To investigate the effect of losartan on the axis of prolylcarboxypeptidase (PRCP)--kallikrein of the two-kidney, one-clipped (2K1C) hypertensives rats, and explore the novel protection mechanism of losartan on the kidney. Sprague-Dawley (SD) rats were used to develop the 2K1C hypertensive rats. Then, the rats were treated with prazosin (5 mg x kg(-1) x d(-1)) or losartan (5, 15 and 45 mg x kg(-1) x d(-1)) or vehicle, separately. At the same time, the blood pressures were observed. After treated for four weeks, the ratio of right kidney weight and body weight, the change of glomerular morphology, and K+, Na+, creatinine and blood urea nitrogen (BUN) of the serum were used for evaluation of kidney. The expressions of PRCP mRNA in the kidneys were determined by RT-PCR. The protein levels of PRCP, tissue kallikrein, plasma kallikrein, TGF-beta1 in kidney or plasma were measured by Western blotting. Results showed that the changes of body weight and kidney weight ratio, glomerular fibrosis degree and the biochemistrical index of serum induced by hypertension were relieved when the hypertensive rats treated with losartan for four weeks. Meanwhile, treatment of losartan also significantly decreased expression of TGF-beta1 and increased expressions of PRCP, plasma kallikrein and tissue kallikrein. The protective effects of losartan on the kidney of 2K1C hypertensive rats are activation of the axis of PRCP-kallikrein and reducing the expression of TGF-beta1.

Objective To investigate the effect of hyperoxia on growth of type Ⅱ alveolar epithelial cells (AECⅡ).MethodsLungs of fetal rats at 19 days of pregnancy were collected,and AEC Ⅱ was isolated and cultured by differential adherence method.Cells were randomly divided into air group and hyperoxia group.In air group,cells were cultured in 5％ CO2 incubator.And cells in hyperoxia group were cultured in 5％ CO2+95％ O2 incubator.The growth,activity,cell cycle,cell apoptosis of AEC Ⅱ were observed at 2,4,6 and 8 days of culture.The interaction between different time and groups were analyzed by ANOVA of factorial design.Comparison of means was done by two-sample independent t test and one-way analysis of variance.Bonferroni correction was used during the comparisons.Results(1) Cell growth situation:in hyperoxia group,cell number was decreased from2 hto 8 h [(7.29±0.43)×105/ml,(2.68±0.37)×105/ml,(0.23±0.10)×105/ml and (0.00±0.00) × 105/ml],and lower than those in air group [(10.41 ± 0.24) × 105/ml,(27.90±1.91) × 105/ml,(27.12±0.85) ×105/ml and (26.29±1.59) × 105/ml](t=10.992,38.912,94.166and 49.696,P=0.000 respectively). (2) Cell activity:the living cells ratio in hyperoxia group at 2 d[(79.00±0.71) ％],4 d [(52.80±1.14)％] and 6 d [(31.60±1.52)％] was lower than those [(97.00±0.71)％,(97.20±0.84)％ and (95.00±0.71)％] ir air group (t=31.213,70.519 and 84.722,P=0.000 respectively).(3) Cell cycle:the cell ratios of G1 phase and S phase in hyperoxia group at day 4 [(66.82±1.20) ％ and (27.31±1.16) ％] and day 6 [(70.22±1.27) ％ and (30.31±1.40) ％] were significantly higher than that at day 2 and that in air group (P＜0.05 respectively).(4) Cell apoptosis:in hyperoxia group,the cell ratio of Annexin-V+/PI- subgroup at 4 h was the highest [(23.89 ± 0.52)％],followed by those at day 2 and 6 [(21.32 ± 0.43)％ and (1.47 ±0.61)％].While the cell ratio of Annexin-V+/PI+ was the highest at 6 h [(53.92± 1.64)％],followed by those at 4 h and 2 h [(45.03±1.01)％ and (12.17±0.60)％],which were all different with those in air group(P＜0.05 respectively).ConclusionsHyperoxia might inhibit cell activity and cell cycle of AEC Ⅱ and promote apoptosis.

Objective: To observe the morphologic changes of pituitary adrenocorticotrophic hormone (ACTH) cells in Wistar rats at different altitudes, and clarify the mechanism of stress reaction to hypoxia in ACTH cells. Methods: Wistar rats were divided into three groups and moved to different altitudes (1700 m, 3100 m, 4050 m). After 12 days, changes of ACTH cells were observed by using immunohistochemisty, image analysis and electron microscopy. Results:The ratio (R) of immunoreactive cell area to scanned area and mean optical density (A) increased at higher altitude with statistically different R values between groups of 1700 m and 4050 m (P

Objective To study the differentiation and proliferation ability of the spinal neural stem cells (NSCs) at different gestational ages in fetal rats. Methods Sprague-Dawley fetal rats were divided into group A (12 days of pregnancy), group B (14 days of pregnancy) and group C (16 days of pregnancy). NSCs were separated with enzyme-assisted microdissection. The diameter and numbers of NSCs balls were measured at different time. The cell growth curve was drawn with CCK8 colorimeter. NSCs were identified with BrdU/Nestin immunohistochemical staining. They were induced with 10% fetal bovine serum for 10 days, and the expression of β-tubulinⅢ and glial fibrillary acidic protein was detected with immunocytochemistry. Results There were cells expressed BrdU, Nestin, β-tubulinⅢ and GFAP in all the group. The most cells (22.74±0.79%) expressed β-tubulinⅢ in the group B, but no significant difference between group B and group C. The cell vitality on the 5th day of third-generation neural stem cells was the most in group B. Conclusion For enzyme-assisted microdissection, it may obtain more neurons to isolate the neural stem cells from 14 days of pregnancy pregnant rats.

Objective To investigate clinical characteristics of elderly patients with sepsis combined with congestive heart failure and risk factors for short-term mortality.Methods Clinical data of elderly patients with sepsis combined with congestive heart failure who were admitted in our hospital from January 2013 to January 2018 were selected and retrospectively analyzed.They were divided into the survival group(n=134)and the death group(n=83)according to survival status during hospitalization.The clinical characteristics and risk factors for mortality were analyzed and compared.Results A total of 217 elderly patients were enrolled,with 113 males and a mean age of(72.3 ± 7.5)years.The death rate of sepsis was 38.3％ (83/217 cases),and 29 cases died of sepsis and 54 cases died of other diseases.Pneumonia accounted for 78.8％ (171/217 patients) in all patients of two groups,and skin and soft tissue infection for 12.9 ％ (28/217 cases).There were significant differences between two groups in age,body mass index,smoking,diabetes,chronic obstructive pulmonary disease,mean arterial pressure,arterial oxygen partial pressure(PaO2),C-reactive protein,white blood cell counts,neutrophil and lymphocyte counts,glomerular filtration rate,serum sodium level,albumin level,lactate level,and left ventricular ejection fraction(P ＜0.05).Furthermore,the rates of invasive mechanical ventilation and continuous renal replacement therapy were higher in the death group than in the survival group(x2=13.209 and 7.402,P＜0.001 and 0.007).Multivariate Cox regression analysis showed that advanced age,chronic obstructive pulmonary disease,low albumin level and low glomerular filtration rate were risk factors for mortality(P＜0.05).Conclusions Elderly patients with sepsis combined with congestive heart failure often have severe pneumonia and violent skin and soft tissue infection,with worse heart and renal function.Advanced age,chronic obstructive pulmonary disease,low albumin level and low glomerular filtration rate are risk factors for mortality.

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

The Chinese Guidelines on Diagnosis and Management of Atrial Fibrillation, jointly formulated by the Chinese Society of Cardiology, Chinese Medical Association and the Heart Rhythm Committee of Chinese Society of Biomedical Engineering, was first released on June 15, 2023. The guidelines elaborate the various aspects of atrial fibrillation management, in which emergency management of atrial fibrillation is also an integral part. This article interpreted the emergency management part in the guidelines in detail by reviewing relevant literature.

The World Health Organization (WHO) released the “Global report on hypertension” on September 19, 2023. This report systematically summarizes the prevalence, mortality, diagnosis and treatment of hypertension in various countries, and elucidates the current situation of hypertension management, and gives a series of suggestions on how to manage hypertension, providing new thinking and inspiration for countries to optimize hypertension management. Through the summary of relevant studies and reports, this paper further reviews the present situation, early identification and management of hypertension.