Background Hypertension is a multigenetic inheritable disease.Gene therapy with long-term effects and less side effects by regulating gene expression has been shown to be a potential and exciting prospect. Objective To investigate the effects of RNA interference(RNAi)targeting angiotensin-converting enzyme(ACE)on the blood pressure and ACE expression in kidney of spontaneously hypertensive rats(SHR).Methods SHR were randomly to receive placebo(n=12)or control adenovirus Ad5-EGFP)or a single injection of recombinant adenovi- ral vectors,Ad5-EGFP-ACE-shRNA(n=12,iv).Normotensive Wistar-Kyoto rats(WKY)were served as normal control group.SBP was measured before and after the intervention.Aorta,lung,myocardium and kidney were studied using fluorescence microscope to identify the sites of Ad5-EGFP-ACE-shRNA.Expressions of ACE mRNA and protein in kidney were evaluated by RT-PCR and Western blot.Results SBP of the treat group was effectively reduced by 19.0?3.2 mmHg at the 3rd day,and 22.1?3.3 mmHg at the 13th day of the experiment.The anti- hypertensive effect significant remained at least for 14 days.On the contrary,increase in BP was shown in placebo and the adenovirus control group.Compared with placebo or adenovirus control rats,ACE mRNA expression level in kidney of the treated rats was lower by 61.1% and 62.3% respectively,with ACE protein expression level lower- ing by 56.2% and 53.30% as well(ail P0.05). Conclusion RNA interference targeting ACE gene inhibits the expressions of ACE mRNA and protein.A single dose injection resulted in a prolonged decrease in BP.The evidence of strong antihypertensive effect by genetic therapy justifies efforts for further investigation.

OBJECTIVETo evaluate a retro-grade auricular flap for repairing large alar defects.

METHODSTwenty-nine adult cadavers were anatomically used for vascular investigation of the frontal, nasal and temporal regions by injecting a dye into the main vessels. Based on the anatomical study in these regions, a retro-grade auricular flap was designed for repairing alar defects in 16 patients.

RESULTSThe blood supply of the auricle could be nourished by the inner carotid artery system from the supratrachlear artery and supraorbital artery through the frontal arterial anastomotical network into the frontal branch of the superficial temporal artery. It is then passing the main trunk of the superficial temporal artery into the ear area through the auricular branches of the superficial temporal artery. The retro-grade auricular island flap could be formed by basing the supratrachlear artery and the supraorbital artery through the vascular network between the superficial temporal artery and the supratrachlear artery or the supraorbital artery. Sixteen patients with large alar defects and half-sized nasal defects were successfully repaired by this technique.

CONCLUSIONSThe retro-grade auricular island flap, based on the inner carotid artery system, could be a good and safe flap for repairing a large alar defect or half-sized nasal reconstruction.

Adult ; Arteries ; Cadaver ; Carotid Artery, Internal ; Ear Auricle ; blood supply ; Humans ; Nose Deformities, Acquired ; surgery ; Ophthalmic Artery ; Reconstructive Surgical Procedures ; Surgical Flaps ; blood supply ; transplantation ; Temporal Arteries

OBJECTIVETo investigate the effect of cerebral state index (CSI) in measuring the level of sedation during target controlled infusion (TCI) of propofol in patients of different ages.

METHODSForty ASA class I-II patients undergoing general anesthesia were divided into group A (65 to 79 years old, n=20) and group B (20 to 55 years, n=20). The sedation level was assessed using OAA/S scale. Anesthesia was induced with TCI of propofol. The target effect-site concentration (CE) was set initially at 0.5 µg/ml followed by increments of 0.5 µg/ml every 5 min until 5 min after the patients lost consciousness and did not respond to pain stimulation (OAA/S=0). OAA/S score was recorded every 20 s, and MAP, HR, SPO(2) and CSI were recorded. Spearman correlation coefficient between OAA/S score and CSI and their prediction probabilities (Pk) were calculated. The values of CE(05), CE(50), CE(95) and CSI(05), CSI(50), CSI(95) at loss of verbal contact (LVC) (OAA/S=2) and loss of consciousness (LOC) (OAA/s≤1) were also calculated.

RESULTSCSI was well correlated to the sedation depth. The values of CE(50) and CSI50 were 1.3 µg/ml and 69.7 at LVC in group A, and were 1.8 µg/ml and 65.9 at LVC in group B, respectively. The values of CE(50) and CSI(50) were 1.5 µg/ml and 64.3 at LOC in group A, as compared to 2.5 µg/ml and 54.8 at LOC in group B, respectively. When the OAA/S scale was lower than 3, the CSI values in group A were significantly higher than those in group B (P<0.05).

CONCLUSIONCSI can effectively and rapidly distinguish the level of sedation in different age groups. At the same OAA/S scale, the target effect-site concentration in the elderly is obviously lower than that in the young patients, but CSI values were significantly higher in the elderly than in the young patients during TCI of propofol.

Adult ; Aged ; Consciousness ; Deep Sedation ; Electroencephalography ; Female ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Monitoring, Intraoperative ; Propofol ; administration & dosage ; Young Adult

OBJECTIVE: To determine an optimal clinical dose of ketamine after comparing the efficacy and security of 3 low dose ketamines mixed with butorphanol in the postoperative continuous intravenous analgesia. METHODS: Eighty ASA (American Society of Anesthesiologists) I-II patients scheduled for elective gynecological surgery under general anesthesia were divided randomly into 4 groups (n=20): Group B received butorphanol 3 microg/(kg x h);Group BK1 received butorphanol 2 microg/(kg x h) mixed with ketamine 60 microg/(kg x h); Group BK2 received butorphanol 2 microg/(kg x h) mixed with ketamine 90 microg/(kg.h); and Group BK3 received butorphanol 2 microg/(kg x h) mixed with ketamine 120 microg/(kg x h). Continuous intravenous infusion pump was used when the patients had obvious pain (visual analgesia scale of five), and the bolus infusion (4 mL) was given before the operation, and continuous infusion at 2 mL/h. In the postoperative period, pain was assessed using visual analogue scale (VAS) at 2,6,12,24, and 48 h.At the same time, Ramsay scores and adverse effects were recorded. RESULTS: There was no significant difference in the adverse effects and the postoperative mean arterial pressure, heart rate, respiratory rate values, and pulse oxygen among the 4 groups. Postoperative VAS values in Group BK3 was the lowest, followed by Group BK2. There was no significant difference between Group BK1 and Group B. The incidence of somnolence in Group B was higher than that in Group BK1, BK2 and BK3(P<0.05). CONCLUSION Ketamine in subanaesthetic dose added to butorphanol for postoperative continuous intravenous infusion has a better postoperative analgesic effect and sedation. It can effectively spare butorphanol consumption without increasing adverse effects. The optimal combined dose is 90-120 microg/(kg x h).
Adult ; Analgesia ; methods ; Analgesics ; administration & dosage ; Butorphanol ; administration & dosage ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Gynecologic Surgical Procedures ; Humans ; Infusions, Intravenous ; Ketamine ; administration & dosage ; Pain, Postoperative ; drug therapy

Objective To investigate the effects of RNA interference(RNAi)targeting angiotensinconverting enzynle(ACE)on the blood pressure and myocardial remodeling in spontaneously hypertensive rats(SHRs).Methods Saline(control),adenovirus(Ad5)and recombinant adenoviral vectors(Ad5-ACE-shRNA expressing ACE gene-specific shRN)were randomly administered by caudal intravenation to SHRs(n=12 each group)at day 1 and day 16.Normotensive Wistar-Kyoto rats(WKY)served as normal controls.Systolic blood pressure(SBP)of the caudal artery was measured daily.Expressions of ACE at mRNA and protein levels in myocardium and aorta were evaluated by RT-PCR and Western blot respectively,ACE serum concentration was measured by ELISA at day 3(n=6 each group).The ratio of left ventricular to body weight(LVW/BW),myocardial collagen content were measured and myocardial uhrastrueture observed under transmission electron microscope at the study end.Results Ad5-ACE-shRNA injection significantly reduced SBP(-22 mm Hg,1 mm Hg=0.133 kPa)and the antihypertensive effect could last at least 14 davs post each injection.SBP was not affected by saline and Ad5 injections.ACE expressions at mRNA and Drotein levels at myocardium and aorta as well as serum ACE were significantly decreased in Ad5-ACE-shRNA treated SHRs compared to that in saline and Ad5 groups(all P＜0.05)and was coinparable to that in WKY group(P＞0.05).The LVW/BW ratio(2.24±0.19)and myocardial collagen content[(1.283±0.019)μg/mg]in Ad5-ACE-shRNA treated SHRs were also significantly lower than those in saline treated[3.21±0.13 and (1.686±0.013)μg/mg,both P＜0.05]and Ad5 treated SHRs [3.13 ±0.12,(1.682±0.009)μg/mg,both P＜0.05]but still higher than those of WKY group[2.06±0.11,(1.257±0.019)μg/mg,both P＜0.05].Myocardial uhrastructure was also significantly improved in Ad5-ACE-shRNA treated SHRs compared to saline and Ad5 treated SHRs.Conclusion RNAi targeting ACE gene significantly inhibited the expressions of ACE at mRNA and protein levels and resuhed in prolonged antihypertensive effects and myocardial uhrastructure improvements in this SHR model.

Objective To investigate the effects of RNA interference (RNAi) targeting angiotensin Ⅱ Type 1 receptor (AT1R) and angiotensin-converting enzyme (ACE) on blood pressure and myocardial remodeling in spontaneous hypertensive rats (SHRs). Methods Saline (control), adenovims (Ad5) and recombinant adenoviral vectors (Ad5-ACE-shRNA, Ad5-AT1R-shRNA and Ad5-ACE-AT1R-shRNA expressing ACE, AT1R, ACE and AT1R gene-specific shRNA, respectively) were randomly administered by caudal intravenation to SHBs (n = 12 each group) at day 1 and 17. Normotensive Wistar-Kyoto rats (WKY) served as normal controls. Systolic blood pressure (SBP) of the caudal artery was measured daily. Expression of ACE and AT1R at mBNA levels in ventricle and aorta were evaluated by fluorescence quantitative PCR. Angiotension Ⅱ serum concentration was measured by ELISA at day 3 (n = 6 each group). The ratio of left ventricular to body weight (LVW/BW) and myocardial collagen content were measured, myocardial ultrastructure observed under transmission electron microscope at the study end. Results The caudal artery pressure of saline and Ad5 group was equally increased by about 26 nun Hg(1 mm Hg=0.133 kPa) compared to baseline (both P <0.05). Ad5-ACE-shRNA,Ad5-AT1R-shRNA and Ad5-ACE-AT1R-shRNA injection significantly reduced SBP (-24 mm Hg, -22 mm Hg and -26 mm Hg respectively, all P<0.05 vs. baseline) and the antihypertensive effect could last at least 15 days post each injection. SBP was not affected by saline and Ads injections. ACE and AT1 mRNA expressions at ventricle and aorta were significantly decreased in Ad5-ACE-shRNA, Ad5-ACE-AT1R-shRNA and Ad5-AT1R-shRNA, Ad5-ACE-AT1R-shRNA treated SHRs compared to those in saline and Ad5 groups (all P < 0.05) and was comparable to that in WKY group (P> 0.05). The LVW/BW ratio [(2.22±0.18)μg/mg, (2.23 ±0.19)μg/mg, (2.17±0.16) μg/mg] and myocardial collagen content [(1.291±0.019)μg/mg, (1.298±0.019) μg/mg, (1.276±0.019)μg/mg] in Ad5-ACE-shRNA, Ad5-AT1R-shRNA and Ad5-ACE-AT1R-shRNA treated SHBs were also significantly lower than those in saline treated [(3.23±0.13) μg/mg and(1.683±0.013) μg/mg, both P<0.05] and Ad5 treated SHRs [(3.25±0.12) μg/mg and (1.693±0.013) μg/mg, both P<0.05], but still higher than those of WKY group [(2.06±0.12) μg/mg and (1.258±0.019) μg/mg, both P < 0.05]. Myocardial ultrastructure was also significantly improved in all SHRs underwent RNAi treatments compared to saline and Ad5 treated SHRs. Conclusion RNAi targeting ACE and AT1R gene significantly inhibited myocardial and aortic ACE and AT1R mRNA expressions and resulted in prolonged antihypertensive effects and myocardial ultrastructure improvements in SHRsl. The RNAi technology may be a potential new strategy of gene therapy for hypertension.

Objective:To explore effect of dapagliflozin on oxidative stress and left ventricular hypertrophy in patients with type 2 diabetes mellitus(T2DM)and chronic heart failure(CHF).Methods:A total of 114 T2DM+CHF pa-tients treated in our hospital from January 2020 to October 2020 were included.They were divided into routine group(traditional medication)and dapagliflozin group(dapagliflozin oral therapy based on routine group)by ran-dom number table method,with 57 cases in each group.After 6-month treatment,left ventricular hypertrophy de-gree,indexes of oxidative stress,left ventricular remodeling and glucose metabolism were compared between two groups before and after treatment.Results:After 6-month treatment,15 cases were lost and 99 patients were fi-nally included,including 47 patients in the routine group and 52 patients in the dapagliflozin group.After 6-month treatment,compared with routine group,there was significant rise in superoxide dismutase(SOD)level[(33.17±6.05)U/L vs.(37.43±6.22)U/L](P＜0.001),and significant reductions in reactive oxygen species(ROS)[(613.63±36.50)U/ml vs.(597.12±39.85)U/ml],left ventricular end-diastolic volume index(LVEDVI)[(49.31±2.58)ml/m2 vs.(47.60±2.53)ml/m2],left ventricular end-systolic volume index(LVESVI)[(31.18±2.37)ml/m2 vs.(29.44±2.26)ml/m2],left ventricular mass index(LVMI)[(107.93±6.46)g/m2 vs.(104.85±6.19)g/m2],incidence rate of left ventricular hypertrophy(19.15％vs.5.77％),levels of fasting blood glucose(FBG)[(6.33±1.56)mmol/L vs.(5.65±1.42)mmol/L],2h postprandial glucose(2hPG)[(7.35±1.11)mmol/L vs.(6.46±2.10)mmol/L]and glycosylated hemoglobin A1e(HbA1c)[(7.30±1.41)％vs.(6.62±1.29)％]in dapagliflozin group,P＜0.05 or＜0.01.Conclusion:Dapagliflozin on the basis of traditional medication can further im-prove blood glucose,inhibit oxidative stress,delay the process of left ventricular remodeling,and reduce the incidence of left ventricular hypertrophy in patients with type 2 diabetes mellitus and chronic heart failure.

Female ; Glucuronosyltransferase ; biosynthesis ; genetics ; Hepatitis B, Chronic ; enzymology ; Hepatitis C, Chronic ; enzymology ; Hepatitis, Chronic ; enzymology ; Humans ; Liver Cirrhosis ; enzymology ; Male ; RNA, Messenger ; biosynthesis ; genetics

OBJECTIVETo evaluate the protective efficacy of plague subunit vaccine, BALB/c mice, guinea pigs and rabbits were used in this study.

METHODSGroups of mice (10 per group), guinea pigs (14 per group) and rabbits (6 per group) were immunized with F1 + rV270 vaccine, EV76 vaccine and alum adjuvant by intramuscular route, respectively. Serum antibody titres of mice, guinea pigs and rabbits were determined by ELISA and the immunized animals were challenged with 10(6) CFU of Y. pestis strain 141 at the 8th week after the primary immunization.

RESULTSThe immunized mice, guinea pigs or rabbits with subunit vaccine developed anti-F1 IgG titre of 41 587.3 +/- 2.1, 11 543.7 +/- 2.1 or 522.4 +/- 22.4 and elicited statistical anti-F1 IgG titre difference among them (F = 17.58, P < 0.01). The immunized mice, guinea pigs or rabbits with subunit vaccine had anti-rV270 IgG titre of 15 748.7 +/- 1.6, 12.6 +/- 1.4 or 1648.0 +/- 5.0 and induced statistical anti-rV270 IgG titre difference among them (F value was 16.34, P < 0.01). There was significant anti-F1 IgG titre difference among mice, guinea pigs and rabbits immunized with EV76 vaccine that developed anti-F1 IgG titre of 913.4 +/- 4.5, 937.0 +/- 2.0 or 342.0 +/- 12.0 (F = 23.67, P < 0.01), whereas the immunized mice, guinea pigs and rabbits with EV76 vaccine developed anti-rV270 IgG titre of 12.0 +/- 1.0, 447.0 +/- 10.0, 40.0 +/- 11.0 and there was no anti-rV270 IgG titre difference between them (F = 2.20, P = 0.1314). The immunized mice with subunit vaccine developed significantly higher anti-F1 IgG titres than immunized guinea pigs and rabbits (q value was 30.57 and 19.04, respectively, P < 0.01), and there were no anti-F1 IgG titre differences between the immunized guinea pigs and rabbits (q = 0.04, P = 0.8485). The immunized mice with subunit vaccine developed significantly higher anti-rV270 IgG titres than immunized guinea pigs and rabbits (q value was 27.10 and 19.49, respectively, P < 0.01), and there were no anti-rV270 IgG titre differences between the immunized guinea pigs and rabbits with the subunit vaccine (q = 0.25, P = 0.6187). The immunized mice with EV76 elicited higher anti-F1 IgG titres than immunized guinea pigs and rabbits (q value was 40.67 and 29.10, respectively, P < 0.01), whereas there was no difference of F1 IgG titer between immunized guinea pigs and rabbits (q = 0.06, P = 0.8098). The immunized mice, guinea pigs and rabbits with subunit vaccine provided 100% (10/10), 86% (12/14) and 100% (5/5) protection against 10(6) CFU Y. pestis of challenge, respectively. The immunized mice, guinea pigs and rabbits with EV76 vaccine gave 100% (6/6), 93% (13/14) and 100% (6/6) protection against 10(6) CFU Y. pestis of challenge respectively.

CONCLUSIONBALB/c mice is the best small animal model for valuation of protective efficacy of plague subunit vaccine. The guinea pigs showed a high individual variation for this purpose. The rabbits can be used as an alternative model for evaluating plague subunit vaccine.

Animals ; Antibodies, Bacterial ; blood ; Dose-Response Relationship, Immunologic ; Female ; Guinea Pigs ; Immunization ; Immunoglobulin G ; blood ; Mice ; Mice, Inbred BALB C ; Models, Animal ; Plague ; prevention & control ; Plague Vaccine ; immunology ; Rabbits ; Vaccines, Subunit ; immunology

OBJECTIVETo verify the improvement function of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke.

METHODSEighty cases were randomly divided into a warming-reinforcing acupuncture combined with rehabilitation training group (group A) and a rehabilitation training group (group B), 40 cases in each group. Both groups were treated with internal routine treatment. The Motor Relearning Program rehabilitation was used in group B, while warming-reinforcing acupuncture combined with Motor Relearning Program rehabilitation were used in group A. Jianyu (LI 15), Quchi (LI 11), Hegu (LI 4), Yanglingquan (GB 34), Yinlingquan (SP 9), Zusanli (ST 36), Sanyinjiao (SP 6) were selected, and warming-reinforcing method was used in these points, they were treated for 3 weeks. The neurological functional deficits scores of hemiparalysis patients, Fugl-Meyer Score, Motor Function Assessment Score (MAS), Barthel Index and Mini-mental State Examination (MMSE) were used to evaluate the condition of hemiparalysis patients before and after treatment.

RESULTSThe effective rate of group A (87.5%, 35/40) superior to that of group B (67.5%, 27/40) (P < 0.05). The neurological functional deficit scores, Fugl-Meyer score, MAS and Barthel Index of both groups were improved after treatment (P < 0.01, P < 0.05), and the improved degree of group A was better than that of group B (P < 0.01, P < 0.05).

CONCLUSIONThere is obvious improvement function of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke, and the function is better than that of simple rehabilitation training.

Activities of Daily Living ; Acupuncture Therapy ; Adult ; Aged ; Aged, 80 and over ; Brain Ischemia ; complications ; Hemiplegia ; physiopathology ; rehabilitation ; therapy ; Humans ; Male ; Middle Aged ; Motor Activity ; Stroke ; complications ; Treatment Outcome