Objective To discuss the effectiveness and safety of transarterial chemoembolization(TACE)combined with regorafenib and programmed death receptor-1(PD-1)in the second-line sequential treatment of advanced hepatocellular carcinoma(HCC).Methods The clinical data of a total of 83 patients with advanced HCC,who received TACE combined with regorafenib and PD-1(triple-therapy group)or TACE combined with regorafenib(dual-therapy group)at the Affiliated Hospital of Nantong University and Nantong Municipal Third People's Hospital of China between October 2020 and May 2022,were retrospectively analyzed.The clinical data were collected and evaluated.Modified response evaluation criteria in solid tumors(mRECIST)was used to evaluate the curative effect.The progression-free survival(PFS),overall survival(OS)and treatment-related adverse events(TRAEs)were compared between the two groups.The Kaplan-Meier method was used to draw PFS and OS curves,the Log-rank test was used to compare the relevant data between the two groups,and the COX regression model was drawn to determine the factors influencing PFS and OS.Results There were no statistically significant differences in the baseline data between the two groups(P≥0.05).In the triple-therapy group and the dual-therapy group,the objective response rate(ORR)was 31.1％and 18.4％respectively(P=0.024),and the disease control rate(DCR)was 77.8％and 57.8％respectively(P=0.038).The OS and PFS in the triple-therapy group were higher than those in the dual-therapy group(16.80 months vs 13.20 months,and 9.10 months vs.7.40 months,respectively).No statistically significant difference in the incidence of adverse drug reactions existed between the two groups(P 0.05).Conclusion In the second-line sequential treatment of advanced HCC,TACE combined with regorafenib and PD-1 is more effective than TACE combined with regorafenib,therefore,it can be used as a preferred second-line treatment for advanced HCC.

OBJECTIVETo evaluate the effect of VKORC1, CYP2C9, GGCX, PROC, EPHX1 and CYP4F2 gene polymorphisms on Warfarin maintenance dose variation in Chinese Han Population.

METHODSFour hundred eighty-eight patients with prosthetic heart valves, atrial fibrillation or pulmonary thromboembolism and achieved stable Warfarin dose were enrolled. TaqMan probe or direct sequencing were used to genotype Y9VKORC1, CYP2C9, GGCX, EPHX1 and CYP4F2 gene polymorphisms. Demographic characteristics, stable therapeutic dose of Warfarin and concomitant medications were collected for all patients. The effect of VKORC1, CYP2C9, GGCX, PROC, EPHX1 and CYP4F2 gene polymorphisms, demographic characteristics and concomitant medications on Warfarin daily maintenance dose were analyzed with statistical method.

RESULTSVKORC1 and CYP2C9 gene polymorphisms could explain more than 50% Warfarin maintenance dose variation in recruited patients, while CYP4F2 gene polymorphisms could only explain 1%. GGCX, PROC and EPHX1 gene polymorphisms had no impact no Warfarin maintenance dose. VKORC1 and CYP2C9 gene polymorphisms have a greater impact on Warfarin maintenance dose compared with demographic characteristics and concomitant medications.

CONCLUSIONVKORC1 and CYP2C9 gene polymorphisms have a significant impact on Warfarin maintenance dose in Chinese Han population.

Adult ; Aged ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; ethnology ; genetics ; Atrial Fibrillation ; drug therapy ; ethnology ; genetics ; Cytochrome P-450 CYP2C9 ; Cytochrome P-450 Enzyme System ; genetics ; Cytochrome P450 Family 4 ; Dose-Response Relationship, Drug ; Epoxide Hydrolases ; genetics ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Protein C ; genetics ; Pulmonary Embolism ; drug therapy ; ethnology ; genetics ; Treatment Outcome ; Vitamin K Epoxide Reductases ; genetics ; Warfarin ; administration & dosage ; Young Adult

Curriculum of introduction to clinical medicine(ICM) in the University of Ottawa's Faculty of Medicine was analyzed. Characteristics of ICM course in the University of Ottawa's Faculty of Medicine were: early setting, rich in content, long duration and focusing on clinical. ICM course between Guangxi Medical University and University of Ottawa's Faculty of Medicine were compared. Taking advantages of ICM course in the University of Ottawa's Faculty of Medicine was conductive to better understanding the importance , teaching objectives and means of ICM course . The teaching quality evaluation system of ICM course would be built in the future.

Objective To discuss and analyze the imaging features of extramedullary hematopoiesis (EMH).Methods Imaging data of EMH in 7 patients with 85 lesions confirmed by clinical and pathological results were retrospectively analyzed.Results CT or MRI showed thoracic paravertebral multiple tumor-like soft tissue masses in 6 patients accompanied with pleural mass in 1,with liv-er mass in 1 and spleen mass in 1,and the masses in the distal ileum and in front of the inferior vena cava in 1.Thoracic paraverte-bral and pleural masses presented isodensity on plain CT and moderate enhancement on post-contrast CT.Among the 6 liver mas-ses,CT showed uniform density in 5 and small area of necrosis in 1.The only one spleen mass also appeared inner necrosis and mul-tiple small calcifications.The mass in the ileum presented thickened bowel wall with moderate enhancement,meanwhile the mass in front of vena cava presented obvious edge enhancement.MRI in 2 patients showed the masses with low signal on T1 WI and high sig-nal on T2 WI.Conclusion EMH has certain specific imaging characteristics,which may be helpful for correct diagnosis of EMH when combined with the clinical data.

Objective To provide experimental evidence for the development of multi-epitope-baseded marker vaccines through investigating the humoral and cellular immune responses in BALB/c mice induced by the multiple antigen peptides (MAPs) with the mimic epitope.Methods Three types of MAPs in eight branched forms containing the mimic epitope of Mycoplasma genitalium adhesion protein (MgPa) were prepared using poly-lysine as the core matrix.The purity of MAPs was analyzed by reverse phase high performance liquid chromatography (RP-HPLC).The molecular weights of MAPs were characterized by Mass Spectrometry.The BALB/c mice were immunized intramuscularly for four times with single or mixed MAPs.The specific IgG antibody and the subtype of IgG antibody in serum of the immunized mice were detected by indirect ELISA.The proliferative responses of the spleen lymphocytes were detected using MTT assay.The ELISA were used to detect IFN-γ and IL-4 levels in the cultured supematant of spleen lymphocytes.Results The three types of MAPs containing the mimic epitopes were successfully prepared with high purity.They,could stimulate mice to produce specific IgG antibodies,of which,the major antibody isotype was Th1 immune response-associated IgG2a.Compared with the single MAP immunization group,the mixed-MAPs immunized mice produced more IgG,IgG1 and IgG2a antibody (P＜0.05).Furthermore,these MAPs could enhance the specific proliferation of spleen lymphocytes in immunized mice and induce the production of IFN-γ and IL-4.The levels of IFN-γand IL-4 in mixed-MAPs group were significantly higher than those of the single MAPs group (P＜0.01).Conclusion The three types of MAPs could induce strong specific cellular and humoral immune responses.The immunological competence of the mixed-MAPs was stronger than those of the single MAP.

ObjectiveTo screen a 12-mer phage display peptide library by the polyclonal antibody (pAb) against the recombinant adhesion protein of Mycoplasma genitalium (rMgPa) in order to obtain the antigenic mimic epitopes of MgPa.MethodsThe purified pAb was used to screen the immunodominant mimic epitopes of MgPa by a random 12-peptide phage display library.Seventy-four recombinant phage clones were randomly selected,and then DNA sequence analysis and computer-based bioinformatics analysis were performed to define the consensus amino acid residues of the mimotopes by MIMOX.The binding specificities of the selected phage-displayed peptides to the purified pAb were confirmed by ELISA,competitive ELISA and Western blot analysis.Results After four rounds of biopanning,a significant enrichment of phages was achieved,the inserts from 74 phage clones distinguished 45 peptides based on the different amino acids sequences.Amongst 45 peptides,36 peptides were ELISA positive and 23 peptides that absorbance values were higher than 1.5 showed high reactivities with pAb and effectively inhibited the binding of pAb to rMgPa.Immunoscreening via phage display peptide library revealed three different mimptopes of adhesion protein of M.genitalium,P-S-A-A/V-X-R-F/W-E/S-L-S-P,A-K-I/L-T/Q-X-T-L-X-L and K-S-L-S-R-X-D-X-I.Results of bioinformatics analysis by MIMOX demonstrated that S,A,F for cluster 1,A,K,I,T and L for cluster 2,K,S,L,R,D and I for cluster 3,may be the key consensus amino acid residues in the aligned mimotopes,respectively.ConclusionAntigenic mimics on MgPa were successfully identified and the motif P-S-A-A/V-X-R-F/W-E/S-L-S-P,A-K-I/L-T/Q-X-T-L-X-L and K-S-L-S-R-X-D-X-I may represent the immunodominant mimic epitopes of MgPa.And S,A,F K,I,T,L,R and D may be the key amino acid residues for the epitopes of MgPa.

Objective To investigate therapeutic mechanism of radiation therapy associated with Doeetaxel on human uterine cervi-cal carcinoma. Method Hela cells were incubated with 0. 5 μmol/L, 1.01 μmol/Docetaxel for 24 hours, and were radiated with 0, 2, 4, 6, 8Gy X ray. The proliferation activity was detected with MTT method. Apoptosis was evaluated with TUNEL method. Expression of caspase-3 protein and the degradation fragment was measured with Western blot. Result Inhibitory effect of radiation therapy associated Docetaxel on Hela cells was significantly stronger than that of radiation group. Treated with 2 Gy and 6MV X ray radiation, inhibitory rate of Hela cells increased with the increment of associated Docetaxel doses (P<0.05). Inhibitory rate of Hela cells in radiation associated Docetaxel group was significantly increased compared with radiation group. Apoptosis index in radiation associated Docetaxel group 48 hours after treatment was significantly increased compared with radiation group or Docetaxel group with TUNEL method (P<0.05). Western blot results indies-ted that caspase-3 protein was degraded and small active fragments were produced. Conclusion The reason that Docetaxel enhanced Hela cell radiation sensitivity may probably he correlated to easpase-3 protein activation.

Objective To explore the recuperative effect of immunological function and nutritional status on the patients treated by immune enteral nutrition in early stage after severe multiple injury (SMI). Method The patients with SMI,in department of Trauma Surgery,Tongji Hospital,Tongji Medical College, Huazhong University of Science and Technology,between January 2006 to May 2007 were randomly divided into 2 groups: immune enteral nutrition group (IEN group, 20 cases), enteral nutrition group (EN group, 20 cases). The health persons served as the control group(15 cases) .Since 1st postinjury day, all patients were treated with nutritional support. The T-cell subgroup in periphera blood were detected by FCM and the level of PA, RBP, IL-2 and IL-4 in blood serum were detected by ELASA on the 1st, 3rd,5th, 8th postinjury day. Results After the treatment of IEN and EN,the serum levels of PA, RBP and the proportion of T-cell subgroup were significantly increased on the 8th postinjury day compared with on 1st postinjury day (P ＜ 0.01), but there were no differences between IEN group and EN group. The level of IL-4 were significantly decreased and the level of IL-2 were significantly increased in each group on 8th postinjury day, at same time, the level of IL-2 were significantly increased in IEN group compared with EN group (P ＜ 0.05), and the level of IL-4 were significantly decreased in IEN group compared with EN group (P ＜ 0.05). The duration of SIRS was transient and the infected complication was low on the patients treatment by IEN than EN. Conclusions On the patients with severe multiple injury, IEN was most ascendant than EN to improve the immunosuppression and clinical prognosis.

Objective To stuay the serum levels of sCD40L,hsCRP,ICAM-1 and VCAM-1,and the expression of CD40L of the CD4+T cells in patients withacute coronary syndrome(ACS),and to explore the relationship between CD40L and inflammatory factors and the effects of CD40/CD40L on ACS.Method Thirty-two coronary heart disease patients without history of other discernible systemic disease and medicine of steroids or immunosuppressants taken were divided into acute myocardial infarction group(AMI,n=11),unstable angina pectoris group(USP,n=14)and stable angina pectoris group(SAP,n=7).The control group was composed of eight healthy volunteers(CON group).Theexpression of CD40L Was determined by flow cytometry(FCM).Serum sCD40L.ICAM-1 and VCAM-1 were determined by using ELISA.The serum hsCRP was assayed by using immunoturbidimetry.Data were analyzed with SPSS 11.0 software for windows.Results The expression percentage(%)of CD40L of the CD4+T cells,and the serum levels of sCD40L,hsCRP,ICAM-1 and VCAM-1were sifnificantly higher in patients of AMI group than those in patients of other groups(P＜0.05 or P＜0.01).Similarly,those biomarkers in patients of UAP group were usually higher than those in patients of CON or SAP groups(P＜0.05).There Was a positive correlation between the expression of CD40L and the serum level of VCAM-1 in paients of AMI group(P＜0.05),and likewise,a positive correlation also existed between the serum level of sCD40L and other factors,hsCRP,ICAM-1 as well as VCAM-1,in patients of AMI group(P＜0.05).Conclusions The enhanced expression of CD40L of the CD4+T cells and high serum level of sCD40L are present in patients with acute coronary syndrome.The hsCRP,ICAM-1 and VCAM-1 play roles in the pathogenesis of ACS,and they have correlation with enhanced expression of CD40L and high serum level of sCD40L.Therefore,CD40L and sCD40L may be used as indicators of risk in coronary heart disease.

[Objective]To evaluate the results of arthroscopic capsular release for the treatment of idiopathic frozen shoulder.[Method]From January 2004 to April 2005,7 patients with diagnosis of idiopathic frozea shoulder,who had symptoms for an average of 8.0 months(5 to 13months)with failed conservative treatment for at least 4 months,were treated with arthroscopic capsular release combined with rehabilitaticon exercises after operation.Under general anesthesia,all the patients underwent arthroscopic capsular release and manipulation.All patients were strictly evaluated by Constant score,normalized Constant score and the Visual Analog Scale(VAS 1 to 15 points,1 = no pain),before operation,at 3 weeks after operation,3 months after operation and 17.2 months after operation respectively.[Result]All patients were followed up with a mean of 17.2 months(8 to 23 months).The average in-hospital day was 8.1 days(7 to 10 days).All patients had significant improvement in terms of functional gain and pain relief after operntion.The preoperative pain score improved from(5.2?2.4)points to(11.2?2.0),(14.6?0.4)and(14.7?0.4)points at 3 weeks after operation,3 months after operation end 17.2 months after operation respectively.The Constant score improved from(24.5?14.2)to(47.0?18.8),(68.9?9.4)and(70.1?7.9),and the normalized Constant score improvad from(31.0%?17.3%)to(60.1%?24.9%),(87.1%?14.5%)and(89.7%?12.1%).There was no complication in the treatment procedures.[Conclusion]Arthrosenpic capsular release is a safe and effective surgical procedure in the management of idiopathic frozen shoulder unresponsive to conservative treatment.It has advantages of little invasive,better recovery,less operation time and less complications.