As a new strategy for the application of sacubitril/valsartan (LCZ696) in patients with CKD, much evidence showed that it improved the prognosis of patients with CKD. This review summarizes the efficacy and safety of sacubitril/valsartan in physiology, pathology, pharmacology and clinical application by searching Wanfang, CNKI, PubMed and other databases for related articles on the application of sacubitril/valsartan in CKD patients. Although LBQ657, the active product of sacubitril, has a high drug accumulation in patients with moderate, severe renal injury, and ESRD, it is not cleared in hemodialysis, and has very little eliminated in peritoneal dialysis, which does not affect its safety. Compared with angiotensin converting enzyme inhibitor and angiotensin receptor blocker drugs, LCZ696 could increase the blood pressure control rate, improve cardiac function, slow down the decline of glomerular filtration rate, and significantly improve cardiovascular outcomes without more adverse events. Sacubitril/valsartan can be used in all levels of CKD patients complicated with hypertension and/or heart failure, with reliable safety and tolerance.

Objective:To investigate the effect of diabetes mellitus on pulmonary uptake of sevoflurane.Methods:Twenty patients with type 2 diabetes mellitus, aged 40-64 yr, with body mass index of 18.5-22.9 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective surgery with general anesthesia, served as diabetes group (group D). Twenty non-diabetic patients matched by age, gender and surgery were selected as control group (group C). After anesthesia induction and tracheal intubation, sevoflurane was inhaled at a concentration of 2% (oxygen flow 2 L/min). The inhaled concentration (Fi) and exhaled concentration (Fa) at 1, 3, 5, 10, 15, 20 and 30 min of inhalation of sevoflurane were recorded, and the Fa/Fi ratio was calculated.The time required for the Fa/Fi ratio to reach 0.7 was recorded. Results:Compared with group C, the Fa/Fi ratio was significantly increased at each time point, and the time required for the Fa/Fi ratio to reach 0.7 was shortened in group D ( P<0.05). Conclusion:Diabetes mellitus can reduce pulmonary uptake of sevoflurane in the patients.

A 64-year-old male patient with colon cancer received one cycle chemotherapy of oxaliplatin+capecitabine and 7 cycles of oxaliplatin+raltitrexed chemotherapy. There were no interstitial changes in chest CT before operation. After 8 cycles of chemotherapy, the patient developed chest tightness and shortness of breath. Chest CT showed interstitial changes in bilateral lungs, which were considered to be related to oxaliplatin. After 31 days of treatments with drugs such as broad-spectrum antibiotics, glucocorticoids, acetylcysteine, and reduced glutathione, as well as noninvasive ventilator assisted ventilation, oxygen inhalation, and other symptomatic treatments, his symptoms of chest tightness and shortness of breath were relieved, and chest CT showed that interstitial lesions in the bilateral lungs were obviously relieved.

A 64-year-old male patient with colon cancer received one cycle chemotherapy of oxaliplatin+capecitabine and 7 cycles of oxaliplatin+raltitrexed chemotherapy. There were no interstitial changes in chest CT before operation. After 8 cycles of chemotherapy, the patient developed chest tightness and shortness of breath. Chest CT showed interstitial changes in bilateral lungs, which were considered to be related to oxaliplatin. After 31 days of treatments with drugs such as broad-spectrum antibiotics, glucocorticoids, acetylcysteine, and reduced glutathione, as well as noninvasive ventilator assisted ventilation, oxygen inhalation, and other symptomatic treatments, his symptoms of chest tightness and shortness of breath were relieved, and chest CT showed that interstitial lesions in the bilateral lungs were obviously relieved.

The E3 ligase HERC4 is overexpressed in human breast cancer and its expression levels correlated with the prognosis of breast cancer patients. However, the roles of HERC4 in mammary tumorigenesis remain unclear. Here we demonstrate that the knockdown of HERC4 in human breast cancer cells dramatically suppressed their proliferation, survival, migration, and tumor growth in vivo, while the overexpression of HERC4 promoted their aggressive tumorigenic activities. HERC4 is a new E3 ligase for the tumor suppressor LATS1 and destabilizes LATS1 by promoting the ubiquitination of LATS1. miRNA-136-5p and miRNA-1285-5p, expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancer patients, are directly involved in suppressing the expression of HERC4. In summary, we discover a miRNA-HERC4-LATS1 pathway that plays important roles in the pathogenesis of breast cancer and represents new therapeutic targets for human breast cancer.

Objective The study was to investigate the spectrum and incidence of the hot-spot deafness gene mutations from non-syndromic hearing loss(NSHL)in Guizhou province.Methods Genomic DNAs of 356 patients of NSHI in Guizhou were obtained from peripheral blood and a deafness gene test chip was used to screen nine hot spot mutation in the gene GJB2,SLC26A4,GJB3 and mitochondria 12SrRNA.Results Eighty-eight (24.72%)out of 356 patients were found carrying at least one pathogenic gene mutation.Among them,40 patients with the GJB2 mutations were found(11.24%),including 19 cases(5.34%)of homozygous matutions,5 cases(1.40%)of com-pound heterozygous mutations,and 15 cases(4.21%)of single heterozygous mutations.Twenty-nine patients with the SLC26A4 mutations were found (8.15%),including 9 cases(2.53%)of homozygous mutations and 19 cases (5.34%)of single heterozygous mutations.Homogenic mitochondrial 12SrRNA 1555A>G mutations were in 10 patients(2.81%)and 1494C>T mutations in 10 patients (0.56%),and heterogeneous mitochondrial 12SrRNA 1555A>G mutations in 7 patients(1.97%).GJB3 gene c.538C>T heterozygous mutations was found in 1 patients. Conclusion The mutations of GJB2 and SLC26A4 gene are two major pathogenic genes for patients with NSHL in Guizhou province.Our study provides a theoretical basis for the early diagnosis,genetic counseling and treatment of deafness.

Objective The hearing and speech rehabilitation effects by hearing aid use and cochlear implanta‐tion in hearing -impaired children were compared .Methods A total of infants aged from 6 months to 3 years with severe hearing loss of prelingual nature were included .They were divided into 2 groups :group 1 (18 with hearing aids) and group 2 (14 with cochlear implantation) .There was no significant difference in the degree of hearing loss and age between the 2 groups .They received rehabilitation education of the same content for a year .Their unaided and aided thresholds were tested in sound field while the IT -MAIS was used for evaluating hearing ability of two groups before and after 3 ,6 ,9 ,and 12 months of hearing aid use and cochlear implantation .Results In both groups ,hearing were better in aided conditions than those of in unaided ,while those from the cochlear group were significantly improved at more frequencies than those of the hearing aid group .In general ,the longer use and train‐ing ,the better hearing improvement .The mean scores of auditory performance in the cochlear implantation group at 6 months were significantly higher in comparison with those at 3 months (P<0 .05) .There were significant differ‐ences in mean scores between the two groups at 6 ,9 ,12 months after fitting (P<0 .05) .The verbal ability scores ,hearing and speech rehabilitation levels in the cochlear group were higher than those of in the hearing aid group (P<0 .05) .Conclusion For severe hearing loss children ,cochlear implantation could produce more noticeable effects than hearing aids .

Objective To undertake a survey on the prevalence, pathogenic factors and treatment needs of hearing impairment in children under 14 years old in Guizhou province. Methods Using the probability proportion to size (PPS) method, 2 068 children aged 0～14 years were included in the study and in 30 clusters in Guizhou province based on the WHO protocol. Results For children aged 0～14 years, the prevalence of hearing impairment was 3.48% and the prevalence of hearing disability was 1.84 %. There were statistically differences of the prevalence of hearing disability between children aged 7～ 14 years (2.66 %) and 0～ 6 years (0. 51%), and the differences also in hearing impairment between male children (4.22%) and female children (2.54%). The main causes of hearing impairment were ear diseases (50.00%), non-infective conditions (11.11%), genetic conditions (20.83 %) and unknown causes (27. 77%). 3. 58% of all subjects needed medical or surgical treatment and 2. 32% needed hearing aids. Conolusion The prevalence of hearing disability of children under 14 years old in Guizhou province was higher than that of other cities. The main cause of the hearing impairment of children was otitis media with hereditary deafness also ranked in top.

Objective To investigate the role of hydrogen sulfide (H2S) synthases/H2S pathway in the pathogenesis of renovascular hypertension.Methods Wistar rats were subdivided into 4 groups:(1) 2-kidney,1-clip (2K-1C group,n=7),(2) control (n=7),(3)sham (n=7),and (4) 2K-1C plus sodium hydrosulfide (NariS) (NariS-treated group,n=7).The systolic blood pressure (SBP) was measured by a tail-cuff method using a pulse transducer once a week.Four weeks later,all rats were killed and the concentration of plasma hydrogen sulfide (H2S),the activity of the H2S syntha.ses in the kidneys on both sides,the plasma angiotensin Ⅱ concentration,and the left-to-whole heart weight ratio were measured.Results The SBP was significantly increased in the 2K-IC group (185.4± 14.0mmHg) comparing with those in the sham group (112.9±6.5mmHg,,or the NariS-treated group(134.8±9.5mmHg) (both P＜0.01).At 4 weeks,the angiotensin Ⅱ concentration in the plasma was increased in the 2K-1C and NariS-treated group,comparing with the control and the sham group (306.92±7.03 pg/ml and 240.73±13.22 pg/ml vs 122.6±25.49 pg/ml and 125.95±10.55 pg/ml,respectively,both P＜0.05).The plasma H2S concentration and the activity of H2S synthases in the left kidney were decreased in the 2K-1C group comparing with those in the sham and the control groups.There was no difference of the activity of the H2S synthases in the right kidneys among the 4 groups.The left-to-whole heart weight ratio was increased in the 2K-1C and the NariS-treated group camparing with that in the sham and natural control groups.Conclusions Dysfunction of the H2S synthases/H2S pathway was involved in the 2K-1C-induced renovascular hypertension in rat.Exogenous administration of H2S donor can attenuate the development of hypertension.These findings suggest that the H2S synthases/H2S pathway participates in the pathogenesis of renovascular hypertension.

OBJECTIVE: To undertake a population-based survey on the prevalence, pathogenic factors and medical requirements of ear and hearing impairment. METHOD: Using the probability proportion to size (PPS) method, 6626 residents were investigated in 30 clusters with the WHO protocol. RESULT: The prevalence of hearing impairment was 17.1% (the standardized rate: 17.6% in the whole country). Degrees of hearing impairment were mild (11.0%), moderate (4.2%), severe (1.4%), and profound (0.5%). Among them, male were 663(20.2%) and female were 468 (14.0%). The prevalence of hearing disability was 6.1% (the standardized rate: 6.5% in the whole country). The causes of hearing impairment were ear disorders (31.4%), non-infectious (42. 5%), genetic condino (6.7%), infectious disease (0.4%) and undetermined cause (29.3%). 13.8% of person needed otology and/or audiology actions. 9.1% of person needed hearing aid. CONCLUSION The prevalence of hearing impairment and hearing disability is higher than last twenty years and it can provide scientific data for drawing up precaution and control strategies on deafness for government.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Ear Diseases ; epidemiology ; Female ; Hearing Disorders ; epidemiology ; Humans ; Infant ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Young Adult