The quality of tutors will affect the quality of graduate student education,The ar-ticle introduced the function of tutors and the rationalization of building the structure of tutors’ team,and so on,and discussed some problems which should be copied with in combination with the teaching feature in Capital Medical University,

Adult ; Ear Canal ; pathology ; Ear Neoplasms ; Female ; Humans ; Neurofibromatoses

Aged ; Female ; Foreign Bodies ; pathology ; Humans ; Laryngeal Diseases ; Larynx ; pathology ; Vestibule, Labyrinth

With the rapid development of pharmacogenetics, more and more studies have shown evidence in the association between polymorphisms at the human leukocyte antigen (HLA) loci and severe adverse drug reactions (SADRs). Several HLA-B alleles proved to be associated with SADRs for drugs such as carbamazepine, allopurinol, lamotrigine, and lfucloxacillin. hTe USA Food and Drug Administration (FDA) has even recommended routine screening for HLA-B allele before the use of abacavir and carbamazepine. With the completion of human genome project and the Hapmapproject, several new pharmacogenetics approaches such as genome-wide association study (GWAS) have emerged. hTese newly developed methods will undoubtedly accelerate the identiifcation and clinical utilization of the pharmacogenetic biomakers. In addition, the immunogenetic mechanisms by which the HLA alleles cause SADRs are explored at the cellular and molecular level. hTis review focuses on the recent progresses in HLA alleles and ADRs regarding both the clinical translation and modern pharmacogenetic methods.

Objective To investigate the mechanisms of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) combined with Triptolide in inducing the apoptosis of pancreatic cancer cells.Methods (1) The pancreatic cancer cells (MiaPaca-2 cells) were divided into 4 groups:blank control group (no drugs were added),TRAIL + Triptolide-group (only TRAIL was added),TRAIL-Triptolide + group (only Triptolide was added) and TRAIL+ Triptolide+ group (TRAIL and Triptolide were added).The vitality of cells in all the 4 groups was assessed by CCK-8.The expressions of poly ADP-ribose polymerase (PARP),cysteinyl aspartate specific proteinase-3 (Caspase-3) and Caspase-8 were detected by Western blot.The vitality of cells was detected by CCK-8 and the vitality of Caspase-8 was detected by Caspase-Glo assays after adding Z-IETD-FMK,a specific inhibitor of Caspase-8.The expressions of myeloid cell leukemia-1 (Mcl-1),Bcl-xL and Bcl-2 were detected by Western blot.(2) The MiaPaca-2 cells were divided into 8 groups:①TRAIL-Mcl-1 siRNA-group (no TRAIL was added and Mcl-1 siRNA cells were not transfected),TRAIL+ Mcl-1 siRNA-group (TRAIL was added and Mcl-1 siRNA cells were not transfected),TRAIL-Mcl-1 siRNA + group (TRAIL was not added and Mcl-1 siRNA cells were transfected)and TRAIL+ Mcl-1 siRNA+ group (TRAIL was added and Mcl-1 siRNA cells were transfected).②TRAIL-Bcl-xL siRNA-group (TRAIL was not added and Bcl-xL siRNA was not transfected),TRAIL+ Bcl-xL siRNA-group (TRAIL was added and Bcl-xL siRNA was not transfected),TRAIL-Bcl-xL siRNA + group (TRAIL was not added and Bcl-xL siRNA was transfected) and TRAIL+ Bcl-xL siRNA+ group (TRAIL was added and Bcl-xL siRNA was transfected).The vitality of the cells in all the groups was detected by CCK-8.The expressions of Caspase-3 and Caspase-8 protein were detected by Western blot.The measurement data with normal distribution were presented as (x) ± s.The comparison among groups was done by ANOVA,and the pairwise comparison was done by LSD-t test.Results (1) The vitalities of MiaPaca-2 cells in the blank control group,TRAIL + Triptolide-group,TRAIL-Triptolide + group and TRAIL + Triptolide + group were 100.0％ ± 1.1％,81.2％ ± 2.3％,78.6％ ± 3.6％and 40.1％ ± 2.5 ％,and the relative expressions of PARP protein were 0.510 ± 0.028,0.720 ±0.072,1.250 ±0.023 and 2.560 ± 0.220,the relative expressions of Caspase-3 were 0.080 ± 0.004,0.080 ± 0.003,0.110 ±0.005 and 2.720 ± 0.003,and the relative expressions of Caspase-8 were 0.070 ± 0.003,0.080 ± 0.005,0.120 ±0.003 and 0.990 ± 0.006,with significant differences among the 4 groups (F =203.607,1 457.785,332 421.900,35 437.218,P ＜ 0.05).The vitality of M iaPaca-2 cells in the TRAIL + Triptolide + group was significantly different from those in the blank control group,the TRAIL + Triptolide-group and the TRAIL-Triptolide + group (t =34.583,355.936,36.271,P ＜ 0.05).The relative expression of PARP protein of MiaPaca-2 cells in the TRAIL+ Triptolide + group was significantly different from those in the blank control group,TRAIL+ Triptolidegroup and TRAIL-Triptolide + group (t =591.784,63.739,2 268.987,P ＜ 0.05).The relative expression of Caspase-3 protein of the MiaPaca-2 cells in the TRAIL + Triptolide + group was significantly different from those in the blank control group,the TRAIL + Triptolide-group and theTRAIL-Triptolide + group (t =3 266.153,9 145.228,1 738.713,P ＜0.05).The relative expression of Caspase-8 protein of the MiaPaca-2 cells in the TRAIL+ Triptolide +group was significantly different from those in the blank control group,the TRAIL+ Triptolide-group and the TRAIL-Triptolide + group (t =663.953,l 432.878,327.584,P ＜ 0.05).The vitality of caspase-8 in the TRAIL+ Triptolide+ group was 711.0％ ± 5.1％ before adding Z-IETD-FMK,and then the vitality of MiaPaca-2 cells and caspase-8 changed to 70.0％ ± 4.8％ and 73.0％ ± 2.4％,with significant differences (t =17.956,55.027,P ＜ 0.05).The relative expressions of Mcl-1 protein in the blank control group,the TRAIL + Triptolidegroup,the TRAIL Triptolide + group and the TRAIL + Triptolide + group were 1.68 ± 0.22,2.08 ± 0.11,0.73 ±0.15 and 0.58 ± 0.18,the relative expressions of Bcl-xL protein were 0.65 ± 0.03,0.47 ± 0.03,0.32 ± 0.03and 0.26 ±0.05,the relative expressions of Bcl-2 protein were 0.65 ± 0.03,0.67 ± 0.03,0.62 ± 0.05 and 0.67 ± 0.03,with significant difference among the 4 groups (F =55.178,88.683,3.411,P ＜ 0.05).The relative expressions of Mcl-1 protein of the MiaPaca-2 cells in the TRAIL-Triptolide + group and the TRAIL+ Triptolide +group were significantly different from those of the blank control group (t =23.506,47.631,P ＜ 0.05) and the TRAIL + Triptolide-group (t =58.457,37.115,P ＜ 0.05).The relative expressions of Bcl-xL protein of the MiaPaca-2 cells in the TRAIL-Triptolide + group and the TRAIL + Triptolide + group were significantly different from those of the blank control group (t =38.105,42.219,P ＜ 0.05) and the TRAIL + Triptolide-group (t =32.476,15.814,P ＜ 0.05).The relative expressions of Bcl-2 protein in the TRAIL-Triptolide + group and the TRAIL+ Triptolide + group were not significantly different from those of the blank control group (t =4.724,1.732,P > 0.05) and the TRAIL + Triptolide-group (t =3.464,0.000,P ＞ 0.05).(2) The vitalities of MiaPaca-2 cells of the TRAIL-Mcl-1 siRNA-group,TRAIL + Mcl-1 siRNA-group,the TRAIL-Mcl-1 siRNA + group and the TRAIL + Mcl-1 siRNA + group were 100.0％ ± 2.2％,79.3％ ± 1.8％,71.2％ ± 3.2％ and 37.3％ ± 5.4％,the relative expressions of Caspase-8 protein were 0.100 ± 0.003,0.100 ± 0.005,0.100 ± 0.003 and 0.350 ±0.005,and the relative expressions of Caspase-3 protein were 0.020 ± 0.003,0.060 ± 0.003,0.020 ± 0.003 and 0.590 ±0.004,with significant differences among the 4 groups (F =136.681,2 717.391,44 471.429,P ＜0.05).The vitality of MiaPaca-2 cells of the TRAIL + Mcl-1 siRNA + group was significantly different from those in the TRAIL-Mcl-1 siRNA-group,the TRAIL + Mcl-1 siRNA-group and the TRAIL-Mcl-1 siRNA + group (t =33.937,20.207,26.689,P ＜ 0.05).The relative expression of Caspase-8 protein of the TRAIL + Mcl-1 siRNA +group was significantly different from those in the TRAIL-Mcl-1 siRNA-group,the TRAIL + Mcl-1 siRNA-group and the TRAIL-Mcl-1 siRNA + group (t =216.506,433.013,144.338,P ＜ 0.05).The relative expression of Caspase-3 protein of the TRAIL + Mcl-1 siRNA + group was significantly different from those in the TRAIL-Mcl-1 siRNA-group,the TRAIL + Mcl-1 siRNA-group and the TRAIL-Mcl-1 siRNA + group (t =329.09,458.993,987.269,P ＜0.05).The vitalities of MiaPaca-2 cells of the TRAIL-Bcl-xL siRNA-group,the TRAIL+ Bcl-xL siRNA-group,the TRAIL-Bcl-xL siRNA + group and the TRAIL+ Bcl-xL siRNA + group were 100.0％ ± 2.3％,87.2％ ± 4.1％,74.1 ± 3.7％ and 56.3％ ± 5.4％,and the relative expressions of Caspase-3 protein were 0.060 ±0.004,0.070 ± 0.003,0.060 ± 0.004 and 0.390 ± 0.003,with significant differences among the 4 groups (F =70.074,4 643.478,P ＜ 0.05).The vitality of MiaPaca-2 cells of the TRAIL + Bcl-xL siRNA + group was significantly different from those in the TRAIL-Bcl-xL siRNA-group,the TRAIL+ Bcl-xL siRNA-group and the TRAIL-Bcl-xL siRNA + group (t =24.416,41.170,18.136,P ＜ 0.05).The relative expression of Caspase-3 protein of the TRAIL + Bcl-xL siRNA + group was significantly different from those in the TRAIL-Mcl-1 siRNA-group,the TRAIL + Mcl-1 siRNA-group and the TRAIL-Mcl-1 siRNA + group (t =285.788,554.256,190.526,P ＜ 0.05).Conclusion Triptolide could induce the apoptosis of MiaPaca-2 cells by inhibiting the expressions of Mcl-1 and Bcl-xL,sensitizing TRAIL and activating Caspase-8 and Caspase-3.

Objective To investigate the relationship between HLA-DRB1 alleles and vascular anomalies in infants of Han nationality in Guangxi Zhuang Autonomous Region.Methods This study included 145 infants with vascular anomalies (99 cases of hemangioma (hemangioma group) and 46 cases of vascular malformation (vascular malformation group)) and 105 healthy infants (control group) of Han nationality residing in Guangxi Zhuang Autonomous Region.The genotypes of HLA-DRB1 alleles were determined by using PCR-sequence specific primers (PCR-SSP).Chi-square test was performed to analyze the difference in the frequency of HLA-DRB1 alleles between these groups by using the SPSS 16.0 software.Results There were significant differences in the frequency of HLA-DRB1*0901,*1401 and *16 alleles among the hemangioma group,vascular malformation group and control group (x2 =13.05,12.79,10.36,respectively,all P ＜ 0.01).Paired comparison revealed significant differences in the frequency of HLA-DRB1*0901 allele between the hemangioma group and vascular malformation group (RR =4.84,P ＜ 0.01) as well as between the hemangioma group and control group (RR =3.21,P ＜ 0.01),and in the frequency of HLA-DRB1*16 allele between the hemangioma group and control group (RR =2.25,P ＜ 0.01) as well as between the vascular malformation group and control group (RR =2.60,P ＜ 0.01).The frequency of HLA-DR*1401 allele was significantly lower in the hemangioma group than in the control group (RR =0.30,P ＜ 0.01).Conclusions HLA-DRB1*0901 and *16 may be the predisposing genes for hemangioma and vascular anomalies respectively,while HLA-DRB1*1401 appears to be protective against hemangioma,in infants of Han nationality in Guangxi Zhuang Autonomous Region.

Objective To evaluate the clinical features and renal morphological changes of the patients with urinary tract infection associated ureteral stent.Methods From Oct.2012 to May.2013,21 patients were divided into three groups depending on the different conditions:Group A (n=7):patients who had febrile urinary tract infections associated with ureteral stents; Group B (n =7):patients with ureteral stents but no fever; Group C (n=7):patients who had febrile urinary tract infections but no ureteral stent.The clinical data,laboratory data and 99Tcm-dimercaptosuccinic acid (DMSA) renal scintigraphy results were recorded prospectively and analyzed.Results In Group A,there were two patients had flank pain and positive costovertebral angle percussion tcnderness.The mean value of white blood cells and Hs-CRP of Group A and Group C were obviously higher than Group B (P＜0.05).The ratios of pyuria were 100.0％,71.4％ and 100.0％ in Group A,B and C.The ratios of positive urine bacteuria culture were 100.0％,42.9％ and 100.0％ in Group A,B and C.The results of 99Tcm-DMSA renal scintigraphy demonstrated the decreased uptake in the different portion of the kidneys on the sides of ureteral stents inserted in all the patients in Group A but no such changes in Group B and Group C.Conclusions 99Tcm-DMSA renal scintigraphy can be used to judge the status of urinary tract infection associated ureteral stent.The febrile urinary tract infection associated with ureteral stents always means pyelonephritis occurs and prompt treatment must be given.

Objective To evaluate non operative and simple operative managements of the calcaneal fractures. Methods 97 patients with calcaneal fractures were treated by non operative management or percutaneous reduction with wires or screw fixation from April 1997 to December 2001 in our department. They were followed up for more than 2 years. 64 patients were treated with non operation, 27 were fixed with wires and 6 with screws. Results 23 patients had excellent results, 67 good, 5 fair and 2 poor. The total good and excellent rate was 92.7%. 2 patients experienced secondary arthrodesis 1 year after injury. Conclusion Although the calcaneal fractures can be treated satisfactorily with non operative management or percutaneous reduction with wires or screws fixation, further prospective and comparative studies should be done in clinic to determine whether the calcaneal fractures should be treated with open reduction and fixation or with simple operative management.

Objective To explore the surgical safety and clinical efficacy of combined anterograde and retrograde method exposing porta hepatis for the treatment of the intrahepatic cholangiocarcinoma invading porta hepatis.Methods The retrospective descriptive study was conducted.The clinicopathological data of 3 patients with left intrahepatic cholangiocarcinoma invading porta hepatis who were admitted to the Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine from February 2015 to May 2016 was collected.All the 3 patients underwent left hemihepatectomy combined with caudate lobectomy after preoperative lab and imaging examinations and the evaluations of liver function and residual liver volume.The surgical procedures followed as:anterograde dissection of porta hepatis,exposure of hilar plate,left hemihepatectomy combined with caudate lobectomy,right artery resection and reconstruction,hilar cholangioplasty and bilioenteric anastomosis.Observation indicators included:(1) surgical situations:operation time,time of hepatic artery~ anastomosis and volume of intraoperative blood loss;(2) postoperative pathological examinations;(3) postoperative situations:postoperative complications (biliary fistula,hemorrhage,abnormal liver function,gastroplegia) and postoperative chemotherapy;(4) follow-up:postoperative patients' survival and carcinoma occurrence.Follow-up was performed to by outpatient examination up to December 2016.The follow-up included clinical symptoms such as abdominal pain,chills,fever and jaundice,liver function and tumor marker examination,and color ultrasound Doppler or abdominal enhanced computed tomography (CT) was performed to detect carcinoma recurrence.Measurement data was represented as average (range).Results (1) Surgical situations:all the 3 patients underwent successful left hemihepatectomy combined with caudate lobectomy using combined antegrade and retrograde method exposing porta hepatis,including 1 combined with right hepatic artery resection and reconstruction,without perioperative death.The average operation time,average time of hepatic artery anastomosis and average volume of intraoperative blood loss of 3 patients were 493 minutes (range,430-570 minutes),11 minutes and 526 mL (range,450-600 mL),respectively.(2) Postoperative pathological examination showed 3 patients were diagnosed with cholangiocarcinoma,2 with nerve bundles invaded and 2 with No.12 lymph node metastasis,with negative margins of bile duct and hepatic artery.(3) Postoperative situations:3 patients are not complicated with biliary fistula and gastroplegia.One patient with postoperative liver dysfunction after right artery resection and reconstruction underwent anti-infection,hepatoprotection and anti-hepatic encephalopathy therapies,and then was improved and discharged from hospital at 4 weeks postoperatively.The other 2 patients recovered steadily without complications such as hypohepatia,and then respectively discharged from hospital at 17 and 20 days postoperatively.All the 3 patients underwent chemotherapy of gemcitabine combined with S-1 for 8 courses at week 4 or 5 postoperatively.(4) Follow-up:all the 3 patients were followed up for 7-20 months,with good general conditions and normal liver function and without cholangitis symptoms.One patient received right artery reconstruction,and CT reexamination at postoperative month 3 showed fine imaging of right hepatic artery.There was no sign of carcinoma recurrence.Conclusion The combined anterograde and retrograde method exposing porta hepatis for the treatment of the intrahepatic cholangiocarcinoma invading porta hepatis can increase the radical resection rate and surgical safety.

OBJECTIVE:To evaluate the economics of caspofungin vs. voriconazole in initial empirical antifungal therapy of fe-brile neutropenia(FN). METHODS:Based on two international multiple center clinical trials about caspofungin vs. voriconazole in initial empirical antifungal therapy of FN,combined with domestic clinical experts'opinions about drug selection,a decision tree model was developed. TreeAge Pro 2011 software was used to analyze the cost and effectiveness of 10-day therapy of caspofungin or voriconazole as initial empirical antifungal therapy. RESULTS:The direct medical cost of caspofungin group was lower than that of voriconazole group(52826.71 yuan vs. 58246.70 yuan). The success rate and survival rate were higher than voriconazole group(33.95% vs. 25.63%、92.36% vs. 91.87%). Whether the success rate or the survival rate of patients as the effect indicators, cost-effectiveness ratio of caspofungin group was lower than that of voriconazole group. Moreover,incremental cost effectiveness ra-tio and sensitivity analysis confirmed this conclusion. CONCLUSIONS:Caspofungin has more advantages than voriconazole in cost and effectiveness as initial empirical antifungal therapy in patients with FN.