracil and tobramycin/dexamethasone eye ointment injection.Between the two groups, Mann-Whitney Rank sum test was used to comparing the operative effect, and Chi-square test was used to comparing the occurrence of complications.RESULTS:The cure rate was 61% in Group A and 89% in Group B;the improvement rate was 22% in Group A and 4% in Group B.Group B had better effect and less complications (2 cases) than Group A (8 cases),the differences between the two groups were significantly(P<0.05).CONCLUSION: Compared with single lacrimal duct intubation, annular lacrimal duct intubation combined with 5-fluorouracil and tobramycin/dexamethasone eye ointment injection has better operative effect and less complication in lacrimal duct obstruction treatment.

AIM: To evaluate the operative effect and time effectiveness of the conventional surgery versus retrograde gas injection under nasal endoscope combined 5-Fluorouracil for lacrimal canalicular rupture.
●METHODS:A total of 67 patients (67 eyes) with lower lacrimal canalicular rupture who received surgical treatment by Department of Ophthalmology in Qinhuangdao Haigang Hospital were consecutively recruited between Jan. 2009 and Dec. 2015. They were randomly divided into Group A or Group B. Group A (33 patients, 33 eyes) were treated by conventional surgery, and Group B ( 34 patients, 34 eyes ) were treated by retrograde gas injection under nasal endoscope combined 5-Fluorouracil. Time for finding out the cute end of the lower lacrimal canaliculus and postoperative effect were recorded. Comparisons between the two groups were done with lndependent sample t-test and Mann-Whitney Rank sum test.
●RESULTS: Time for finding out the cute end of the lower lacrimal canaliculus of Group A was (44. 42±10. 66) min, and the time of Group B was ( 30. 06 ± 6. 21 ) min. There was significant difference between the two groups (t=6. 72, P<0. 05). Lacrimal ducts flush was done at the 6mo after the survey, Group B had better effect than Group A, the difference between the two groups were significant (Z=2. 47,P<0. 05).
●CONCLUSION: Compared with conventional surgery, retrograde gas injection under nasal endoscope combined 5-Fluorouracil for lacrimal canalicular rupture can make the operation time shorter and has better effect.

OBJECTIVETo observe the relation between Pi deficiency syndrome (PDS) and the configuration and functions of extensor digitorum longus (EDL)and soleus (SOL).

METHODSTotally 36 ICR mice were randomly divided into 3 groups according to weight matching principle, the control group, the exhausted group, and the rhubarb group, 12 in each group. Two PDS models were established by either purgation with rhubarb diarrhea (as Group A) or exhausted swimming plus sleep deprivation (as Group B).The cross sectional area (CSA) of type I and II fibers of extensor digitorum longus (EDL) and soleus (SOL), relative proportions of type I and II fibers were measured by m-ATPase histochemical method. The isotonic contraction and the maximum tetanus contraction of EDL and SOL were detected by PowerLab system.

RESULTSCompared with the control group, the body weight, body temperature, and the general health condition of PDS model rats obviously decreased; the spleen index and the thymus index were also lower; the maximal isotonic contraction and the maximum tetanus contraction obviously decreased; the cross section areas of EDL and SOL were reduced with loosely arranged cells. In EDL, the proportion of type I fibers was added and the proportion of type II fibers was lowered. In SOL, there was no change in the proportion of type I and type II fibers.

CONCLUSIONSEDL and SOL were obviously atrophied in the two PDS model mice. The type I fibers of SOL was more significantly atrophied in Group B.

Animals ; Autophagy ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cells, Cultured ; Mesenchymal Stromal Cells ; cytology ; Neurons ; cytology ; Rats ; Rats, Sprague-Dawley

OBJECTIVE This study investigated transcriptional regulation of the main chemical con-stituents of Polygonum multiflorum Thunb. including Stilbene Glucoside (THSG) and anthraquinone constituents (Emodin, Rhein, Aloeemodin, Chrysophanol and Physcion) and six potential liver injury constituents(gallic acid,quercetin,luteolin,kaempferol,resveratrol)on mediated by PXR CYP3A4.Early establishment of pregnane X receptor mediated CYP3A4 drug induced rapid screening technique was used to determine the effects of these constituents. METHODS First,effect of constituents on the cell activity was detected by MTS cell viability assay. IC50was calculated. Second, the expression vector and reporter vector were co-transfected into Hep G2 cells,10 μmol·L-1Rifampicin as a positive control, 10 μmol·L-1Ketoconazole as a negative control. After treated with different concentrations of (the an-thraquinone constituents concentrations were 2.5,5 and 10 μmol·L-1;the concentrations of Gallic Acid, Quercetin,Luteolin,Kaempferol,Apigenin,Resveratrol concentrations were 5,10 and 20 μmol·L-1)for 24 h,the cells were tested for dual luciferase activity.RESULTS The results show that the inhibitory ef-fect of THSG,Chrysophanol,Emodin,Rhein and Aloeemodin on CYP3A4 was inhibited by co-transfec-tion of pcDNA3.1 and pGL4.17-CYP3A4. The expression of pcDNA3.14-PXR and pGL4.17-CYP3A4 was induced by the four constituents. Besides, Emodin has a directly inducing effect. Four anthraqui-none constituentscan induce the effect of CYP3A4 by PXR, but Emodin can directly induce CYP3A4. THSG can inhibit CYP3A4,but in the presence of PXR plasmid can induce CYP3A4.For the six poten-tial liver injury constituents, results show that the plasmid pcDNA3.1 was cotransfected with pGL4.17-CYP3A4 regulation of Gallic Acid and Resveratrol on CYP3A4 inhibitory effects of Quercetin,Luteolin, Kaempferol have an induce effect; after pcDNA3.14-PXR and pGL4.17-CYP3A4 cotransfected, Quercetin, Luteolin, Kaempferol, Apigenin, Resveratrol have induced effect, three constituents'induc-tion effect had significant difference.CONCLUSION 12 kinds of Polygonum multiflorum Thunb.constit-uents have inhibitory or activating effects on CYP3A4, after the participation of PXR, 9 components have induced effects on CYP3A4, and the induction effect of 6 components has significant difference. The results suggested that we should pay attention to potential drug interactions when combined with Polygonum multiflorum Thunb.,and improve safety and efficacy.

Prostate cancer is one of the common malignant tumors of male urogenital system, and the incidence of prostate cancer in China has increased significantly in the past decade. At present, endocrine therapy based on androgen blockade is the main method of clinical treatment except radical surgery and radiotherapy/chemotherapy for prostate cancer. However, the clinical benefit can only be obtained in the early stage of treatment, and nearly 90% of patients will develop to the castration resistance, and among them, nearly 90% of patients will have bone metastasis. The quality of life decreases sharply with the progression of disease for patients. In addition to the androgen signal pathway, studies have shown that many other oncogenic signal pathways have involved in the development of castration resistance, including classic cancer signaling pathways, immune and inflammatory signaling pathways, etc. Understanding the mechanism of androgen independent signal pathway in the formation of castration resistance will help to understand the off-target effect of androgen blocking therapy and introduce new treatment targets or strategies to get rid of the "no drug available" dilemma for clinical treatment of castration resistance.

Three hundred and twenty-one bacteria strains were obtained from rice leaves,stem,root tissue and paddy field soil,of which the number of strains which can inhibit mycelium of Magnaporthe grisea growth markedly was fifty-seven through fermentation in 2.0 mL Eppendorf tube,and among these fifty-seven strains,five strains were strongly antagonistic to Magnaporthe grisea.These five strains was identified for their morphologic,physiological and biochemical characteristics,and the results showed that one strain(No.156)was bacillus subtilis,two strains(No.171 and No.177)were Bacillus pumillus and two strains(No.192 and No.279)were Bacillus ploymyxa.

Objective To evaluate the clinical efficacy of interventional occlusion of ventricular septal rupture (VSR) complicating acute myocardial infarction (AMI). Methods Six patients with VSR complicated after AMI underwent transcatheter interventional occlusion in Chinese PLA General Hospital between May 2009 to May 2015 were retrospectively analyzed. Their clinical features, interventional treatment protocols, and occurance of postoperative complications were studied. Results Among the 6 patients, VSR were successfully occluded in 5 patients. One patient failed the operation due to instability of occluder after it was deployed and the occluder was retrieved. The paitents died of heart failure 6 months later. Among the 5 patients with successful closure, 4 patients presented mild residual shunt after occlusion and acute left heart failure occurred in 1 patient after operation. Two patients died during hospital stay after operation. Between them, one patient died 3 hours after operation because of cardiac tamponade and the other patient died of cardiogenic shock after withdrawal from IABP. Three patients were followed up until now and follow up echocardiography showed satisfactory cardiac function without heart failure. Conclusions Transcatheter occlusion was a reliable therapy for patients with ventricular septal rupture complicated in acute myocardial infarction which could improve cardiac function and reduce mortality.