As a characteristic tumor therapy in China, Chinese medicine (CM) plays an important position in comprehensive treatment of tumor. It's a critical issue of objective realization, analysis and evaluation of CM safety for scientific decision-making in tumor safe medication and it also is a pivotal issue which affects the international communication. The safety evaluation of CM includes three phases: pre-clinical safety evaluation, clinical trials (micro-dose studies and traditional clinical trials) and post-marketing CM safety assessment. The key point of evaluation should be distinguished among different stages and various types of CM (such as classic formulas, Chinese herbal extracts, etc). Emphasis should be given to chronic toxicity when evaluating oral Chinese herbal , microdose studies and quality control must be underlined while injection is evaluated and more attention should be pay to the dose-effect relationship and time-effect relationship when turned to toxic Chinese medicine , and so as for the toxicity grading study. Moreover, we should constantly improve CM safety assessment method in various stages of tumor treatment, such as introducing the concept of syndrome classification theory, bringing in metabonomics and real-world research method which are similar to the CM therapeutic concept. Most importantly, we must keep its own feature of CM theory when we learn the concept of safety evaluation from abroad. Actively exploring the anti-tumor medicine safety evaluation methods and strategies is of great significance for clinical and experimental research, and it can provide supportability platform to CM's international communication.
Animals ; Combined Modality Therapy ; Humans ; Medicine, Chinese Traditional ; adverse effects ; methods ; Neoplasms ; therapy ; Safety

The article discusses a number of important marketing ideas which should be clarified and fully understood in strengthening the follow-up management of patients,including understanding of the meaning of customers,the formation of the concept of market and the evolution of marketing.The adoption of patient follow-up management could delivered value to customers and promote their satisfaction.In the end,the article proposes that a long-term marketing mechanism of patient follow-up services should be established in order to achieve the a better development of hospitals.

OBJECTIVETo explore significance of preoperative color Doppler flow imaging (CDFI) for screening deep vein thrombosis in upper limbs fracture.

METHODSFrom January 2009 to December 2011, 1200 patients with upper limb fracture caused by trauma were respectively analyzed. There were 833 males and 367 females,ranging from 20 to 78 (mean 41.94 +/- 15.41) years. All patients had swelling and pain in injured limbs when enrolled. CDFI was used to examine upper limbs vein at 3 to 10 d after improvement of swelling, 1 day before reduction. Relationship among occurrence of thrombosis, gender, age and fracture sites were analyzed. Patients with DVT were analyzed with respective study to decide whether combined with diabetes, hypertension and hyperlipidemia.

RESULTSAll patients were checked by CDFI,which confirmed 9 cases with DVT. The rate of thrombosis was 0.75%, women than men (P < 0.01). The risk of blood clots occurred over 30 years, and the occurrence of thrombosis in humerus fracture was higher than radius ulnar fracture. One of 9 patients combined with hypertension and hyperlipidemia, 1 case combined with diabetes, and 7 cases with no complication.

CONCLUSIONUpper trauma fracture may occur deep vein thrombosis; CDFI should be used to check DVT in qualified hospital,which can maintain medical safety,decrease occurrence of medical disputes, and ganrantee patient's safety.

Adult ; Aged ; Aged, 80 and over ; Diabetes Complications ; surgery ; Female ; Fractures, Bone ; complications ; surgery ; Humans ; Hypercholesterolemia ; complications ; Hypertension ; complications ; Male ; Middle Aged ; Preoperative Period ; Ultrasonography, Doppler, Color ; Upper Extremity ; injuries ; Venous Thrombosis ; complications ; diagnostic imaging ; Young Adult

Objective To assess the effect of three different liver vascular exclusions on prognosis of patients undergoing hemihepatectomy.Methods Clinical data of 216 patients undergoing hemihepatectomy were analyzed retrospectively.Ninety-eight out of 216 patients received Pringle maneuver during hepatectomy in group A,71 patients of selective liver inflow and outflow vascular exclusions in group B,47 patients using liver hanging maneuver combining with selective liver inflow and outflow vascular exclusions were in group C.Results There was no difference in operation time between the three groups ( t =0.72,0.83,and 0.67,P ＞ 0.05 ).The intraoperative blood loss and transfusion in group B and C were less than that in group A (t =3.72,3.83 and 4.11,4.07,P ＜0.05).Serum albumin level on day 1 and day 3 in group B and C were higher than that in group A (t =3.65,3.77,and 3.90,3.74,P ＜0.05 ).Serum total bilirubin level on day 3 and 5 in group B and C were lower than that in group A ( t =4.13,5.01,and 4.09,3.99,P ＜0.05).Serum alanine aminotransferase on day 1,3 and 5 in group B and C were lower than that in group A ( t =5.36,6.14,and 5.70,7.01,and 4.94,3.98,P ＜ 0.05 ).Postoperative complication rate in group A was higher than that in group B and C ( x2 =13.71 and 23.56,P ＜ 0.05 ).The 3-year survival rate of patients with malignant tumor in the three groups were not significantly different (t =2.38,P ＞ 0.05 ).Conclusions Intraoperative blood loss and transfusion and postoperative complication rate can be reduced,and liver injury can be diminished in hemihepatectomy using selective liver inflow and outflow vascular exclusion alone and or in combination with a liver hanging maneuver.

Objective To investigate the brain protective effect of isoflurane preconditioning on the rat liver against ischemia-reperfusion through determining the content of S-100β protein in peripheral blood in combination with mitochondrial ultrastructure in rat brain.Methods A total of 45 SD rats were randomly divided into three groups,sham group (group S):the only separation of the hepatoduodenal ligament,but did not block the hepatic portal blood supply; ischemia-reperfusion group (group I/R):liver ischemia 60min,reperfusion 120 min; isoflurane preconditioning group (group ISO):60 min before liver I/R,ISO pretreatment for 30 min,elution in the air after 30 min; 24 h after recirculation the forebrain tissues were rapidly removed.The changes of mitochondrial ultrastructure were observed by electron microscopy.The content of S-100β protein in serum was measured before ischemia and reperfusion 120 min through the application of Elisa kit.Results Marked swelling of mitochondria with disrupted cristae and damaged matrix were observed in group I/R,while relative intact mitochondria were seen in sham and ISO groups.The content of S-100β protein in serum was significantly higher in I/R group [(1.52 ±0.26) μg/ml] than in sham [(0.31 ±0.05)μg/ml] and ISO [(0.79 ± 0.21) μg/ml] groups (P ＜0.05).Conclusions The liver ischemia-reperfusion may injure the brain of the rat and isoflurane preconditioning can protect the rat brain from injury.

Objective To compare the perioperative outcomes and short-term efficacy of three-port extraperitoneal laparoscopic radical prostatectomy (ELRP) and four-port ELRP.Methods Two hundred patients who had undergone ELRP for prostate cancer by a single surgeon from November 2010 to October 2014 were retrospectively analyzed.Among them,95 cases underwent three-port ELRP and 105 cases underwent four-port ELRP.On the basis of traditional four-port ELRP,three-port ELRP was characterized by the omission of the trocar on the inner side of right anterior superior iliac spine.The mean age was 66.8 ± 15.5 years,and mean total prostate specific antigen (tPSA) was 15.3 ± 12.4 μg/L.There were no significant differences including age,body mass index,tPSA,clinical stages,acceptance of neoadjuvant hormone therapy,history of transurethral resection of the prostate,history of diabetes mellitus between the 2 groups (P ＞ 0.05).Patients in three-port ELRP group had significantly smaller prostate volume than fourport group (35.6 ± 16.7 ml versus 42.2 ± 24.7 ml,P ＜ 0.05).The clinical factors as operative time,estimated blood loss,hospital stay,drainage tube keeping days,pathological Gleason scores,pathological stages,positive surgical margin rates,biochemical recurrence rates and urinary incontinence rates were compared between the 2 groups.Results The three-port group had significantly shorter operative time than the four-port group (81.0 ± 18.6 min versus 103.6 ±34.6 min),less estimated blood loss (102.6 ±75.8 ml versus 217.5 ± 182.9 ml),less positive surgical margin rates (13.7％ versus 27.6％).There were 9 patients having Gleason scores more than 7 in the three-port ELRP group and 29 patients in four-port ELRP group (P ＜ 0.05).There were no significant differences of hospital stay,drainage tube keeping days,pathological stages between the 2 groups (P ＞ 0.05).Eighty-three cases in the three-port ELRP group (87.4％) were followed up for 5-19 months with the median time of 11 months.Ninety-two cases in fourport ELRP group (87.6％) were followed up for 17-52 months and the median time was 27 months.There were no significant differences of biochemical recurrence rates and urinary incontinence rates between the 2 groups(P ＞ 0.05).Conclusions Compared to four-port ELRP,three-port ELRP can provide shorter operative time,less blood loss,better negative surgical margin rates,similar oncological control and recovery of postoperative continence.In experienced hands,three-port ELRP could be a feasible and effective option for localized prostate cancer.

Objective To evaluate the learning curve of three-port extraperitoneal laparoscopic radical prostatectomy(ELRP) and to minimize operative time and blood loss about this procedure.Methods From August 2013 to October 2014,the data from 95 consecutive patients,who had undergone three-port ELRP for prostate cancer,were retrospectively analyzed.The mean age was 65.9 ± 7.7 years,mean total PSA level was 15.4 ± 12.7 μg/L,and mean body mass index(BMI) was 24.8 ± 3.2 kg/m2.According to the number of procedures performed by the surgeon,all patients were classified into three chronologic groups,including group A (No.1-32),group B (No.33-64) and group C (No.65-95).There were no significant differences including age,BMI,tPSA,estimated prostate volume,clinical stages,history of neoadjuvant endocrine therapy,history of transurethral resection of the prostate (TURP) among group A,B and C (P ＞ 0.05).The operative outcomes analyzed were operative time,estimated blood loss,hospital stay,drainage tube indwelling days,pathological Gleason scores,pathological stages,positive surgical margin rates,biochemical recurrence rates and urinary incontinence rates.Among these 95 patients,the results of the first 32 cases were compared with those of the remaining 63 cases,the first 64 with the remaining 31.Results The average operative time in 95 patients was 81.0 ± 18.6 min.The sloping learning curve for this surgeon showed that the operative time for all 95 cases was strongly correlated with additional experience (| rs | =0.612,P＜0.01).Operative time,however,was not strongly correlated with the surgeon's experience in each group of A,B and C(P ＞0.05).Group A had longer operative time than that of Group B plus C(96.4 ± 11.3 min vs 73.2 ± 16.7 min,P ＜0.01).Group A plus B had longer operative time than that of group C (87.6 ± 17.2 min vs 67.5 ± 13.8 min,P ＜ 0.01).For all cases,the estimated blood loss was strongly correlated with additional experience (| rs | =0.677,P ＜ 0.01).Estimated blood loss was strongly correlated with the accumulation of experience for the initial 32 cases(| rs | =0.619,P ＜ 0.01).However,no strong correlation was observed over the next 63 cases.Group A had more blood loss than that of Group B plus C (158.7 ± 81.3 ml vs 74.1 ± 54.4 ml,P ＜ 0.01).Group A plus B had more blood loss than that of group C (125.5 ± 71.6 ml vs 55.3 ± 61.6 ml,P ＜ 0.01).But hospital stay,drainage tube keeping days were not strongly correlated with additional experience in each group(P ＞ 0.05).There were no significant correlation between the accumulation of experience and positive surgical margin rates,biochemical recurrence rates and urinary incontinence rates.Conclusion Our experience of three-port ELRP cases appears to be favorable with decreasing tendency in operative time,estimated blood loss with experience accumulation.Exposure to 32 surgeries,operative time and estimated blood loss reduced significantly,and after 64 cases operative time and estimated blood loss further reduced.

OBJECTIVE To discover a small-molecule bromodomain-containing protein 4 (BRD4) inhibitor that induces AMP- activated protein kinase- modulated autophagy- associated cell death in breast cancer and exploreits potential mechanisms. METHODS BRD4 interactors were analyzed by PPI network prediction and The Cancer Genome Atlas (TCGA) analysis. The interaction between BRD4 and AMPK was confirmed by co- immunoprecipitation assay. Novel BRD4 inhibitors were designed and synthesized based upon pharmacophore analysis of BRD4 (1), then screened by anti-proliferative activity and Alpha Screen of BRD4 (1). The selectivity of the best candidate compound 8f was validated by co-crystallization, FRET assay and co-immuno precipitation assay. The mechanisms of 8f were investigated by fluorescence microscopy, electron microscopy, Western blotting, immunocy?tochemistry, siRNA and GFP-mRFP-LC3 plasmid transfections, as well as immunohistochemistry and immunofluorescence. Potential mechanisms were discovered by iTRAQ- based proteomics analysis and the therapeutic effect of 8f was assessed by xenograft breast cancer mouse and zebrafish models. RESULTS We identified that BRD4 interacted with AMPK, which was remarkably downregulated in breast cancer. We next designed and synthesized 49 candidate compounds, and eventually discovered a selective small-molecule inhibitor of BRD4 (8f). Subsequently, 8f was discovered to induce autophagy-associated cell death (ACD) by BRD4- AMPK interaction, and thus activating AMPK- mTOR- ULK1-modulated autophagic pathway in breast cancer cells. Interestingly, the iTRAQ- based proteomics analyses revealed that 8f induced ACD pathways, involved in HMGB1, VDAC1/2 and eEF2. Moreover, 8f displayed a therapeutic potential on both xenograft breast cancer mouse and zebrafish models. CONCLUSION We discovered a novel small-molecule inhibitor of BRD4 that induces BRD4-AMPK-modulated ACD in breast cancer, which may provide a candidate drug for future cancer therapy.

Objective:To investigate the effects of deep hypothermia on MAC,cardiac anesthetic index and myocardial stability of valotile anesthetics. Method: Forty New Zealand white rabbits were randomly divided into 4 groups:halothane, enflurane,isoflurane and sevoflurane. MAC of valotile agents were determined with the test of clamping tail at normal(38 C?0.5 C )and deep hypothermic(23 C?0.5 C )temperatures. The end-tidal valotile agent concentration at which ventricular arrhythmia appeared by increasing valotile agent concentration and stimulating the heart with extrathoracic electric shock(25V 50Hz)were recorded. Result:MAC of halothane, enflurane,isoflurane and sevoflurane were decreased by average percentage of 5.1,3.6,4.4 and 4.3 per degree from 38 C to 23 C respectively. Cardiac anesthetic indexes during deep hypothermia were 4.4,3.18.6.25 and 4.6. There was significantly higher incidence of ventricular fibrilation in halothane and enflurane groups (100％) than that in isoflurane and sevoflurane groups(40％)under 8 MAC anesthetics. Conclusion:Isoflurane is the most suitable valotile agent for deep hypothermic anesthesia, while enflurane is the least.