Objective To study the antibacterial mechanisms of berberine and try to understand the reasons why bacteria cells difficultly resisted to it. Methods Detecting the minimal inhibitory concentration (MIC) of bacterial cultures incubated under sub-MIC concentration of berberine, Huanglian, and Neomycin for more than 200 generations, in order to analyze the bacteria resistance. Detecting the binding kinetics of berberine to DNA, RNA, and proteins. Observing the changes in bacterial cell surface structure with scanning electron microscopy. Detecting the Ca2+ and K.+ released from berberine-treated bacterial cells with atomic absorption spectrum. Detection the absorption of methyl-3H-thymine (3H-dT), 3H-uridine (3H-U), and 3H-tyrosine (3H-Tyr) into berberine-treated bacterial cells. Results MICs of bacterial cultures, growing more than 200 generations in MH medium with 1/2 MIC of berberine (BA200) or Huanglian (HA200), did not increase compared to the control, while remarkably increased in MH medium with 1/2 MIC of Neomycin (NA200). In addition, from the culture NA200 it was easy to isolate resistant mutant strains which could grow in MH medium with more than four times MIC Neomycin, but from the culture BA200 and HA200 it was difficult to isolate berberine or Huanglian mutant strains could grow in MH medium with more than four times MIC berberine or Huanglian. The binding kinetics of berberine to DNA, RNA, and proteins illustrated that berberine could easily and tightly bind to DNA and RNA, and hardly dis-bind from DNA- and RNA-berberine complexes. Berberine could easily bind to protein too, but also easily dis-bind from berberine-protein complex. The bacterial cells treated with berberine sharply decreased the absorption of 3H-dT, 3H-U, and 3H-Tyr, as the radioactive precursors of DNA, RNA, and protein biosynthesis. Berberine could damage bacterial cell surface structure, especially for Gram-negative bacteria. Ca2+ and K+ released from berberine-treated cells increased significantly compared to the control. Conclusion All of above results indicate that bacterial cells could not easily become resistant mutants to berberine. The mechanisms for the bactericidal effect of berberine include: inhibiting DNA duplication, RNA transcription, and protein biosynthesis; influencing or inhibiting enzyme activities; destructing the bacterial cell surface structure and resulting in Ca2+ and K+ released from cells. All of the berberine bactericidal mechanisms are the most essential physiological functions for a live cell, if influenced any one such function, the mutation would be lethal mutation, so that it is difficult to get berberine resistant cells. The results in this paper also prefigure that berberine and its related Chinese medicines would provide a feasible way to control antibiotic resistance problem.

OBJECTIVE:To systematically review the efficacy of Qijiao shengbai capsule in the adjuvant treatment of leukope-nia,and provide evidence-based reference for the clinical treatment. METHODS:Retrieved from CJFD,VIP,Wanfang Database and Medline and EMBase,randomized controlled trials(RCT) about the efficacy of Qijiao shengbai capsule (test group) versus blank control(control group) in the adjuvant treatment of leucopenia were collected. Meta-analysis was performed by using Rev Man 5.2 software after the quality assessment and data extraction. RESULTS:A total of 15 RCTs were included,involving 1 383 patients. Results of Meta-analysis showed the total effective rate [OR=0.31,95%CI(0.23,0.43),P<0.001],obvious effective rate [OR=0.31,95%CI(0.24,0.41),P<0.001],leukocyte count [MD=-1.04,95%CI(-1.10,-0.98),P<0.001] and myelosuppres-sion reduction [OR=0.27,95%CI(0.14,0.52),P<0.001] in test group were significantly higher than control group,there were sig-nificant differences. Only 9 patients had adverse reactions of mild diarrhea,nausea and other symptoms,and it relieved after symp-tomatic treatment. CONCLUSIONS:Qijiao shengbai capsule has achieve good efficacy in the adjuvant treatment of leukopenia. Due to the limits of quality and sample size,more strict designed,long-term follow-up of large scale RCTs are needed for the fur-ther verification of the conclusion.

Aim To assay the mutagenicity of Enphorbia lunulata(EL) decoction and to modify the Ames test for evaluation the mutagenicity of herbal medicine samples.Method The mutagenicity of EL decoction was assayed by standard Ames test; the teratogenicity was done by mammalian bone marrow chromosomal aberration test. In modified Ames test system,the influence of histidine EL decoction was excluded by additional negative control, in which the test media was supplied with histidine (histidine amount equaled to the histidine in different concentration of EL decoction).Result The mutagenicity of EL decoction was positive in the standard Ames test. The teratogenicity of EL decoction was negative in mammalian bone marrow chromosomal aberration test. By the modified Ames tests,the mutagenicity of EL decoction was negative.Conclusion The standard Ames test is not suitable for evaluating the mutagenicity of EL decoction, but the modified Ames test is. The mutagenicity in vitro and the teratogenicity in vivo of EL decoction are all negative.

AIM Objective By comparing E.coli's resistance to antibiotics and Chinese medical herbs before and after incubated in LB containing Neomycin or Chinese medical herbs, we try to understand the difference in their mechanism of resistance. METHODS We incubated E.coli cells under the culturing media with low concentration of Neomycin and Chinese medicine herbs respectively; lately, the culturing process were continued under the media with no Neomycin or Chinese medicine herbs. We tested the minimal inhibitory concentrations(MIC)of Neomycin(Kanamycin, Gentamicin, Tetracyclin etc) and Chinese medical herbs to culture cells. Result The experimental data indicated that increased resistance of population cells in the broth including Neomycin happened easily, as well as multi resistance simultaneously. As for the Chinese medical herbs, the case is different. After growing in the LB containing one of Huang Lian (rhizoma coptidis), Berberine or San-Huang-Tang of low concentrations, population cells did not increase their resistance either to antibiotics or to Chinese medical herbs. Removing the pressure of Neomycin, E.coli population cells resistance came back to the initial level. CONCLUSION The increased antibiotic resistance of population cells is unstable, and alternative using of different antibiotics maybe contribute to the alleviation of antibiotics resistance.

OBJECTIVE:To systematically review the effectiveness and safety of Yinzhihuang oral liquid in the adjuvant treat-ment of neonatal jaundice,and provide evidence-based reference for clinical treatment. METHODS:Retrieved from CJFD,VIP Da-tabase,Wanfang Database,Medline and EMBase,randomized controlled trials(RCT)about the effectiveness of Yinzhihuang oral liquid(test group)based on the canventional treatment(control group)in the adjuvant treatment of neonatal jaundice were collect-ed,and Meta-analysis was performed by using Rev Man 5.2 software after data extracting and quality evaluating by modified Jadad. RESULTS:Totally 12 RCTs were enrolled,involving 1585 patients. Results of Meta-analysis showed total effective rate [OR=0.19,95%CI(0.12,0.30),P<0.001],serum total bilirubin levels [MD=-40.78,95%CI(-42.68,-38.89),P<0.001] and time of bilirubin decreased to normal [MD=-2.56,95%CI(-2.72,-2.40),P<0.001] in test group were significantly better than control group,the differences were statistically significant between 2 groups;3 reports of adverse reactions showed scme children had vomiting and mild diarrhea,they were improved after symptomatic treatment,and it did not affect the treatment. CONCLU-SIONS:The effectiveness of Yinzhihuang oral liquid is good in the adjuvant treatment of neonatal jaundice,with mild adverse reac-tions.

OBJECTIVE:Tosystematically evaluate the efficacy of Yixinshu capsule in the adjuvant treatmentof angina pecto-ris,and provide evidence-based reference for clinical treatment. METHODS:Retrieved from CJFD,VIP Database,Wanfang Data-base,Medline and EMBase,randomized controlled trials(RCT)about the efficacyof Yixinshu capsule(test group)versus other drugs (control group) in the adjuvant treatment of angina pectoris were collected. Meta-analysis was performed bu using Rev Man 5.2 software after data extraction and quality evaluation by modified Jadad. RESULTS:Totally 11 RCTs were enrolled,involving 1 827 pa-tients. Results of Meta-analysis showed the total effective rate of angina pectoris improvement [OR=0.30,95%CI(0.23,0.40),P<0.001] and electrocardiogram improvement [OR=0.52,95%CI(0.41,0.66),P<0.001] in test group were significantly higher than control group,there was significant difference between 2 groups. CONCLUSIONS:Yixinshu is effective for the adjuvant treatment of angina pectoris.

Objective To investigate the incidence of diabetes mellitus and risk factors for the disease in chronic pancreatitis (CP) patients.Methods A historical cohort study on subjects with painful CP who were admitted to hospital from Jan.1997 to July 2007 were conducted.A life-table method was used to estimate the cumulative probability of the development of diabetes mellitus once clinical onset of abdominal pain.Cox proportional-hazards model was used for multivariate analysis of the variables including age,sex,drinking and smoking habits,etiological factor,presence of pancreatic masses,pancreatic calcifications,measure of intervention,diarrhea,weight loss and degree of pain.Results Data were obtained from 354 patients (239 males,mean age at onset of pain (38.1±17.6) years;alcoholic origin 18.1%) with painful CP.The mean follow-up period was (45.2±32.9)months.The rate of diabetes mellitus in CP patients was 16.1%.There was a high incidence (29.8%)of diabetes mellitus 1 year before the episodes of abdominal pain.The cumulative risk of diabetes mellitus in subjects 5 and 10 years after the episodes of pain was 9.3% and 20.7%,respectively.Cox proportional-hazards model selected smoking (＞10 pack years) (hazard rate (HR)= 3.3),mild abdominal pain (HR=5.2),weight loss (HR = 2.6) and pancreatic calcifications (HR = 2.2) as variables identifying subjects with diabetes mellitus in patients with painful CP before they were performed therapeutic endoscopy or surgical intervention.Smoking (＞10 pack years) (HR = 3.0),weight loss (HR= 2.8) and distal pancreatectomy (HR =7.3) were identified with an increased risk of diabetes mellitus in these cases after they received therapeutic endoscopy or surgical intervention.Conclusion The risk factors of diabetes mellitus for CP appears to be independent of smoking (＞10 pack years),mild abdominal pain,weight loss,pancreatic calcifications and distal pancreatectomy.

OBJECTIVE:To optimize the formulation optimization of Nicorandil sustained-release matrix tablet,and evaluate its drug release properties in vitro. METHODS:Based on single factor test,powder direct compression method was used,using nicorandil cumulative release rate (Q) in 1,4,8,12 h as evaluation indexes,central composite design-response surface method was adopted to optimize the amount of hydroxypropyl methylcellulose(HPMC)and ethyl cellulose(EC);Q values within 12 h in different pH (1.0,5.0,6.8,7.4) media were compared. RESULTS:The optimized formulation (every tablet) was nicorandil 10 mg,HPMC 150 mg,EC 90 mg,microcrystalline cellulose 80 mg,lactose 60 mg,magnesium stearate 2%. Q1 h,Q4 h,Q8 h and Q12 h of the obtained formulation were 23.6%,51.3%,83.7% and 96.9%,respectively;deviation from the predicted values were 2.1%,1.6%,1.0%,0.2%. Q values were similar in pH 1.0-7.4 at different time points. CONCLUSIONS:The obtained Nicor-andil sustained-release matrix tablet by optimal formulation shows sustained-release effect,and the change of pH 1.0-7.4 has no in-terference in the release characteristics of main drug.

Objective To investigate the incidence and risk factors of pancreatic cancer in patients with painful chronic pancreatitis (CP). Methods Three hundred and ninty-seven patients with painful CP were recruited between Jan. 1997 to July 2007. A life-table method was used to estimate the cumulative probability of the incidence of pancreatic cancer. Cox proportional-hazards model was used for multivariate analysis of the variables including age, sex, drinking and smoking habits, etiological factor, presence of pancreatic masses, pancreatic calcifications, measure of intervention, diabetes mellitus, diarrhea, weight loss and degree of pain. Results Of 397 patients,346 (87.2%) were follow-up for (34.3±27.1)months with 244 males and 102 females(2.4 :1). The mean age of the patients were (47.7 ±13. 7) years and alcoholic origin accounted for 22. 2%. The incidence of the pancreatic cancer was 8.1 % (28/346). There was a high incidence of cancers during the 4 years after the episodes of abdominal pain. The cumulative risks of pancreatic cancer 1, 5 and 10 years after the episodes of pain were 5 %, 5.6% and 11.6% respectively. Cox proportional-hazards model selected age at onset (≥51 years) [hazard rate(HR) = 3. 1], pancreatic calcifications ( HR = 4.1) ,pancreatic masses ( HR = 7. 1 )], no improvement of abdominal pain ( HR = 3. 8), increased frequency of pain (HR= 6.8), no diarrhea (HR= 15.3) as variables identified with pancreatic cancer in painful CP patients. Conclusions Pancreatic cancer should be suspected in patients with CP. The risk factors of pancreatic cancer are age at onset (≥ 51 years), pancreatic calcifications, pancreatic masses, no improvement of abdominal pain, increased frequency of pain and no diarrhea.