Background Age-related cataract is one of the common causes of blindness.Although the pathophysiology of age-related cataract is far from clearly understood,it is well accepted that DNA damage plays an important role in the disease pathogenesis.Objective The purpose of this study was to quantitatively evaluate the DNA damage in peripheral lymphocytes of age-related cataract.Methods A cross-sectional study was carried out.This study complied Declaration of Helsinki and approved by Ethic Committee of Affiliated Hospital of Nantong University.Written informed consent was obtained from each subject.Two hundred and eleven patients with agerelated cataract and 147 normal subjects were enrolled from a “ Jiangsu Eye Study:Funing 2011 Eye Disease Epidemic Survey”.All the subjects aged from 50 through 80 years with matched age and gender between the two groups.The percentage of tail DNA and Olive tail moment (OTM) were detected by comet assay to assess the extent of DNA damage in peripheral lymphocytes.Statistical analyses were performed with SPSS 17.0 software,and the differences of the percentage of tail DNA and OTM were compared between the age-related cataract group and normal control group by independent sample t test as well as among the 50-59 years group,60-69 years group and ≥70 years group by one-way analysis of variance.Results Comet assay showed a round lymph cell with the clear border in the normal group;while in the age-related cataract group,the cell was bigger with a comet-like tail.The percentage of tail DNA and OTM in peripheral lymphocytes were (21.75 ± 3.51) ％ and 6.54 ± 1.65 in the age-related cataract group,and those in the normal control group were (9.31 ±3.60)％ and 2.18 ± 1.10,respectively,with significant differences between them (t =32.67,P =0.00 ; t =28.02,P =O.00).In the 50-59 years subgroup of the age-related cataract group,the percentage of tail DNA and OTM in peripheral lymphocytes were (20.04±2.86) ％ and 5.92± 1.14,and in the 60-69 years subgroup of the age-related cataract group,the percentage of tail DNA and OTM in peripheral lymphocytes were (20.77 ±2.93) ％ and 6.13 ± 1.14,which were significantly reduced in comparison with (22.79 ± 3.67)％ and 6.95±1.91 of the ≥70years subgroup(TailDNA％:q=2.75,P=0.00; q=2.02,P=0.00;OTM:q=1.03,P =0.02 ; q =0.82,P =0.00).Conclusions The pathogenesis and development of age-related cataract probably is associated with DNA damage.

AIM:To investigate the effects of 1.8mm coaxial micro incision phacoemulsification on corneal endothelial injury and postoperative visual acuity.METHODS: Totally 145 eyes in 120 patients underwent phacoemulsification from July 2013 to July 2015 were randomly divided into observation group 60 cases (73 eyes) and control group 60 cases (72 eyes).The observation group 60 cases were given 1.8mm coaxial micro incision cataract phacoemulsification operation,while the control group were given traditional 3.2mm coaxial micro incision cataract surgery.The uncorrected visual acuity (UCVA),best corrected visual acuity (BCVA),corneal thickness of incision area,incision width,incision length,macular retinal thickness,surgically induced astigmatism,corneal endothelial cell counts and complications of the two groups were compared.RESULTS: The UCVA and BCVA on 1wk after surgery of the observation group were significantly higher than the control group (t=3.604,7.109;P<0.05);the width of incision on 1wk and 1mo after surgery of the observation group were significantly less than the control group (t=205.3,225.2;P<0.05).The length of incision in observation group was significantly greater than the control group (t=3.926,5.009;P<0.05).Macular retinal thickness 1wk after surgery of the observation group was significantly less than the control group (t=2.817,P<0.05).The surgically induced astigmatism was significantly less than the control group (t=19.43,22.16;P<0.01);the difference of corneal edema between the two groups was not significant (8.22% vs 11.11%) (x2=0.348,P>0.05).CONCLUSION: The 1.8mm micro incision phacoemulsification is helpful to improve the visual acuity of patients with cataract phacoemulsification,which may be related to the reduction of corneal cell injury,enhancement of corneal closure and decrease post-operation corneal original astigmatism.

This study investigated the effect of puerarin on human umbilical vein endothelial cells (HUVEC) injured with hydrogen peroxide (H₂O₂). HUVEC were divided into three groups: a control group, a model group (H₂O₂ 400 μmol·L^-1) and a puerarin-treated group (3, 10, 30 and 100 μmol·L^-1). HUVEC were cultured with varied concentration of puerarin for 2 h and treated with H₂O₂ for another 24 h. Cell proliferation was detected by a CCK-8 assay. The mitochondrial membrane potential was measured by a JC-1 fluorescent probe. A transwell chamber assay was adopted to observe cell migration ability. Mitochondrial respiratory function was measured in a two-chamber titration injection respirometer (Oxygraph-2k). The expression of interleukin-1β (IL-1β), interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) was detected by quantitative real-time PCR. The expression of pyroptosis-mediated proteins, including cleaved-cysteinyl aspartate-specific proteinase-1 (caspase-1), N-gasdermin D (N-GSDMD), NOD-like receptor protein 3 (NLRP3) and purinergic ligand-gated ion channel 7 receptor (P2X7R) was detected by Western blot. The results show that 400 μmol·L^-1 H₂O₂ treatment for 24 h causes obvious damage to HUVEC. Compared with the model group, puerarin protected against cellular injury in a dose-dependent manner, with the greatest effect at a dose of 30 and 100 μmol·L^-1. Puerarin significantly decreased the mitochondrial membrane potential and improved mitochondrial function. Puerarin inhibited cell migration induced by H₂O₂, suppressed the expression of IL-1β, IL-18 and TNF-α, and down-regulated the pyroptosis-mediated protein. These changes are statistically significant (P < 0.05). These findings demonstrate that puerarin has a protective effect against H₂O₂-induced oxidative damage of HUVEC by inhibiting the migration of HUVEC cells. The mechanism may be related to improved mitochondrial respiratory function and inhibition of pyroptosis.

This study was to investigate the protective effects of puerarin on myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanism. The MI/R-model was established by ligating the left anterior descending artery (LAD) for 60 min followed by 24 h reperfusion, puerarin (10, 30, and 100 mg·kg^-1) was orally administered 20 min before reperfusion. Cardiac function, myocardial infarct index, cardiac damage markers, inflammatory cytokines, and apoptosis index were measured to evaluate the protective effects of puerarin on MI/R injury. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome and Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor kappa B (NF-κB) pathway were determined by Western blot. All animal experimental procedures were approved by the ethics committee of the Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences. The results showed that puerarin could significantly improve cardiac function, reduce myocardial infarct size, decease the levels of lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase-MB (CK-MB), and cardiac troponin T (cTnT) and suppress cardiomyocyte apoptosis. Meanwhile, puerarin could notably decrease the levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed that puerarin could downregulate the expression of TLR4, Myd88, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-caspase 1, cleaved-gasdermin-D (GSDMD), IL-1β, and IL-18, as well as the phosphorylation levels of inhibitor of NF-κB α (IκBα), IκB kinase β (IKKβ), and NF-κB. These findings demonstrated that puerarin could alleviate MI/R injury by suppressing NLRP3 inflammasome activation, possibly via TLR4/Myd88/NF-κB pathway.

To investigate the electrophysiological effects of 17β-estradiol on pacemaker cells in sinoatrial (SA) nodes of rabbits and the underlying mechanism, intracellular microelectrode technique was used to record action potential (AP) in SA node cells of rabbits. The results showed that: (1) 17β-estradiol (1, 10, 100 μmol/L) not only significantly decreased the amplitude of action potential (APA) and the maximal rate of depolarization (V(max)), but also decreased the velocity of diastolic (phase 4) depolarization (VDD) and rate of pacemaker firing (RPF) in a concentration-dependent manner. The AP duration at 50% repolarization (APD(50)) and at 90% repolarization (APD(90)) were prolonged. But the maximal diastolic potential (MDP) was not affected. (2) Pretreatment with tamoxifen (10 μmol/L), an inhibitor of estrogen receptor, did not block the electrophysiological effects of 17β-estradiol (10 μmol/L) on SA node cells. (3) Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 μmol/L), a nitric oxide (NO) synthase inhibitor, completely abolished the electrophysiological effects of 17β-estradiol (10 μmol/L) on SA node cells. The results suggest that 17β-estradiol inhibits the electrophysiological activity of pacemaker cells in SA nodes of rabbits in a concentration-dependent manner possibly through a non-genomic mechanism related with NO.
Action Potentials ; Animals ; Electrophysiological Phenomena ; Estradiol ; pharmacology ; Myocytes, Cardiac ; drug effects ; Rabbits ; Sinoatrial Node ; cytology

Objective:To establish a standardized nursing management model for hypoglycemia in diabetic inpatients and observe its application effects.Methods:Totally 9 251 diabetic patients hospitalized in People's Hospital of Zhengzhou between January and December 2017 were selected into the control group, while another 9 636 diabetic patients hospitalized in People's Hospital of Zhengzhou between January and December 2018 were selected into the observation group by cluster sampling. Patients in the control group received routine care and glycemic management. In 2018, in conjunction with the glycemic monitoring system, we established a diabetes education management team and developed a standardized nursing management process for hypoglycemia, which was promoted throughout the hospital to improve the level of hypoglycemic control among nurses throughout the hospital. Patients in the observation group received care and glycemic control using the standardized nursing management model for hypoglycemia and glycemic control. The incidence of hypoglycemia, glycemic fluctuations, and nurses' knowledge of hypoglycemia before and after implementation were compared between the two groups.Results:The incidence of hypoglycemia in the observation group was lower than that in the control group [7.51% (724/9 636) vs. 18.30% (1 693/9 251) ], and the difference was statistically significant (χ 2=492.7, P<0.001) . The observation group's average blood glucose value (GluAve) , daily mean amplitude of glycemic excursions (MAGE) , glycemic instability index (GLI) , and glycemic coefficient of variation (GluCV) were all lower than the control group, and the differences were statistically significant ( t=-18.121, -53.788, -34.362, -61.794; P<0.01) . After the implementation of the standardized management model for hypoglycemia in 2018, the total score dimensional scores of the nurses' knowledge about hypoglycemia were higher than those before the implementation of the standardized nursing process for hypoglycemia in 2017, and the differences were all statistically ( t=15.439, 66.542, 73.320, 14.565, 36.101, 34.664; P<0.01) . Conclusions:The standardized nursing management model for hypoglycemia can reduce the incidence of hypoglycemia as well as fluctuations of the patients, improve the level of nurses' knowledge of hypoglycemia, and make the patients' glycemic control safer.

Objective To investigate the effect of immune modulation therapy on cardiac function and lymphocyte subsets in aged patients with chronic heart failure(CHF). Methods CHF(NYHA classification: Ⅱ - Ⅳ)patients older than 60 years were randomly divided into two groups: CHF intervention group received regular therapy and thymopetidum(2 mg/day i.m. for 75 days, n = 48), CHF control group received regular therapy(n = 48), 45 healthy individuals older than 60 years served as normal control. Left ventricular ejection faction of(LVEF), inner diameter of left ventricular end-diastole(LVEDD), inner diameter of left ventricular end-systole(LVESD), lymphocyte subsets, plasma high sensitive C-reactive protein(hsCRP), plasma brain natrium peptide(BNP)and 6 minutes walking distance(6MWT)were measured at before therapy, after the ftrst course(15 days)of treatment and after the third course of treatment(75 days). Results(1)Before therapy, the levels of BNP, hsCRP, CD8 T cells, LVEDD and LVESD were significantly higher and the levels of CD3,CD4, CD19 T cells, NK, CD4/CD8 ratio, LVEF and 6MWT were significantly lower in CHF patients compared to compared normal controls(all P ＜ 0.05).These parameters were similar between CHF intervention group and CHF control group.(2)At 15 days, the levels of CD3, CD4, CD19 T cells and NK weie signiftcantly increased(P ＜ 0.05 or P ＜0.01)while the level of CD8, BNP and hsCRP were significantly decreased(P ＜ 0.05 or P ＜ 0.01)in CHF intervention group compared with CHF control group.(3)At 75 days, the levels of CD3, CD4, CD19 T cells, NK,CD4/CD8, LVEF and 6MWT were significantly increased(P ＜ 0.05 or P ＜ 0.01)while the levels of CD8,BNP, hsCRP and Minnesota Living with Heart Failure Questionnaire(MLHFQ)were significantly decreased (P ＜ 0.05 or P ＜ 0.01)in CHF intervention group compared with CHF control group. Conclusion Thymopetidum, an immunemodulating agent, might regulate the quantity and proportion of lymphocyte subsets and improve cardiac function in aged patients with CHF, indicating that immune modulation therapy might be a new treatment strategy for aged CHF patients.

BACKGROUNDCentral nervous system leukemia (CNSL) is an important relapse in children with acute lymphoblastic leukemia (ALL). We investigated the possible role of endogenous hydrogen sulfide (H(2)S) of cerebrospinal fluid (CSF) in predicting CNSL.

METHODSFrom August 2008 to December 2010, 380 children were enrolled in this study at Shijitan Hospital, China. These children were from 2 to 16 years old, and the median age was 6.5 years. They were divided into a CNSL group (7 cases), a leukemia group (307 cases), a non-leukemia group (26 cases) and a healthy group (40 children). CSF specimens were obtained from conventional lumbar punctured, then centrifuged and supernatants preserved for H(2)S detection. Leukemic cells precipitates from CSF were found in three cases, the hCSE and hCBS mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR), and H(2)S levels in serum were also measured. The receiver operating characteristic (ROC) curve and area under curve (AUC) were used to assess the predictive diagnosis role of CSF H(2)S in children with ALL and CNSL.

RESULTSThe serum H(2)S contents of the CNSL and leukemia groups were (96.98 ± 15.77) µmol/L and (93.35 ± 17.16) µmol/L respectively, much higher than those of healthy, (44.29 ± 2.15) µmol/L, and non-leukemia, (46.32 ± 6.54) µmol/L, groups (P < 0.01). Compared with the leukemia group, CSF H(2)S content of the CNSL group was significantly high (P < 0.01). Meanwhile, in contrast to the non-leukemia group, CSF H(2)S contents of the CNSL and leukemia groups were both significantly increased (P < 0.01). In addition, leukemic cells from CSF precipitations could express CBS and CSE mRNA. Furthermore, the ROC analysis showed the UAC was 0.929 (95%CI: 0.857 - 1.000), and the optimum cut-off value of CSF H(2)S was 12.08 µ mol/L, and the sensitivity and specificity were 83.3% and 97.2% respectively.

CONCLUSIONSCSF H(2)S contents were significantly increased in children with CNSL. After treatment, H(2)S contents were decreased subsequently. Therefore, we speculated that H(2)S levels of CSF would predict CNSL in ALL children.

Adolescent ; Central Nervous System Neoplasms ; cerebrospinal fluid ; metabolism ; pathology ; Child ; Child, Preschool ; Cystathionine beta-Synthase ; genetics ; Female ; Humans ; Hydrogen Sulfide ; cerebrospinal fluid ; Leukemia ; cerebrospinal fluid ; Lyases ; genetics ; Male

OBJECTIVETo investigate the protective effect of exendin-4 against diabetic cardiomyopathy in mice and explore the underlying mechanism.

METHODSC57BL/6J mice were randomly divided into normal control group with normal diet and diabetic group with high-fat diet for 4 weeks before streptozotocin injection. The successfully established diabetic mouse models were divided into diabetic group with exendin-4 treatment and diabetic control group for daily treatment with intraperitoneal injection of 1 nmol/kg exendin-4 and saline of equivalent volume for 8 weeks, respectively. The physiological parameters such as blood glucose and body weight were recorded. RT-PCR was used to examine the transcription levels of genes related with myocardial hypertrophy and fibrosis and the genes related with mitochondrial functions including PGC1α, NRF and CytoC. The expressions of oxidative stress markers and Sirt1/PGC1 proteins were measured using Western blotting. and HE staining was used to observe the myocardial structural changes in the mice.

RESULTSCompared with the normal control mice, the mice in diabetic control group showed significantly increased blood glucose and blood lipid levels (P<0.001), which were obviously improved by Exendin-4 treatment. The expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 were significantly increased (P<0.05) while Sirt1, PGC1α, NRF and SOD1 expression were markedly decreased in the myocardial tissue of the diabetic mice (P<0.05). Exendin-4 treatment resulted in obviously reduced expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 (P<0.05) and increased expressions of Sirt1, PGC1α, NRF and SOD1 (P<0.05) in the diabetic mice.

CONCLUSIONSExendin-4 protects against myocardial injury in diabetic mice by improving mitochondrial function and inhibiting oxidative stress through the Sirt1/PGC1α signaling pathway.

OBJECTIVE To investigate the effects of total flavonoids of bugloss(TFB)on left ventricular (LV)remodeling after myocardial infarction(MI),LV size and function was compared in mice subjected to left anterior descending coronary artery ligation. METHODS 28 d after MI, the infarcted fraction of the LV and LV mass, systolic and diastolic function were measured. Capillary density and myocyte width in the nonischemic portion of the LV were also determined.RESULTS 28 d after MI,both groups had dilated LVs with decreased fractional shortening and lower ejection fractions. Although the infarcted size of the LV was similar in both groups,LV end-diastolic internal diameter,end-diastolic volume,and mass were lower, but fractional shortening, ejection fraction, and the maximum rate of developed LV pressure(dp/dtmax)were greater in TFB treated mice than in control mice.Impairment of diastolic func-tion, as measured by the time constant of isovolumic relaxation (t) and the maximum rate of LV pres-sure decay(dp/dtmin),was more marked in control mice than in TFB treated mice.Mortality after MI was greater in control mice than in TFB treated mice.In control mice,capillary density and myocyte width in the nonischemic portion of the LV did not differ before and 28 days after MI, whereas in TFB treated mice, capillary density increased and myocyte width declined after MI. CONCLUSION These results suggest that the presence of TFB limits LV dysfunction and remodeling in a murine model of MI in part by decreasing myocyte hypertrophy in the remote myocardium.