AIM: To investigate the antioxidant effect of hydralazine under hypoxia-induced damage on retinal pigment epithelial (ARPE-19) cells and the role of reactive oxygen species (ROS) in this effect.METHODS: Human retinal pigment epithelial (hRPE) cells were used to investigate the effect of hydralazine on oxidative stress, including tert-butyl hydroxyperoxide (t-BHP), H2O2, sodium azide (NaN3), and hypoxia induced cell damage. Cell viability was determined by MTT assay.RESULTS: When ARPE-19 cells were treated with oxidative stress induced by ROS, hydralazine showed concentration-dependent protection against t-BHP, H2O2 and hypoxia induced cell damage but not NaN3. Nitric oxide (NO) was not involved in this effect.CONCLUSION: Hydralazine showed antioxidant potential against oxidative stress induced damage in ARPE-19 cells. These effects might be caused through scavenger of ROS. Thus, hydralazine could be used for the treatment of age-related macular degeneration (AMD).

Aged ; Female ; Humans ; Iatrogenic Disease ; Lacerations ; etiology ; Pneumoperitoneum ; etiology ; therapy ; Trachea ; injuries ; Tracheostomy ; adverse effects ; instrumentation ; Treatment Outcome

Nephrotic syndrome is a disorder of the glomerular filtration barrier, and central to the filtration mechanism of the glomerular filtration barrier is the podocyte. We are starting to better understand how this cell, with its unique architectural features, fulfils its exact filtration properties. The multiprotein complex between adjacent podocyte foot processes, the slit diaphragm, is essential to the control of the actin cytoskeleton and cell morphology. Many of the proteins within the slit diaphragm, including nephrin, podocin, transient receptor potential-6 channel, and alpha-actinin-4, have been identified via genetic studies of inherited nephrotic syndromes. Signaling from slit diaphragm proteins to the actin cytoskeleton is mediated via the Rho GTPases. These are thought to be involved in the control of podocyte motility, which has been postulated as a focus of proteinuric pathways. Nephrotic syndrome is currently treated with immunosuppressive therapy, with significant adverse effects. These therapies may work in nephrotic syndrome due to specific effects on the podocytes. This review aims to describe our current understanding of the cellular pathways and molecules within the podocyte relevant to nephrotic syndrome and its treatment. With our current knowledge of the cellular biology of the podocyte, there is much hope for targeted therapies for nephrotic syndromes.
Actin Cytoskeleton ; Diaphragm ; Filtration ; Foot ; Glomerular Filtration Barrier ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; Nephrotic Syndrome ; Podocytes ; Proteins ; Proteinuria ; rho GTP-Binding Proteins

AIM: To investigate the mechanism of proliferation effect induced by (R,R)-XY-10 and (S,S)-XY-10 on retinal pigmented epithelial cells(ARPE-19).METHODS: Human retinal pigmented epithelial cells(ARPE-19) and human umbilical vein endothelial cells (HUVECs) were used to investigate the effect of (R,R)-XY-10 and (S,S)-XY-10 on cell growth,and their mechanisms of proliferative action by using ERK、 AKT、PI3K、Protein kinase C (PKC)and Nitric oxide synthase (NOS) inhibitors.RESULTS: (R,R)-XY-10 and (S,S)-XY-10 dose-dependently increased ARPE-19 cell proliferation,but not on HUVECs. When treated with proliferative inhibitors,H7(5μmol/L)、hypericin(20μmol/L)、PD98059(2μmol/L)、LY294002(50μmol/L)、SH-5 (10μmol/L) and L-NAME (100μmol/L),the proliferative effect was reduced by H7、hypericin、PD98059 and LY294002,but not by SH-5 and L-NAME.CONCLUSION: (R,R)-XY-10 and (S,S)-XY-10 can induce cell proliferation through MAPK and PI3K dependent pathway. KEYWORDS: age-related macular degeneration; (R,R)-XY-10; (S,S)-XY-10; ARPE-19 cells; human umbilical vein endothelial cells; proliferation

AIM: To investigate the effect of Z,E-butylidedephthalide (Bdph) on laser-induced experimental choroidal neovascularization (CNV) in rat model and choroid blood flow in rabbits'eyes.METHODS: Male Brown Norway rats were treated with Nd:YAG laser to break Bruch's membrane. Thirty mg/kg and 15 mg/kg Bdph were given daily through intraperitoneal injection for 4 weeks after laser treatment. Fluorescein angiography (FA) and choroidal flat mount were used to measure the development of CNV. Female New Zealand white rabbits' eyes were instilled with 10g/L Z,E-butylidenephthalide solution,and ocular blood flow was measured with colored microsphere technique. RESULTS: The intensity of fluorescein leakage, indicating the ocular lesion, decreased significantly in group Bdph 30mg/kg and 15mg/kg, as compared to the control at P＜0.01.The area of neovascularization checked by FA in both groups of Bdph, at 30mg/kg and 15mg/kg decreased significantly compared to the control group at P＜0.05. On the choroid flat mount, the areas of CNV were also smaller in both Bdph groups than in control group. One percent Z,E-butylidenephthalide solution instilled into rabbits' eyes could improve the choroid blood flow at 30 and 60 minutes after drug instillation (P＜0.05).CONCLUSION: Z,E-butylidedephthalide could inhibit the development of CNV in the rat eyes and increase the choroid blood flow in the rabbit eyes. These results suggest that Z,E-butylidedephthalide may be a good agent for the treatment of age-related macular degeneration(ARMD).

OBJECTIVETo assess the effect of stapes surgery on advanced otosclerosis (AO).

METHODSIn 300 cases randomly collected of otosclerosis in 1970 to 1999, 68 cases (77ears) were selected for retrospective analysis, which met the criteria of advanced otosclerosis (mixed deafness, with bone-conduction levels exceeding 40 dB and air-conduction levels exceeding 70 dB in 500 - 2000 Hz).

RESULTSThe air-conduction of sixty-eight cases (77 ears) were from 77.32 dB to 53.7 dB (500-2000 Hz) after operation, mean decreased 23.62 dB. Of 71 ears (92.21%) obtained air-conduction improved over 10 dB, of 46 ears (59.74%) gained A-B Gap closure in 10 dB. Air-conduction were from 79.01 dB to 58.23 dB (500 - 4000 Hz) after operation and mean decreased 20.78 dB. Of 68 ears (88.31%) obtained air-conduction improved over 10 dB, of 32 ears (41.56%) gained A-B gap closure in 10 dB. After followed up 5-25 years, of 67 ears were retained stabilization, of 28 ears obtained more improve than postoperation. But 4 ears had drop (all was stapes-elevation and re-improvement after them was reviewed).

CONCLUSIONStapes surgery is effective operation to cured otosclerosis, advanced otosclerosis or far-advanced otosclerosis had greater help to improved hearing.

Adult ; Aged ; Ear Diseases ; surgery ; Female ; Humans ; Male ; Middle Aged ; Otosclerosis ; surgery ; Retrospective Studies ; Stapes Surgery ; methods ; Treatment Outcome

OBJECTIVE：To establish a method for the determination of pyrrotinib concentration in plasma ，and apply it in clinic. METHODS ：After precipitated with methanol ，the plasma sample was determined by LC-MS/MS using imatinib as internal standard. The determination was performed on Ultimate AQ-C 18 column with mobile phase consisted of methanol （containing 0.1％ formic acid ）and water （containing 0.1％ formic acid ）（gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was 40 ℃，and the sample size was 5 µL. The ion source was electrospray ionization source ，and the positive ion scanning was carried out in multiple reaction mode. The ion pairs for quantitative analysis were m/z 583.4→138.3（pyrrotinib）and m/z 494.5→ 393.4（internal standard ），respectively. Thirty breast cancer patients taking pyrrotinib were collected from the Affiliated Hospital of Qingdao University during Jun.-Nov. 2020 to determine their steady-state trough concentrations of pyrrotinib after a week of treatment. RESULTS ：The linear range of pyrrotinib were 5-300 ng/mL（r＝0.999 3）. The lower limit of quantification was 5 ng/mL. RSDs of intra-day and inter-day were not higher than 9.30％，and relative errors （REs）ranged －6.70％-5.04％. REs of stability tests were in the range of －1.92％-5.42％. The extraction method ，matrix effect and residual effect did not affect the quantitative analysis of the substance to be tested. The steady-state trough concentrations of pyrrotinib were 32.6-82.8 ng/mL，with an average plasma concentration of 53.8 ng/mL；there was about 2.54 fold individual difference. CONCLUSIONS ：Established LC-MS/MS method is simple ，sensitive and accurate ，and can be used for the plasma concentration monitoring of pyrrotinib in breast cancer patient.

OBJECTIVETo explore the clinical efficacy of the combined therapy of zinc supplement and Jinye Baidu granule (JBG) on human cytomegalovirus (HCMV) infection.

METHODSOne hundred and forty patients with positive HCMV-IgM were randomly divided into four groups, with 35 cases in each group, that is, the control group (only medicated with JBG), the high-, moderate- and low-dose zinc combined groups (treated with JBG combined with zinc gluconate tablet at dose of 30 mg, 20 mg, 10 mg every day respectively). The negative conversion rate of HCMV-IgM was observed.

RESULTSInsignificant difference in the negative conversion rate was shown in comparison of the control group with the low dose group (P > 0.05), and in comparison of the high dose with the moderate dose group (P > 0.05); however, the rate was significantly lower in the control group than that in the moderate dose and high dose group (P < 0.05).

CONCLUSIONCombined therapy of zinc supplement and JBG can significantly increase the negative conversion rate of HCMV-IgM. The optimal dosage of zinc gluconate tablet was 20 mg once a day.

Adult ; Antibodies, Viral ; blood ; Antiviral Agents ; therapeutic use ; Cytomegalovirus ; drug effects ; Cytomegalovirus Infections ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Immunoglobulin M ; blood ; Phytotherapy ; Zinc ; therapeutic use

INTRODUCTIONThe device closure of atrial septal defects has evolved over the years. In the early days of transcatheter occlusion, balloon sizing was used to choose an appropriate sized device. We postulate that balloon sizing does not value-add to the procedure and is unnecessary.

MATERIALS AND METHODSPatients who had balloon sizing, with (Group 1, n = 38) or without (Group 2, n = 21) atrial septal defect closure, were compared to another group (Group 3, n = 64) who had atrial septal defect closure without balloon sizing. Although the atrial septal defect size (mm) in those without balloon sizing (Group 3) compared to patients who had balloon sizing (Group 1) (18.3 +/- 5.4 vs 14.8 +/- 5.8; P = 0.021) was larger, the Amplatzer septal occluder size chosen (mm) (21.6 +/- 6.3 vs 21.2 +/- 8.1; P = 0.693) was similar.

RESULTSWe analysed the degree of absolute sizing, defined as [(Balloon or Amplatzer occluder size) - (transoesophageal echocardiography size)], versus relative sizing, which is defined as [(Balloon or Amplatzer occluder size)--(transoesophageal echocardiography size) / (Balloon or Amplatzer occluder size)]. It was evident that there was greater absolute and relative over-sizing (6.3 +/- 4.4 mm vs 4.2 +/- 2.1 mm; P = 0.009 and 28.3 +/- 15.4% vs 20.0 +/- 7.0%; P = 0.001, respectively) in patients with balloon sizing (Group 1) compared to those who did not (Group 3). Even a greater degree of absolute (5.1 +/- 3.9 mm vs 9.5 +/- 4.7 mm; P <0.001) and relative over-sizing (24.8 +/- 15.6% vs 33.0 +/- 13.6%; P = 0.001) was observed in patients who had balloon sizing but there was no closure (Group 2) compared to those who had balloon sizing and closure of their defects (Group 1).

CONCLUSIONOur results showed that balloon sizing tended to over-size the atrial septal defect. This may have an important bearing in selecting a larger device than necessary, or even precluding transcatheter closure of the larger atrial septal defects. It is also associated with increased procedural, fluoroscopy time and cost. We suggest that balloon sizing may no longer be necessary in the protocol of device closure of an atrial septal defect.

Adolescent ; Adult ; Aged ; Cardiac Catheterization ; instrumentation ; methods ; Child ; Child, Preschool ; Echocardiography, Transesophageal ; Female ; Heart Septal Defects, Atrial ; diagnostic imaging ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Septal Occluder Device ; Young Adult

INTRODUCTIONBoth gestation and birth weight have significant impact on mortality and morbidity in newborn infants. Nomograms at birth allow classification of infants into small for gestational age (SGA) and large for gestational age (LGA) categories, for risk stratification and more intensive monitoring. To date, the growth charts for preterm newborn infants in Singapore are based on the Fenton growth charts, which are constructed based on combining data from various Western growth cohorts. Hence, we aim to create Singapore nomograms for birth weight, length and head circumference at birth, which would reflect the norms and challenges faced by local infants.

MATERIALS AND METHODSGrowth parameters of all babies born or admitted to our unit from 2001 to 2012 were retrieved. Following exclusion of outliers, nomograms for 3 percentiles of 10th, 50th, and 90th were generated for the gestational age (GA) ranges of 25 to 42 weeks using quantile regression (QR) combined with the use of restricted cubic splines. Various polynomial models (second to third degrees) were investigated for suitability of fit. The optimum QR model was found to be a third degree polynomial with a single knotted cubic spline in the mid-point of the GA range, at 33.5 weeks. Check for goodness of fit was done by visual inspection first. Next, check was performed to ensure the correct proportion: 10% of all cases fall above the upper 90th percentile and 10% fall below the lower 10th percentile. Furthermore, an alternative formula-based method of nomogram construction, using mean, standard deviation (SD) and assumption of normality at each gestational age, was used for counterchecking.

RESULTSA total of 13,403 newborns were included in the analysis. The new infant-foetal growth charts with respect to birth weight, heel-crown length and occipitofrontal circumference from 25 to 42 weeks gestations with the 10th, 50th and 90th were presented.

CONCLUSIONNomograms for birth weight, length and head circumference at birth had significant impact on neonatal practice and validation of the Singapore birth nomograms against Fenton growth charts showed better sensitivity and comparable specificity, positive and negative predictive values.

Birth Weight ; Body Height ; Cephalometry ; Child ; Cohort Studies ; Female ; Gestational Age ; Growth Charts ; Humans ; Infant, Newborn ; Male ; Nomograms ; Reference Values ; Singapore