AIM:To observed the protective effect of diminazene aceturate(DIZE),an angiotensin-converting enzyme 2(ACE2)activator,on rats with diabetic cardiomyopathy(DCM).METHODS:Male Wistar rats(n=30)were randomly divided into normal control group ,DCM group and DIZE treatment group(DIZE group).The rats in DCM group and DIZE group were intraperitoneally injected with streptozotocin(65 mg/kg )to establish diabetic model.After 12 weeks,the diabetic rats were infused with DIZE at 15 mg· kg-1 · d-1 or the same volume of saline for 4 weeks using os-motic minipump.The cardiac function was measured at the end of the 16th week.The methods of Mason staining and HE staining were used to observe the morphological changes of the myocardial tissue.Western blot ,ELISA and immunohisto-chemistry were used to observe the changes of ACE2,angiotensin(Ang)Ⅱ,Ang-(1-7),interleukin(IL)-1,IL-6 and connective tissue growth factor(CTGF).RESULTS:DIZE significantly improved the expression of ACE 2 in diabetic rats(P<0.05).Compared with DCM group,the levels of IL-1 and IL-6 in DIZE group were significantly decreased ,and the cardiac function in DIZE group was significantly improved(P<0.05).CONCLUSION:ACE2 endogenous agonist DIZE significantly increases the ACE 2 level and reduces the level of inflammation ,thus protecting the heart function of DCM rats.

OBJECTIVETo identify factors associated with YMDD mutation in patients with chronic hepatitis B before and after lamivudine treatment in Zunyi region.

METHODS53 patients with chronic hepatitis B were enrolled in this study, HBV DNA,HBV markers, ALT, AST, TBil, albumin in the serum were examined at 0, 3, 6, 12, 18 and 24 months after lamivudine treatment. HBV genotype and YMDD mutation were determined by sequencing before lamivudine treatment. YMDD mutation was checked again if serum HBV DNA rebound to more than 1 x 10(4) copies/ml after the initial decrease.

RESULTSHBV genotype in Zunyi region is constitute of B, C and B+C genotype. YMDD mutation occurred in 18 cases after lamivudine treatment, the rate of YMDD mutation was 15.1%, and 34.0% after 1 year and 2 years treatment. There are four types of mutation: rtL180M/M204V, rtL180M/M204I, rtM204I, rtL180M. rtM204V mutation in C gene was always accompanied by rtL180M mutation (100%). The rate of rtL180M/M204V mutation in genotype C group was significantly higher than that in genotype B group (77.8% to 25.0%), the same was true for the rtL180M/ M204I mutation (22.2% to 12.5%). There was no point mutation in genotype C group. The point mutation of rtM204I and rtL180M appeared only in genotype B group. Gender, nation, family history of hepatitis B and HBeAg were not associated with YMDD mutation (P more than 0.05), while the mutation rate was associated with the disease course and severity of disease. YMDD mutation did not occur in patients with low HBV DNA level (less than 10(5) copies/ml).

CONCLUSIONYMDD mutation after lamivudine therapy is associated with HBV genotype and P gene mutation type, and prolonged treatment increases the the mutation rate. In order to reduce the incidence of YMDD mutation, patients with shorter disease course, lower HBV DNA level, more serious liver damage should be treated with lamivudine.

Adult ; Alanine Transaminase ; blood ; Antiviral Agents ; pharmacology ; therapeutic use ; Aspartate Aminotransferases ; blood ; China ; epidemiology ; DNA Mutational Analysis ; DNA Primers ; DNA, Viral ; blood ; genetics ; Drug Resistance, Viral ; Female ; Genotype ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Lamivudine ; pharmacology ; therapeutic use ; Male ; Mutation ; Polymerase Chain Reaction

Objective: To investigate the application of high-frequency ultrasound in dermabrasion of patients with deep partial-thickness burns. Methods: Twenty-six patients with deep partial-thickness burns conforming to the study criteria were hospitalized in our unit from March 2015 to March 2016. Patients were all performed with dermabrasion. The structure of skin tissue and blood flow signals of uninjured side and wounds before dermabrasion, and those of wounds immediately post dermabrasion and on post dermabrasion day (PDD) 1, 3, 5, 7, 10, 14, and 21 were detected with high-frequency ultrasound, and the percentage of blood flow signals was calculated. According to the results of comparison between percentage of blood flow signals of wounds and that of normal skin before dermabrasion, patients were divided into no significant decrease group (NSD, n=19) and significant decrease group (SD, n=7). Wound healing time of patients in two groups was recorded. Data were processed with analysis of variance of repeated measurement, LSD test, t test and Chi-square test. The correlation between the percentage of blood flow signals of wounds before dermabrasion and wound healing time of 26 patients were analyzed by Spearman correlation analysis. Results: (1) Epidermis of normal skin of patients in two groups before dermabrasion showed continuous smooth linear hyperecho, which was stronger than that of dermis, and boundary of dermis and subcutaneous tissue showed stronger discontinuous linear echo than that of dermis, which gradually transited to subcutaneous tissue. In group NSD, epidermis of wound of patients before dermabrasion showed intermittent rough linear echo, which was weaker than that of normal skin epidermis, and there was no obvious abnormity of boundary between dermis and subcutaneous tissue. Immediately post dermabrasion and on PDD 1, no linear hyperecho of epidermis was observed, showing complete attrition of epidermis, and the echo of dermis and subcutaneous tissue had no obvious change as compared with that before dermabrasion, with flat surface of dermis and partly abraded superficial-dermis but relatively well preserved dermal tissue in whole. The epidermis showed discontinuous linear hyperecho, and epidermis was discontinuously regenerated on PDD 3 and 5. Partial continuous linear hyperecho was detected in the epidermis, showing partial continuous regeneration of epidermis on PDD 7 and 10. The regenerated epidermis was thicker than normal skin epidermis and showed rough linear hyperecho with non-uniform thickness on PDD 14. The regenerated epidermis was thicker than normal skin epidermis and showed rather smooth linear hyperecho with uniform thickness on PDD 21. In group SD, the structure of epidermis and dermis of wound of patients before dermabrasion, immediately post dermabrasion, and on PDD 1 was similar to that in group NSD, but the echo of boundary of dermis and subcutaneous tissue was weakened in different degrees. There was no linear hyperecho of epidermis, showing no epidermis was regenerated on PDD 3 and 5. Intermittent regeneration of epidermis appeared on PDD 7 and 10 with intermittent linear hyperecho. Partial continuous linear hyperecho was detected in the epidermis, showing partial continuous regeneration of epidermis on PDD 14 and 21. (2) The percentages of blood flow signals of wounds of patients in group NSD before dermabrasion, immediately post dermabrasion, and on PDD 1 were (3.1±1.3)%, (6.5±2.0)%, and (5.3±1.9)% respectively, higher than those in group SD [(0.9±1.1)%, (3.5±1.3)%, and (3.6±0.9)% respectively, P<0.05 or P<0.01]. The percentages of blood flow signals of wounds of patients in two groups were similar at the other time points (with P values above 0.05). Compared with the percentage of normal skin in the same group [(3.2±0.7)%], the percentages of blood flow signals of wounds of patients in group NSD were significantly increased immediately post dermabrasion and on PDD 1 (with P values below 0.01) but had no significant change at the other time points (with P values above 0.05). The percentage of blood flow signals of wounds of patients before dermabrasion in group SD was significantly lower than that of normal skin in the same group [(2.8±0.6)%, P<0.01]. The percentage of blood flow signals of wounds of patients in group SD was close to that of normal skin in the same group at each time point post dermabrasion (with P values above 0.05). (3) The wound healing time of patients in group NSD was (16.2±2.5) d, lower than that in group SD [(30.9±2.9) d, t=12.67, P<0.01]. There was obvious negative correlation between the percentage of blood flow signals of wounds before dermabrasion and wound healing time of 26 patients (r=-0.77, P<0.01). Conclusions High-frequency ultrasound is a good way to observe the imaging features of wounds in patients with deep partial-thickness burns before and after dermabrasion, and it can provide objective imaging evidence for the performance of dermabrasion in patients with deep partial-thickness burns.

BACKGROUNDThe ultimate goal of hepatitis B treatment is hepatitis B surface antigen (HBsAg) seroclearance. Several factors have been suggested to be associated with the rate of HBsAg reduction in antiviral-naive or lamivudine therapy cohorts. However, there are few studies evaluating the factors during long-term entecavir (ETV) therapy. In the present study, we aimed to evaluate the factors to predict the outcome of ETV therapy for 7 years.

METHODSA total of 47 chronic hepatitis B (CHB) patients treated with ETV monotherapy were included in this study. Liver biochemistry, hepatitis B virus (HBV) serological markers, serum HBV DNA, and HBsAg titers were tested at baseline, 3 months, 6 months, and yearly from 1 to 7. The associations between factors and HBsAg reduction were assessed using multivariate tests with repeated measure analysis of variance.

RESULTSAt baseline, serum HBsAg levels showed a positive correlation with baseline HBV DNA levels (r = 0.625, P < 0.001). The mean HBsAg titers after ETV treatment were significantly lower than the baseline titers (P ranges from 0.025 to 0.000,000,6). The HBsAg reduction rate during the 1st year was greater compared to after 1 year of treatment (P < 0.05). Multivariate test showed that hepatitis B e antigen (HBeAg) seroclearance and/or HBsAg reduction ≥0.5 log10 IU/ml at 6 months had a high negative predictive value (96.77%) for HBsAg seroclearance (P = 0.002, P = 0.012, respectively).

CONCLUSIONSThe HBsAg reduction rate during the 1st year was greater than that after 1 year of treatment. Further, HBeAg status and HBsAg levels at month 6 are the optimal factors for the early prediction of HBsAg seroclearance after long-term ETV therapy in CHB patients.

Adult ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Female ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Male ; Middle Aged

OBJECTIVETo investigate the quantities of monocyte-derived dendritic cell precursors (pDC1) and plasmacytoid dendritic cell precursors (pDC2) in peripheral blood mononuclear cells (PBMC) of severe aplastic anemia (SAA) patients before and after immune suppressive therapy (IST), the ratio of the pDC1 to pDC2, and the expression of co-stimulating molecules (CD80, CD86, CD40) on dendritic cells (DC) and B cells in SAA patients.

METHODSBy means of three color monoclonal antibody labeling technology, the quantities and ratio of pDC1 and pDC2 in PBMC were detected in 26 SAA patients at active phase, 13 at recovery phase and 15 normal controls respectively. The aforementioned parameters of 10 SAA patients were tested before and 2 months after IST. The expression of CD80, CD86 and CD40 on DC and B lymphocytes were detected in 16 SAA patients and 15 normal controls.

RESULTSThe percentages of pDC1 and the ratio of pDC1/pDC2 of controls were (0.41 +/- 0.05)% and 1.58 +/- 0.18 respectively, and those of SAA patients at active phase were (0.67 +/- 0.13)% and 2.70 +/- 0.32 respectively, [pDC1 (P < 0.05); pDC1/ pDC2 ratio (P < 0.01)]. The aforementioned parameters in convalescent SAA patients decreased to (0.43 +/- 0.10)%, and 1.78 +/- 0.36 respectively, being no difference from those of normal controls. The percentages of pDC1 and pDC2 in 10 SAA patients were (0.87 +/- 0.31)%, and (0.35 +/- 0.09)%, before IST, and (0.24 +/- 0.09)%, (0.14 +/- 0.04)%, after IST, being significantly decreased (P < 0.05). The percentages of CD86 expression on DC of controls was (11.97 +/- 4.31)%, and that of SAA patients was (29.84 +/- 3.02) % (P < 0.05). The percentages of CD80, CD40 and CD86 expression on lymphocytes of controls were (2.57 +/- 0.44)%, (7.34 +/- 1.22)% and (1.86 +/- 1.11)%, respectively, and those of SAA patients were (5.17 +/- 0.68)%, (8.85 +/- 2.94)% and (5.98 +/- 0.96)% respectively (P < 0.05, P < 0.01). The percentage of CD86 expression on B lymphocytes in controls was 8.04 +/- 0.66%, and in SAA patients was (20.46 +/- 2.78)%, (P < 0.05).

CONCLUSIONThe pDC subtypes were abnormal and the percentage of pDC1 is increased in SAA patients, which are associated with stage of this disease. DC and B Lymphocytes in SAA patients upregulated expression of costimulatory molecules (CD86) which cause the T lymphocyte abnormally activated.

Adolescent ; Adult ; Anemia, Aplastic ; immunology ; B-Lymphocytes ; immunology ; metabolism ; B7-1 Antigen ; blood ; B7-2 Antigen ; blood ; CD40 Antigens ; blood ; Case-Control Studies ; Child ; Convalescence ; Dendritic Cells ; immunology ; metabolism ; Female ; Flow Cytometry ; Humans ; Male ; Middle Aged

Objective To evaluate the efficacy of quadrates lumborum block for unilateral inguinal hernia repair in elderly patients. Methods Fifty-eight elderly patients with unilateral inguinal hernia of both sexes, aged 65-80 yr, with body mass index of 18-25 kg∕m2 , of American Society of Anesthesiolo-gists physical status Ⅱ or Ⅲ, scheduled for elective unilateral tension-free repair, were divided into 2 groups ( n=29 each) using a random number table method: iliohypogastric-ilioinguinal nerve block group (group T) and quadrates lumborum block group (group Q). Iliohypogastric-ilioinguinal nerve block with arteria circumflexa ilium profunda as a marker was carried out with 0. 33％ ropivacaine 20 ml under ultra-sound guidance in group T. The anterior approach to quadratus lumborum block was performed with 0. 33％ropivacaine 20 ml under ultrasound guidance in group Q. Operation was started after the height of sensory block was assessed by pin-prick test at 30 min after block. When the blocking effect did not meet the opera-tion requirements, an increment of 1％ lidocaine 2. 5 ml was given every time in the surgical field until op-eration requirements were met. Dexmedetomidine was intravenously infused at a rate of 0. 03-0. 07μg·kg-1 ·min-1 during surgery until the end of surgery to maintain Narcotrend index between 80 and 90. When postoperative visual analogue scale score >3, parecoxib sodium 40 mg was intravenously injected, and if marked pain relief was not found 10 min later, tramadol hydrochloride 50-100 mg was intravenously injected. The upper spread of sensory block and intraoperative requirement for additional local anesthetics were recorded at 30 min after nerve block. The requirement for parecoxib and tramadol was recorded within 48 h after operation. The development of inadvertent intravascular injection of local anesthetics, local anes-thetic intoxication and postoperative nausea and vomiting, nerve block of lower extremity and uroschesis was recorded. Results Skin pain disappeared at the plane of T11-L1 in group T and at the plane of T9-L1 in group Q. Compared with group T, the intraoperative requirement for and consumption of local anesthetics, postoperative requirement for parecoxib and tramadol, and postoperative incidence of nausea and vomiting were significantly decreased in group Q ( P<0. 05) . Conclusion Quadrates lumborum block provides bet-ter efficacy for unilateral inguinal hernia repair than iliohypogastric-ilioinguinal nerve block in elderly pa-tients.

Objective:To observe the effect of combining biofeedback therapy (BFT) based on virtual reality technology with repeated transcranial magnetic stimulation (rTMS) on dysphagia among stroke survivors.Methods:Eighty patients were randomly divided into a control group, an rTMS group, a BFT group and a combined treatment group, each of 20. In addition to routine dysphagia rehabilitation, the rTMS and BFT groups were given those treatments, while the combined treatment group was given both for 4 weeks. Swallowing function was evaluated before and after the treatment using the standardized swallowing assessment (SSA) and the functional oral intake scale (FOIS). Videofluoroscopy was used to quantify the subjects′ oral and pharyngeal phases and their aspiration status.Results:Significant improvement was observed in the average FOIS and SSA scores, as well as in the average oral and pharyngeal phases and in aspiration. The combined treatment group′s results were significantly better in all those aspects than those of the other 3 groups.Conclusion:The combined application of biofeedback therapy based on virtual reality technology and repeated transcranial magnetic stimulation can improve the swallowing function of stroke survivors with dysphagia. It is worthy of clinical promotion.

Objective To construct c-Met CAR-T cells secreting PD-1 antibodies to reduce immune inhibitory effect of tumor cells and enhance the efficacy of CAR-T cell therapy against pancreatic cancer.Methods Kaplan-Meier Plotter,GEPIA,and Timer 2.0 bioinformatics databases were used to analyze c-Met expression in pancreatic cancer and its correlation with survival and immune infiltration status.In clinical samples of pancreatic cancer and pancreatic cancer Aspc-1 cells,c-Met and PD-L1 expressions were detected using immunohistochemistry or flow cytometry.Using gene editing technology,PD-1 secretory antibodies and HIS tags were linked to second-generation c-Met CAR molecules to construct PD-1/c-Met CAR plasmids,which were then packaged into lentiviruses for infection of activated T cells.The positive rate and cell subset distribution of CAR-T cells were analyzed with flow cytometry,and secretory PD-1 antibodies in cell supernatants were detected using Western blotting.The target cell killing efficiency and proliferative activity of the modified CAR-T cells were evaluated after activation,and cytokine secretion was analyzed using ELISA.Results The expression of c-Met was significantly higher in pancreatic cancer than in normal tissues,and its expression level was negatively correlated with the patients'survival and positively correlated with immune cell infiltration.The clinical samples of pancreatic cancer tissues expressed significantly higher levels of c-Met and PD-L1 than the adjacent tissues,and 90.7%and 57.7%of Aspc-1 cells were positive for c-Met and PD-L1,respectively.The constructed PD-1/c-Met CAR-T cells were capable of secreting PD-1 antibodies and showed a significantly higher killing efficiency against tumor cells than c-Met CAR-T cells at an effector-to-target ratio of 20:1,with also a higher proliferative activity after target cell stimulation and higher levels of IL-2 and TNF-α secretin.Conclusion PD-1/c-Met CAR-T cells have higher killing efficiency against pancreatic cancer cells with also higher proliferative activity than c-Met CAR-T cells.

Objective To construct c-Met CAR-T cells secreting PD-1 antibodies to reduce immune inhibitory effect of tumor cells and enhance the efficacy of CAR-T cell therapy against pancreatic cancer.Methods Kaplan-Meier Plotter,GEPIA,and Timer 2.0 bioinformatics databases were used to analyze c-Met expression in pancreatic cancer and its correlation with survival and immune infiltration status.In clinical samples of pancreatic cancer and pancreatic cancer Aspc-1 cells,c-Met and PD-L1 expressions were detected using immunohistochemistry or flow cytometry.Using gene editing technology,PD-1 secretory antibodies and HIS tags were linked to second-generation c-Met CAR molecules to construct PD-1/c-Met CAR plasmids,which were then packaged into lentiviruses for infection of activated T cells.The positive rate and cell subset distribution of CAR-T cells were analyzed with flow cytometry,and secretory PD-1 antibodies in cell supernatants were detected using Western blotting.The target cell killing efficiency and proliferative activity of the modified CAR-T cells were evaluated after activation,and cytokine secretion was analyzed using ELISA.Results The expression of c-Met was significantly higher in pancreatic cancer than in normal tissues,and its expression level was negatively correlated with the patients'survival and positively correlated with immune cell infiltration.The clinical samples of pancreatic cancer tissues expressed significantly higher levels of c-Met and PD-L1 than the adjacent tissues,and 90.7%and 57.7%of Aspc-1 cells were positive for c-Met and PD-L1,respectively.The constructed PD-1/c-Met CAR-T cells were capable of secreting PD-1 antibodies and showed a significantly higher killing efficiency against tumor cells than c-Met CAR-T cells at an effector-to-target ratio of 20:1,with also a higher proliferative activity after target cell stimulation and higher levels of IL-2 and TNF-α secretin.Conclusion PD-1/c-Met CAR-T cells have higher killing efficiency against pancreatic cancer cells with also higher proliferative activity than c-Met CAR-T cells.

Objective: To explore the persistent viral response rate (SVR) in patients with refractory chronic hepatitis C after interferon (IFN) (peginterferon 360 μg qw) and ribavirin (PR) therapy failure. The SVR of patients with refractory chronic hepatitis C was improved by PR combined with direct antiviral agents (DAA) and proper extension of the course of therapy was applied. Methods: Seventeen cases of refractory chronic hepatitis C after IFN(peginterferon 360 μg qw) and ribavirin therapy failure were given PR combined with DAA treatment. The side effects were observed and corresponding adjustments were made on drug dosage, and SVR was recorded. Results: The 17 cases completed the whole course of treatment with PR combined with DAA for 24 weeks. All the 17 patients obtained rapid viralogical response (RVR) and SVR. After treatment, the SVR rate was 100% in patients including those with virologic relapse, retreated or previously non-responsive patients with refractory chronic hepatitis C. The adverse reaction of PR combined with DAA 24 weeks was generally mild. Conclusions The use of PR combined with DAA re-treatment in patients with refractory chronic hepatitis C can achieve SVR and shorten the treatment time. PR combined with DAA re-therapy is one of effective treatments to improve the rate of sustained viral response in patients with refractory chronic hepatitis C.