Objective:To investigate the efficacy and major adverse cardiovascular events(MACE)in elderly patients with ischemic cardiomyopathy-induced heart failure with reduced ejection fraction(HFrEF)treated with Sacubitril-valsartan at 3 years of follow-up.Methods:This was a single-center retrospective cohort study.The elderly patients with ischemic cardiomyopathy-induced HFrEF aged 60-85 years were diagnosed and treated in Beijing Anzhen Hospital from January 2018 to January 2020.A total of 120 continuously included elderly HFrEF patients treated with sacubitril valsartan were enrolled as the observation group, and 120 age-, gender-and B-type natriuretic peptide-matched elderly HFrEF patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blocker(ACEI/ARB)were enrolled as the control group.Structure and function of the heart were detected at 1-year follow-up.The MACE was observed, including cardiogenic death, readmission due to heart failure worsening and malignant arrhythmia at 3-year follow-up.Results:During follow-up(23.5±11.6)months, the visit of 18 cases was lost.There were no significant differences in the age, medical history, blood pressure between the two groups( P>0.05). Follow-up results showed that the improvement was better in observation group than in control group as follows: the left ventricular ejection fraction(45.8±9.4)% vs.(40.7±8.5)%, left ventricular end-diastolic diameter(56.5±8.3)mm vs.(59.2±7.3)mm, left ventricular end-systolic diameter(42.5±11.2)mm vs.(45.7±9.6)mm, left atrium inner diameter(49.1±8.7)mm vs.(51.2±7.7)mm, and left ventricular mass index(111.3±34.3)g/m 2vs.(119.7±31.5)g/m 2( t=4.41, 2.68, 2.38, 1.98 and 1.98, respectively, P<0.01 or 0.05). The rates of readmission due to heart failure worsening and the incidence of MACE were lower in the observation group than in the control group(21.7% or 26/120 vs.36.7% or 44/120, and 45.0% or 54/120 vs.71.7% or 86/120, χ2=6.54 and 17.55, P<0.05 or 0.01). In patients with the grade Ⅲ and Ⅳ New York Heart Association(NYHA)cardiac function, the incidence of MACE were lower in the observation group than in the control group(75.0% or 9/12 vs.100.0% or 14/14, χ2=5.10, P<0.05). Conclusions:Sacubitril-valsartan can improve cardiac structure and function, and decrease the incidence of MACE in elderly patients with HFrEF induced by ischemic cardimyopathy.

Sixty-eight cases of naevus fusco-caeruleus zygomaticus were observed from 1990 to 1996 in our clinic. In order to differentiate easily from other pigmented disorders, detailed analysis was carried out. The results showed that this condition principally occurred in young or middle-aged women, manifested as dark greyish spots scattered bilaterally and symmetrically on the zygomatic region. Histopathologically, there were elongated, slender spindle-shaped melanocytes scattered in the upper portion of the dermis, their long axes run parallel to the collagen fibres. It suggests that the naevus reported differs clinically and histopathologieally from naevus of Ota.

cases of vitreous haemorrhage secondary to Eales′ disease were selected for vitrectomy. According to the duration of vitreous haemorrhage, the patients were divided into two groups : Group 1 (20 eyes)-early vitrectomy group with a duration between 3 to 6 months; Group 2(20 eyes)-deferred vitrectomy group with a duration of more than 6 months . All the patients were followed up for a minimum period of 3 months following vitrectomy. The eyes in Group 1 showed a preoperative ultrasonic picture of complete posterior detachment, a final visual acuity of 0.6 or better in 13(65%) was achieved in mild vitreous organization on kinetic echography. Poor visual outcome in the deferred group was secondary to cystoid macular oedema, macular scar, macular pucker formation and macular degeneration. Improved visual outcome in the early vitrectomy group is probably due to haemorrhage and its products which have no time to damage the macula and to advance into macular traction and cystoid macular oedema.

Objective To investigate the serum levels of CXC, CC and C chemokines, and to esti-mate the relationship among the three kinds of chemokines as well as that between these chemokines and other Th1 and Th2-related cytokines, in patients with atopic dermatitis (AD). Methods Fifty-one patients with atopic dermatitis, including 35 males and 16 females with an average age of 17 years and disease course of 13.6 years were enrolled into this study together with 34 normal human controls. ELISA was used to measure the serum levels of monokine induced by IFN-γ (Mig), thymus and activation-regulated chemokine (TARC), cutaneous T cell-attracting chemokine (CTACK) and lymphotactin (Ltn) in these subjects. Severity of AD was assessed according to SCORAD. Results The serum levels were 79.6±28.0 ng/L for Mig, 349.9±91.5 ng/L for TARC, 747.4±359.4 ng/L for CTACK and 141.0±68.4 ng/L for Ltn in patients, significantly higher than those in the normal controls (63.8±26.5 ng/L, 219.4±82.1 ng/L, 294.3± 64.9 ng/L, 80.9±54.2 ng/L, P < 0.05, 0.01, 0.01, 0.01 respectively). A significant correlation was observed between the serum level of CTACK and SCORAD score in patients (r = 0.343, P < 0.05). Similarly, the percentage of body surface area (BSA) involved positively correlated with the serum levels of Mig, TARC, CTACK and Ltn. Furthermore, there was a significant correlation between the serum level of Ltn and TARC (r=0.444, P< 0.01) as well as CTACK (r=0.572, P< 0.01), between that of CTACK and TARC (r=0.524, P< 0.01), and between that of TARC and Mig (r=0.313, P< 0.05). Conclusion The CXC, CC and C chemokines might be involved in the pathogenesis of AD. Further more, CTACK level could serve as a good indicator for the severity of AD.

Objective To determine the effect of NS3 and NS4A proteins of Zika virus on the neuronal migration in vivo.Methods To identify the coding sequence of NS3 and NS4A,the genome of Zika SZ01 was sequenced by rapid amplification of cDNA ends (RACE) and reverse-transcription PCR,then NS3 and NS4A was constructed in pCIG vector fused with Flag-tag to express these proteins.And then these plasmids was transfected into the embryo brain of E13.5 mice by in utero electroporation,the distribution of the cells which express these proteins in the cortex was detected by Flag,eGFP and TBR1 fluorescence in E18.5 mice through immunohistochemistry so as to assess the influence of viral proteins on the neuronal migration of mouse cortex.Results 1) Sequence results showed that the amino acid sequence of NS4A is consistent with NCBI data,while NS3 has 1 amino acid mutant.2) As the fluorescence of Flag and eGFP can co-localization,the eGFP fluorescence signal marks the cells that have expressed these virus proteins in cortex.3) TBR1 fluorescence shows the distribution of the cells that express NS4A in vivo are significantly different from pCIG control and NS3 (P＜0.001).Conclusions The NS4A protein of Zika virus may affect the neuronal migration in vivo.

Objective To detect the levels of oxidative stress in brain and serum of rats with chronic fluorosis and the antagonistic effects of vitamin E (VitE),and to reveal the role of oxidative stress in brain injury.Methods Thirty healthy SD rats were divided into three groups based on body weight by means of a random number table (10 rats in each group,half male and half female).In the control group,the rats were fed with drinking water containing less than 0.5 mg/L fluoride;in the fluoride group,the rats were fed with high doses of sodium fluoride in drinking water (50.0 mg/L) and the VitE antagonistic group were fed with the same content of fluoride in drinking water as the fluoride group,but adding VitE (50.0 mg/kg) by intragastric administration once a day.All rats were fed with normal diet (6.2 mg/kg).After exposure to fluoride for 10 months,all rats were put to death,dental fluorosis of the rats was examined and the fluoride content in bone was determined by fluoride-ion selective electrode;the activity of superoxide dismutase (SOD) was determined by the xanthine oxidase method and glutathione peroxidase (GSH-Px) by the colorimetric method,the level of malonaldehyde (MDA) by the glucosinolates barbituric acid fluorescence method and the levels of OH-,H2O2 and O-·2 in rat serum and/or brain were detected by the colorimetric method.Results In the rats of the fluoride group,fluoride content in bone was higher as compared to control [bone fluoride:(211.07 ± 48.52) vs.(33.40 ± 9.26) mg/kg,P ＜ 0.01].The activities of SOD and GSH-Px in rat brains of the fluoride group [(20.10 ± 1.98) kU/g,(28.70 ± 19.35) kU/L] were significantly lower than those of controls [(37.05 ± 3.13) kU/g,(59.63 ± 12.83) kU/L,all P ＜ 0.01],the activity of SOD in VitE antagonistic group [(26.27 ± 1.74) kU/g] was higher than the fluoride group (P ＜ 0.01);the activities of SOD and GSH-Px in rat serum of the fluoride group were significantly decreased [(11.55 ± 1.75) kU/L,(79.50 ± 19.18) U/L] than those of controls [(20.79 ± 2.43) kU/L,(170.00 ± 14.68) U/L,all P ＜ 0.01],the activity of SOD in VitE antagonistic group [(17.23 ± 0.68) kU/L] was higher than the fluoride group (P ＜ 0.01).The levels of MDA in rat brain and serum of the fluoride group [(8.84 ± 0.69) μmol/L,(1.46 ± 0.11) nmol/L] were significantly higher than those of controls [(1.27 ± 0.74) μmol/L,(0.83 ± 0.10) nmol/L,all P＜ 0.01],VitE antagonistic groups [(4.51 ± 1.13) μmol/L,(1.29 ± 0.02) nmol/L] were lower than the fluoride groups (all P ＜ 0.01).The levels of OH-,H2O2 and O-·2 in rat brains of the fluoride group [(24.24 ± 1.80) kU/g,(15.28 ± 2.97) mmol/L,(6.53 ± 0.96) U/g] were significantly higher than those of controls [(11.44 ± 1.63) kU/g,(5.28 ± 1.20) mmol/L、,(2.93 ± 0.42) U/g,all P ＜ 0.01],VitE antagonistic groups [(14.43 ± 0.76) kU/g,(8.09 ± 0.55) mmol/L,(4.41 ± 0.49) U/g] were lower than the fluoride groups (all P ＜ 0.01).Conclusions Elevated levels of oxidative stress are found in brain and serum of the rats with chronic fluorosis,which may be a main mechanism of brain injury.VitE may play an important antagonistic role in oxidative damage induced by fluoride toxicity.

Objective To observe the expression of NF-E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein-1 (Keap1) at mRNA and protein levels in the brain of rats with chronic fluorosis and to reveal the mechanism of brain damage induced by the factors.Methods Ninety SD rats were divided into three groups (30 rats in each group,half male half female) by the random number table method according to body weight.The control group was fed with normal tap-water,high-fluoride group with 50 mg/L fluoride (NaF) added in drinking water;and the high-fluoride plus vitamin E (Vit E) group with the same dose of NaF as the high-fluoride group,but giving 5 mg/kg Vit E by intragastric administration.The experiment period was 10 months.The fluoride contents in urine and bone were detected by fluoride-ion selective electrode.The protein and mRNA levels of Nrf2 and Keap1 in brain of rats were detected by Western blotting and quantitative real time PCR,respectively.The activity of superoxid dismutas (SOD) and the content of lipid peroxidation (MDA) were measured by biochemistry methods.Results Dental fluorosis was detected in high-fluoride group.The differences of fluoride contents in urine and bone were statistically significant between groups (F =6.87,182.87,all P ＜ 0.05).The urine fluoride [(2.16 ± 0.39),(2.07 ± 0.15)mg/L] and bone fluoride [(211.07 ± 40.52),(82.09 ± 28.60)mg/kg] in the high-fluoride and high-fluoride plus Vit E groups were higher than those of the control group [(1.70 ± 0.24)mg/L,(34.67 ± 11.15)mg/kg,all P ＜ 0.05].The differences of mRNA and protein levels of Nrf2 and Keap1 in brains of rats,SOD activity,MDA content were statistically significant between groups (F =654.33,432.87,447.45,398.88,68.34,68.34,all P ＜ 0.05).The mRNA levels of Nrf2 and Keap1 [(320.18 ± 6.83)％,(267.37 t 7.22)％] were increased compared to those of control group [(100.00 ±3.00)％,(100.00 ± 2.75)％,all P ＜ 0.05];the protein levels of Nrf2 and Keap1 [(283.28 ± 6.89)％,(196.32 ± 5.57)％]were also raised compared with those of control group [(100.00 ± 8.71)％,(100.00 ± 9.23)％,all P ＜ 0.05];the activity of SOD [(22.10 ± 2.10)μ,mol/kg] in brain of rats in fluoride group was significantly lower and the content of MDA [(8.63 ± 0.77) μmol/kg] was higher than those of control group [(35.05 ± 2.98),(1.25 ± 0.64) μmol/kg,all P ＜ 0.05].In high-fluoride plus Vit E group,the mRNA levels of Nrf2 and Keap1 [(243.23 ± 5.34)％,(180.54 ± 4.48)％] and the protein levels of Nrf2 and Keap1 [(210.88 ± 4.79)％,(150.68 ± 6.49)％] were lower than those of high-fluoride group (all P ＜ 0.05);the activity of SOD [(26.33 ± 1.84)μmol/kg] was significantly higher and the content of MDA [(4.88 ± 0.84)μmol/kg] was lower than that of high-fluoride group (all P ＜ 0.05).Correlation analysis showed that increased levels of Nrf2 and Keap1 were positively correlated with the level of MDA in rat brain (r =0.69,0.33,all P ＜ 0.05),but negatively correlated with the activity of SOD (r =-0.78,-0.80,all P ＜0.05).Conclusion The expression of Nrf2 and Keap1 in brain of rats with fluorosis is significantly increased and positively correlated with the content of fluoride in bone and the level of oxidative stress,whereas vit E can attenuate these abnormal changes induced by fluoride,which might be one of the mechanisms of brain damage of the disease.

Objective To report a consanguineous family with lamellar ichthyosis and to detect the mutations in transglutaminase 1 (TGM1) gene in this family. Methods Genomic DNA was extracted from the blood samples of a 19-year-old male patient with lamellar ichthyosis, his family members and 100 normal human controls. PCR was carried out to amplify all the encoding sequences (15 exons) and adjacent flanking sequences of TGM1 gene followed by bidirectional sequencing. Results A C1666T mutation in the 11th exon in TGM1 gene, which resulted in the substitution of ACA (threonine) by ATA (isoleucine) at codon 529, was detected in the proband, while both his parents carried the C1666T mutation in heterozygous form, and his sister was a C/C homozygote. None of the 100 normal control individuals carried the mutation in TGMlgene. Conclusions The de novo mutation from ACA (threonine) to ATA (isoleucine) at codon 529, may contribute to the development of lamellar ichthyosis. Consanguineous marriage can increase the risk for lamellar ichthyosis by raising the probability of homozygosis of C 1666T mutation in TGM 1 gene.

To investigate the effect of Yisui Jiedu Recipe (YSJDR), a compound traditional Chinese herbal medicine, on cytokines and their corresponding just another kinase 2-signal transducers and activators of transcription 5 (JAK2-STAT5) signal transduction pathway in bone marrow hematopoietic cells from patients with myelodysplastic syndrome-refractory anemia (MDS-RA).

Objective To study the effect of chronic fluorosis on neurobehavioral development,the ability of learning and memory in offspring of rats,and the antagonistic effect of antioxidant Vitamin E (Vit E).Methods According to body weight,forty-five 1-month-old Sprague-Dawley(SD) rats of 30 females and 15 males were divided into three groups by random number table,including control group,fluorosis and Vit E antagonistic groups (15 rats with 10 females and 5 males in every group).Five months after establishing the animal model with chronic fluorosis and Vit E gavage treatments (fluoride ＜ 1,50,50 mg/L,respectively; Vit E 0,0,50 mg/kg,respectively),the rats were mated in 2:1 proportion of female:male in different groups,respectively.The fertility index of female and neurobehavioral development indicators in offspring were observed.Spatial learning and memory of offspring after birth for 30 d were evaluated by using Morris Water Maze test.Results The female fertility index exposed to fluorosis and Vit E were not significantly different as compared to those of control group(all P ＞ 0.05) ; in contrast to control groups[(6.4 + 1.8),(15.1 + 1.7)d],the time that completed the surface righting reflex [(8.1 + 1.4),(7.9 + 1.5)d] and the air righting reflex [(17.7 + 2.3),(17.2 + 1.8)d] were delayed in the offspring in fluorosis and Vit E antagonistic groups(all P ＜ 0.05) ; the completed avoidance precipice reflex and the auditory consternation did not changed significantly(all P ＞ 0.05); In addition,compared with control and Vit E antagonistic groups [(31.74 + 17.78),(34.97 ± 15.44)s,(4.50 ± 2.51),(3.80 ± 1.87)time],the average escape latency and exploration platform at five days were decreased in 30 d offspring of fluorosis group[(42.03 + 16.45)s,(2.20 + 1.62)time].Conclusion Neurobehavioral development as well as learning and memory ability in rat offspring are impaired by long-term exposure to fluoride and Vit E has exhibited an antagonistic effect to the toxicities of fluoride.