BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

This study aimed to investigate the effect of methyl eugenol(ME) on hypoxia/reoxygenation(H/R)-induced injury of human renal tubular epithelial HK-2 cells and its mechanism. The viability of HK-2 cells cultured with different concentrations of ME and exposed to H/R was detected by cell counting kit-8(CCK-8) assay. The effect of ME on the morphology of HK-2 cells was observed under an inverted microscope. The content of intracellular reactive oxygen species in different groups was detected after 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA) fluorescence staining. Cell apoptosis was determined by flow cytometry. Changes in mitochondrial membrane potential were monitored by JC-1 dye. The concentrations of nuclear factor erythroid 2 related factor 2(Nrf2), heme oxygenase-1(HO-1), and nicotinamide adenine dinucleotide phosphatase oxidase 4(Nox4) were measured by Western blot, followed by the assay of Nrf2 concentration changes in cytoplasm and nucleus by confocal fluorescence staining. The results showed that when the concentration of ME was 0-40 μmol·L~(-1), the activity of HK-2 cells was not affected. Compared with the model group, ME enhanced the activity of HK-2 cells and the cell morphology was normal. As revealed by further experiments, ME inhibited the release of reactive oxygen species and the decline in mitochondrial membrane potential of HK-2 cells after H/R injury, promoted Nrf2/HO-1 expression and Nrf2 translocation to the nucleus, and down-regulated the expression of Nox4, thereby significantly reducing apoptosis. This protective effect of ME could be reversed by the specific Nrf2 inhibitor ML385. These findings have preliminarily proved that ME effectively protected HK-2 cells against H/R injury, which might be related to its promotion of Nrf2/HO-1 signaling pathway and inhibition of Nox4. Such exploration on the possible mechanism of ME in the treatment of renal ischemia-reperfusion injury(IRI) and protection of organ function from the perspective of antioxidant stress has provided reference for related research on the treatment of acute kidney injury with traditional Chinese medicine.
Apoptosis ; Epithelial Cells/metabolism* ; Eugenol/pharmacology* ; Heme Oxygenase-1/metabolism* ; Humans ; Hypoxia ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Reactive Oxygen Species ; Reperfusion Injury/drug therapy*

Objective To investigate the effects of downregulated pregnane X receptor (PXR)on expression and activity of P-glycoprotein(P-gp)in mouse brain microvascular endothelial cells (mBMEC)exposed to glutamate (GLU)to mimic conditions during seizures. Methods The bEnd.3 cells,were cultured in vitro and treated with culture medium containing 0 μmol,10 μmol,50 μmol,100 μmol GLU for 30 min and exposed to 100 μM GLU for different durations (0 min,15 min,30 min). With PXR knockdown using siRNA,the cells were divided into NC siRNA plus GLU group and siRNA-PXR plus GLU group. Western blotting was used to detect the protein expressions of P-gp and PXR in each group. Immunofluorescence assay was used to detect localization of PXR in cells. The expression of P-gp mRNA was detected by RT-qPCR. Rhodamine123 (Rh123)accumulation assay was used to study the activity of the P-gp in cells.Results PXR and P-gp protein expressions in the 50 μmol and 100 μmol GLU group were significantly higher than that in the blank group(P＜0.05),especially maximal expressions occurred in the 100 μmol GLU group. GLU exposures as short as 15 min and 30 min significantly increased PXR expressions(all P＜0.05);P-gp expression in the 30 min groups was higher than that in the blank group (P＜0.05 ). The data of immunofluorescence analysis suggested that the PXR nuclear accumulation increased in the 100 μM GLU group, compared with the blank group(P＜0.05). Compared with NC siRNA plus GLU group,the protein level of PXR was decreased by approximately 37%[(1.00 ± 0.00)vs(0.63 ± 0.18);t＝3.41,P＝0.02]and the levels of P-gp protein and mRNA were respectively decreased by 43%[(1.00 ± 0.00)vs (0.57 ± 0.09);t＝7.94,P＝0.00] and 52%[(1.00 ± 0.04)vs (0.48 ± 0.08);t ＝10.98,P＝0.00]in the siRNA-PXR plus GLU group. The fluorescence intensity of intracellular Rh123 in the GLU group (0.72 ± 0.01)was lower than that in the blank group [(1.00 ± 0.03);t ＝9.66,P＝0.00]. The fluorescence intensity of Rh123 in the GLU plus verapamil (P-gp inhibitor)group (1.07 ± 0.04)was higher than that in the GLU group (t＝ －11.93,P＝0.00). The fluorescence intensity of Rh123 in the siRNA-PXR plus GLU group (0.91 ± 0.03)was higher than that in the NC siRNA plus GLU group[(0.69 ± 0.05);t＝ －7.52,P＝0.00]. Conclusions Downregulation of PXR expression results in the inhibition of P-gp expression and activity in the mBMEC exposed to GLU to mimic seizures. PXR may play an important role in the regulation of seizure-induced expression and activity of P-gp in the blood-brain barrier.

Objective To investigate the effect of family factors on the prognosis of patients with epilepsy and the relationship between family factors and clinical characteristics of epilepsy.Methods Data were collected from 107 patients definitely diagnosed with epilepsy who were treated by antiepileptic drugs for at least two years.All the patients were divided into good or poor prognosis group according to whether achieving at least one year free of seizures.The clinical and family data were colleeted.The questionnaire Family Adaptability and Cohesion Evaluation Scale-Ⅱ-Chinese Version containing 30 items was used for patients and the Epilepsy Knowledge Questionnaire containing 34 questions for primary caregiver.We compared the clinical and family factors between the two groups to identify the predictors of poor control of seizures with univariate and multiple Logistic regression,and observed the relationship between family factors and clinical features such as course,type of seizure,seizure frequency,etc,with Pearson correlation analysis.Results Patients with poor prognosis were more likely to have interictal epileptiform discharges (IEDs),multidrug treatment and pre-treatment seizure frequency of more than once monthly (84.6％ (44/52) vs 50.9 ％ (28/55),x2 =13.797,P =0.000;63.5 ％ (33/52) vs 34.5 ％ (19/55),x2 =8.947,P =0.003;38.5％ (20/52) vs 5.5％ (3/55),x2 =17.257,P =0.000).Family in rural area,unbalanced family type,number of family members were much more in poor prognosis group than in good prognosis group (51.9％ (27/52) vs 25.5 ％ (14/55),x2 =7.923,P =0.005;80.8 ％ (42/52) vs 49.1％ (27/55),x2 =11.712,P=0.000;4.1 ± 1.1 vs 3.6 ±0.8,t=2.631,P=0.010).And average family income,education level of father,the level of epilepsy knowledge of primary caregiver were significantly lower in poor prognosis group than in good prognosis group (19/20/13 vs 11/17/27,x2 =7.198,P =0.027;15/30/7 vs 4/34/17,x2 =10.709,P =0.005;36/11/5 vs 15/25/15,x2 =19.022,P =0.000).Multiple Logistic regression analysis demonstrated that IEDs (OR =12.332,95％ CI 2.756-55.190,P =0.001),pretreatment seizure frequency of more than once monthly (OR =8.401,95％ CI 1.573-44.884,P =0.013)were clinical risk factors of unfavorable prognosis;more family members (OR =3.021,95％ CI 1.554-5.870,P =0.001),poor epilepsy knowledge of primary caregiver (OR =3.392,95％ CI 1.304-8.821,P=0.012) and unbalanced family type (OR=4.794,95％ CI 1.217-18.894,P=0.025) were independent family risk factors of poor prognosis.The level of epilepsy knowledge of primary caregiver was inversely associated with duration (r =-0.237,P =0.014).Conclusions The prognosis of epilepsy is not only affected by clinical factors,but also by family factors.More family members,poor epilepsy knowledge of primary caregiver and unbalanced family type are independent risk factors of unfavorable prognosis.The poorer epilepsy knowledge the primary caregivers have,the longer duration the disease has.

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and site-specific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the −2000 to −1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the −1997 to −1700 and −1091 to −811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.
Binding Sites ; Cholesterol ; Chromatin Immunoprecipitation ; Computational Biology ; Coronary Artery Disease ; Foam Cells* ; Humans ; Interleukin-10* ; Interleukin-33* ; Luciferases ; Macrophages* ; Mutagenesis, Site-Directed ; Phosphorylation ; RNA, Messenger ; Transcription Initiation Site

Objective To investigate precipitants of epileptic seizure, and to explore the correlation between various precipitants and relationship between precipitants and clinical features of epilepsy.Methods Data were collected from 154 patients attending a tertiary-care epilepsy clinic of Nanjing Brain Hospital between April 2015 and April 2016.The patients with epilepsy were older than 16 years, had a clinical history of one year or more, and one seizure at least a year and one seizure at least in the latest three months.An enclosed questionnaire was combined with open interview to identify and characterize seizure precipitants and clinical characteristics of patients.Patients were asked respectively whether there were some precipitants three months before and during last three months.Correlation between seizure precipitants and relationship between precipitants and clinical characteristics, such as age, gender, course, seizure frequency and so on, were calculated.Results A total of 125 (81.2%) participants reported at least one precipitant.Common precipitants (in descending order) were as follows: emotional stress (56.0%), sleep disorder (38.4%), fatigue (27.2%), missed medication (20.0%).There were one to six different precipitants for one patient, and 60.8% of patients had two or more precipitants.There was a correlation between emotional stress and sleep disorders as well as fatigue (χ2=4.665, 8.668;P<0.05).Patients with idiopathic epilepsy were more sensitive to sleep disorders.There was no relationship between total precipitants and clinical features such as age, gender, age of onset, duration, type of seizure, seizure frequency, number of drug taking and so on.Conclusions Seizure precipitants were found widespread.The most common precipitants were found to be emotional stress, sleep disorders, fatigue and missed medication.There existed a correlation between emotional stress and sleep disorders as well as fatigue.There was no connection between total precipitants and patient′s demographic characteristics as well as clinical features.However, the type of seizure precipitants was different in patients with different demographic and clinical characteristics.

HIV/STIs remain a major global public health problem. One of the global strategies for the prevention and control of HIV/STIs is to interrupt their transmission, which requires the public health methods based on scientific evidence and cost-effectiveness. The scale-up of male circumcision services in the priority countries of the HIV-prevention project in sub-Saharan Africa has been hampered by the scarcity of trained providers and relative technical difficulty of male circumcision techniques recommended by WHO and UNAIDS. Shang Ring is an innovative and disposable device for male circumcision, which has been safely used for over 600 000 males in China since 2006. Clinical studies of more than 3 000 cases of Shang Ring circumcision in China, Kenya, Zambia, and Uganda have demonstrated its safety, effectiveness, acceptability and ease of use. The most obvious advantages of Shang Ring include short procedure time (3-6 min), excellent postoperative cosmesis, low rate of complications, high acceptance by clients and providers, ease of use, and standardization for reliable performance. As an innovative technique, Shang Ring has a great potential for facilitating the safe and effective scale-up of circumcision services. This article comprehensively reviews the clinical studies of Shang Ring male circumcision in China and Africa.
Africa ; China ; Circumcision, Male ; instrumentation ; methods ; HIV Infections ; prevention & control ; Humans ; Male

Increasingly accumulated results from randomized controlled trials and other clinical studies have demonstrated that male circumcision reduces the risks of acquisition and transmission of HIV, HPV, HSV-2, and other sexually transmitted infections, and thus has a potential role in preventing cervical cancer, penile cancer and prostate cancer. The prevalence of male circumcision in China is currently less than 5%. The clinical evaluation studies and randomized controlled trials of the Shang Ring device showed excellent safety profiles, extremely high acceptability, and satisfaction among the participants and service providers in Africa and China. Given the recent recommendations by the World Health Organization and the Joint United Nations Program on HIV/AIDS (UNAIDS), voluntary medical male circumcision should be promoted in China at the national level as an important alternative intervention to reduce reproductive tract infections and prevent both males and females from reproductive tract cancers. More emphasis is required on the studies of the long-term health benefits of male circumcision in uro-andrology.
China ; Circumcision, Male ; Female ; HIV Infections ; prevention & control ; Humans ; Male ; Penile Neoplasms ; prevention & control ; Prevalence ; Randomized Controlled Trials as Topic ; Sexually Transmitted Diseases ; prevention & control ; Urinary Tract Infections ; prevention & control ; Uterine Cervical Neoplasms ; prevention & control ; World Health Organization

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

OBJECTIVETo identify the clinical and pathological features of acute myeloid leukemia with B lymphoproliferative disorders.

METHODSThe characteristics of 3 cases of acute monocytic leukemia with untreated chronic lymphocytic leukemia/monoclonal B-cell lymphocytosis were reported with literatures review.

RESULTSThe patients presented with a history of anemia, bleeding and/or fever. Acute monocytic leukemia was diagnosed by bone marrow morphology, cytochemistry and pathology studies. Immunophenotyping by flow cytometry analysis showed a significant population of absolute B-lymphocyte count of > 5×10(9)/L in a patients, similar to that of chronic lymphocytic leukemia.

CONCLUSIONSThe association of acute monocytic leukemia and untreated chronic lymphocytic leukemia/monoclonal B-cell lymphocytosis was a rare event. The abnormal B lymphocytes was likely to be misdiagnosis. Thus, it was important to combine several kinds of laboratory studies, especially flow cytometry to identify this rare disorder.

Aged ; B-Lymphocytes ; pathology ; Female ; Humans ; Leukemia, Monocytic, Acute ; complications ; diagnosis ; pathology ; Lymphocytosis ; complications ; diagnosis ; pathology ; Middle Aged