Clinical effect and safety of sofosbuvir-based regimens in treatment of hepatitis C virus-associated glomerulonephritis / 临床肝胆病杂志

ObjectiveTo investigate the clinical effect and safety of sofosbuvir-based regimens in the treatment of hepatitis C virus (HCV)-associated glomerulonephritis (HCV-GN). MethodsA retrospective analysis was performed for the clinical data of 5 patients with HCV-GN who were given sofosbuvir-based antiviral therapy in The Second Affiliated Hospital of Xi’an Jiaotong University from April 2015 to October 2018, and their clinical outcome and safety were analyzed. The patients were evaluated in terms of sustained virologic response at 12 weeks after treatment ended (SVR12), changes in liver/renal function and urinary protein during and after treatment, and safety. ResultsFive patients were enrolled, with an age of 27-81 years. There were 4 male patients, among whom 2 had liver cirrhosis. Of all patients, 4 had genotype 1b and 1 had genotype 2a. Renal biopsy was performed for 2 patients, who were diagnosed with membranoproliferative glomerulonephritis and mesangial proliferative glomerulonephritis, respectively. Of all patients, 2 received sofosbuvir+ribavirin, 2 received ledipasvir/sofosbuvir, and 1 received sofosbuvir/velpatasvir for 12 or 24 weeks. All 5 patients achieved SVR12. There were significant reductions in alanine aminotransferase and 24-hour urinary protein excretion from baseline to the end of treatment and 12 weeks of follow-up, with a slight increase in serum albumin. Blood urea nitrogen and serum creatinine were improved or showed no change. Only 1 patient experienced adverse gastrointestinal events associated with ribavirin. ConclusionSofosbuvir-based regimens have good clinical effect and tolerability in patients with HCV-GN. Long-term follow-up should be performed to evaluate the long-term prognosis of renal disease after HCV clearance.

Expression of ghrelin and its receptor GHS-R in the hypothalamus and gastrointestinal tract in rats with chronic renal failure / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of ghrelin and its receptor, growth hormone secretagogue receptor (GHS-R), in the hypothalamus and gastrointestinal tract in rats with chronic renal failure (CRF) and explore their relationship with the disorder of gastrointestinal tract motility.</p><p><b>METHODS</b>SD rats were randomly divided into sham-operated group (n=8) and CRF group (n=16), and in the latter group, the rats were subjected to 5/6 nephrectomy to induce CRF. Real-time PCR and immunohistochemical staining were used to detect the distribution of mRNA and protein of ghrelin and GHS-R in the gastric fundus, duodenum, and hypothalamus.</p><p><b>RESULTS</b>The rats in the CRF group showed a significantly higher expression of ghrelin mRNA and protein in the gastric fundus but a lower expression in the hypothalamus than those in the sham-operated group (P<0.01), but the expression in the duodenum was similar between the two groups (P>0.05). The expression of GHS-R mRNA and protein in the gastric fundus was significantly higher in the CRF group than in the sham-operated group (P<0.01), while in the hypothalamus and duodenum, the expression was significantly lower in the CRF group (P<0.01).</p><p><b>CONCLUSION</b>The different distribution patterns of ghrelin and GHS-R in the tissues may be an important pathological basis of gastrointestinal motility disorder in CRF.</p>

EMMPRIN mediates matrix metalloproteinase 9 expression and monocyte migration: evidence from EMMPRIN knockdown by RNA interference / 中国病理生理杂志

AIM: Although the evidence indicates that extracellular matrix metalloproteinase inducer (EMMPRIN) is closely associated with matrix metalloproteinase (MMP) expression in tumor cells, tumor invasion and metastasis, no direct proof that EMMPRIN regulates MMPs in monocytes, especially in the atherogenic milieu is observed. Here we tested this hypothesis by examining MMP-9 expression in macrophages/foam cells and monocyte migration through EMMPRIN knockdown by siRNA. METHODS: The methods of qPCR and Western blotting were used to detect the suppressions of EMMPRIN mRNA and protein expression in macrophages and foam cells transfected with EMMPRIN-specific siRNA. The protein expression of MMP-9 in macrophages and foam cells was also determined. Monocyte migration after EMMPRIN knockdown was observed by a Transwell assay. RESULTS: EMMPRIN knockdown by siRNA markedly abolished the MMP-9 expression by 50% and 40% in macrophages and foam cells, respectively. Migration induced by chemotactic factor MCP-1 and VEGF was significantly attenuated (P<0.05) in monocytes treated with EMMPRIN-siRNA. CONCLUSION: The protein expression and secretion of MMP-9 are down-regulated by EMMPRIN knockdown during monocyte differentiation into macrophages and foam cells. Moreover, EMMPRIN siRNA treatment also prevents monocyte migration. Thus, EMMPRIN plays a key regulatory role for MMP activity and monocyte migration, making it a potential target for pharmacological intervention of atherosclerosis.

Role of renal sympathetic nerves in renal sodium transport in ouabain-hypertensive rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of renal sympathetic nerves in renal sodium transport in ouabain-hypertensive rats (OHR).</p><p><b>METHODS</b>Sixteen male SD rats with sham renal denervation (Sham-RDNX) and 16 with renal denervation (RDNX) were randomly into normal control group and ouabain group to receive intraperitoneal injection of normal saline (1 ml/kg) and ouabain (27.8 µg/kg) once a day, respectively. Systolic blood pressure (SBP), heart rate and body weight were recorded weekly. Food consumption of the rats was determined twice a week. After a 4-week treatment, blood and 24 h urine samples were collected to measure the serum and urinary concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the postproximal tubules (FDRNa) were calculated. Plasma renin activity was determined by radioimmunoassay. Norepinephrine was extracted from the renal tissue and assayed for norepinephrine content by HPLC.</p><p><b>RESULTS</b>The body weight, food intake and heart rate showed no significant difference among the 4 groups (P > 0.05). After 4 weeks, the SBP of control RDNX group (CDNX) was significantly lower than that of the control Sham-DNX group (Csham)(P < 0.05); the SBP of ouabain RDNX group (ODNX) was also significantly lower than that of ouabain Sham-DNX group (Osham) (P < 0.05); RNDX lowered SBP by about 10 mmHg in both ouabain groups and control groups. The SBP was significantly higher in Osham and ODNX groups than in the corresponding control groups (P < 0.01), also significantly higher in ODNX group than in Csham group (P < 0.01). Ccr showed no significant difference among the 4 groups(P > 0.05). FENa, FELi and FDRNa were significantly lower in ouabain groups than in the corresponding control groups (P < 0.05, P < 0.01, P < 0.05), but FENa, FELi and FDRNa of ODNX group were similar with those of Osham group (P > 0.05); FENa , FELi and FDRNa were similar between CDNX and Csham groups (P > 0.05). The plasma renin activity was comparable between the 4 groups (P > 0.05). Renal norepinephrine level was markedly reduced in RDNX group compared with that in Sham-RDNX group in both ouabain and control groups (P < 0.01).</p><p><b>CONCLUSION</b>The increase of proximal tubule sodium reabsorption in OHR is not dependent on the renal sympathetic nerve.</p>

The effect of Levocarnitine on nutritional status and lipid metabolism during long-term maintenance hemodialysis / 药物分析学报

Objective To investigate the effect of Levocarnitine on lipid metabolism and nutritional status of maintenance hemodialysis (MHD) patients and possible mechanism. Methods A total of 40 MHD patients [mean age (53.5±7.1) years] who underwent normal hemodialysis more than 6 months were randomly classified into two groups, Levocarnitine supplemented group (LS-G) (n=20; Levocarnitine supplementation after each normal hemodialysis session, at a dose of 1.0 g/day by intravenous administration) and control group (C-G) (n=20; normal hemodialysis). Before treatment, one month and three months after treatment we respectively measured or observed the following items, the tolerance to hemodialysis, carnitine level in plasma, C-reactive protein, IL-6, TNF-α, percentage of neutrophil, and some relevant nutritional parameters, such as lipid profile, transferrin, total protein, albumin and prealbumin levels. Comparative analysis was conducted between the two groups. Results In LS-G three months after treatment, the levels of carnitine, hemoglobin, and prealbumin in plasma were significantly increased (P<0.05), but C-reactive protein, neutrophil percentage, low-density lipoprotein and triglyceride were significantly decreased (P<0.05) in contrast to those in C-G and before treatment. Transferrin, total protein, and albumin were elevated in LS-G, with no statistical significance. Conclusion There was a significant improvement of lipid metabolism and nutritional status for the long-term maintenance hemodialysis patients with Levocarnitine supplementation. And this improvement is related to the decrease of inflammatory factors.

Comparison between anti-ouabain egg yolk(IgY) and rabbit antibody(IgG) in enzyme-linked immunosorbent assay / 中国应用生理学杂志

<p><b>AIM</b>To improve specificity and accuracy of endogenous ouabain measurement assay.</p><p><b>METHODS</b>Anti-ouabain polyclonal antibody egg yolk (IgY) and anti-ouabain rabbit antibody (IgG) were prepared respectively. In the presence of two kinds of antibody, then the specificity and accuracy of enzyme-linked immunosorbent assay (ELISA) were compared.</p><p><b>RESULTS</b>The ELISA, in the presence of IgY, provided a sensitivity of the average intraassay coefficient of variation(CV) was 2.03%, and the inter-assay CV was 2.34% respectively. In contrast, IgG were 2.83% and 3.29%. No significant interferences were observed with hydrocortisone and dexamethasone. There was 3.45% vs. 5.95%, 3.20% vs. 5.20% of crossreaction with cedilanid and digoxin.</p><p><b>CONCLUSION</b>The specificity and accuracy of ELISA, in which IgY was used, were more better than IgG.</p>

Changes in renal sodium transport during hypertension development in ouabain-hypertensive rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes in renal sodium transport during development of hypertension in ouabain-hypertensive rats (OHR) and further elucidate the role of ouabain in the pathogenesis of hypertension.</p><p><b>METHODS</b>Eighty male SD rats weighing 80-100 g were randomized equally into normal control and ouabain groups and treated with intraperitoneal injection of normal saline (1 ml/kg) and ouabain (27.8 microg/kg) once daily, respectively. Systolic blood pressure (SBP) and body weight of the rats were recorded weekly. One week before sacrifice scheduled at weeks 2, 4, 6 and 8, respectively, the rats were individually housed in metabolic cages to determine food consumption twice. Blood and 24-hour urine samples were collected to measure serum and urine concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the distal tubules (FDRNa) were calculated.</p><p><b>RESULTS</b>The body weight and food intake between ouabain groups and control groups were comparable during the experiment (P>0.05). Blood pressure was also comparable in the two groups after 2 weeks (P>0.05). At week 4, however, blood pressure of ouabain group was significantly higher than that of the control group (P<0.001) and increased in a dose-dependent manner. The SBP in ouabain group appeared to reach a plateau at week 7. Ccr and plasma sodium (PNa) were similar in the 2 groups during the experiment (P>0.05). FELi was significantly lower at weeks 2, 4 and 6 in ouabain group than in the control group (P<0.01), and FELi decrement in ouabain group was accompanied by reduced sodium excretion. FENa was significantly lower at week 4 in ouabain group than in the control group (P<0.05), but this difference was not significant in weeks 2 and 6 (P>0.05). At weeks 2, 4 and 6, ouabain group showed significantly lower FDRNa than the control group (P<0.05), suggesting the compensation of the distal nephron segments. After 8 weeks, FENa, FELi and FDRNa were similar between the two groups (P>0.05).</p><p><b>CONCLUSIONS</b>Ouabain can increase renal proximal tubule reabsorption of sodium and consequently decrease renal sodium excretion in OHR, which can contribute to alteration of the pressure-natriuresis relationship in OHR, and play an important role in the development and maintenance of hypertension of OHR.</p>

Resveratrol inhibits expression of EMMPRIN from macrophages / 药学学报

<p><b>AIM</b>To investigate the effect of resveratrol on EMMPRIN expression of macrophages.</p><p><b>METHODS</b>Human monocytic cell line THP-1 cells were co-cultured with EMMPRIN-highly-expressed MCF-7 cells; MMP-9 production was assayed by zymography. THP-1 cells were induced by PMA, expression of EMMPRIN was assayed by Western blotting. Cells were treated with resveratrol or PPARgamma agonist--pioglitazone during differentiation, EMMPRIN expression and MMP-9 activity were assayed. U937 cells were co-transfected with PPARy expression and luciferase-coding reporter vector, then cultured with pioglitazone or resveratrol, the activating capability of resveratrol on PPARgamma was evaluated by measuring the luciferase activity. THP-1 cells were pretreated with PPARgamma antagonist--GW9662 before pioglitazone or resveratrol treatment, then assayed for EMMPRIN expression and MMP-9 production.</p><p><b>RESULTS</b>EMMPRIN expression was greatly increased during the differentiation from monocytes to macrophages; co-culturing with MCF-7 cells significantly increased MMP-9 production by monocytes. Both resveratrol and pioglitazone markedly inhibited EMMPRIN expression during monocytes differentiation. Resveratrol significantly activated PPARgamma and GW9662 greatly decreased the effect of resveratrol on EMMPRIN and MMP-9.</p><p><b>CONCLUSION</b>EMMPRIN expression is greatly up-regulated from monocytes to macrophages, which may play a role in inducing MMPs production by monocytes/macrophages. Resveratrol can significantly inhibit EMMPRIN expression via activating PPARgamma, which may be the underlying mechanism of its inhibitory effect on MMPs production by monocytes/macrophages.</p>

Renal sodium handling in ouabain-hypertensive rats / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate renal sodium handling of ouabain-hypertensive rats and the role of renal sodium handling in pathogenesis of hypertension using endogenous trace lithium as a marker of proximal sodium reabsorption.</p><p><b>METHODS</b>Forty male Sprague-Dawley (SD) rats weighting 180-220 g were equally divided into normal control group and ouabain group randomly. Rats were infused with normal saline 1 ml/ (kg x d) or ouabain 27.8 microg/ (kg-d) intraperitoneally once a day respectively. Systolic blood pressure (SBP) and body weight were recorded weekly. Rats were sacrificed after 2 and 6 weeks respectively. Blood and 24 hour urine sample were collected to measure the serum and urinary concentration of sodium, potassium, trace lithium, and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FE(Na)), and fractional excretions of lithium (FE(Li)), the ratios of urinary lithium to sodium (U(Li)/U(Na)), the ratios of urinary potassium to sodium (U(K)/U(Na)), and fractional reabsorption of sodium in the postproximal tubules (FDR(Na)) were also calculated. All were studied on their normal diet and ate salt freely.</p><p><b>RESULTS</b>Blood pressure had no significant difference in these two groups after 2 weeks (P > 0.05); After 4 weeks, however, blood pressure was significantly higher in ouabain group than in control group (P < 0.01). Body weight of rats had no significant difference during the experiment period (P > 0.05). Ccr and FE(Na) were similar in these 2 groups (P > 0.05). FE(Li), U(Li)/U(Na), U(K)/U(Na), and FDR(Na) of ouabain group were significantly lower than control group after 2 and 6 weeks (P < 0.05, P < 0.01, P < 0.001 respectively).</p><p><b>CONCLUSION</b>The reabsorption of sodium increases in the proximal tubule in ouabain-hypertensive rats, and such increase occurs before the development of hypertension. Therefore, increase of proximal reabsorption of sodium may be involved in the pathogenesis of ouabain-induced hypertension.</p>

Neuropsychiatric symptoms in dementia and elderly people in the community: results from the Beijing Dementia Cooperative Study / 中华流行病学杂志

<p><b>OBJECTIVE</b>To determine the prevalence of neuropsychiatric symptoms in dementia and normal elderly people living in the Chinese community of Beijing.</p><p><b>METHODS</b>A cross-sectional study derived from the Beijing Dementia Cooperative Study was carried out a population survey was carried out on a total of 1540 participants aged 65 years and older living in Beijing city and rural areas. All the individuals and 373 demented elderly people completed a series of neuropsychological examination and the Neuropsychiatric Inventory (NPI).</p><p><b>RESULTS</b>Among the dementia participants, 49.33% had exhibited neuropsychiatric symptoms (35.66% rated as clinically significant), in which 80.4% reported 2 or more disturbances, with depression (23.86%), apathy (21.72%) and anxiety (20.38%) being most common. Of the 1540 normal individuals, 18.25% of them exhibited neuropsychiatric symptoms (6.49% rated as clinically significant), in which 53% reported 2 or more disturbances, with sleepless (10%), depression (8.9%) and anxiety (6.97%) being the most common.</p><p><b>CONCLUSION</b>To our knowledge, this was the first multi-center study on neuropsychiatric disturbances in dementia and cognitive normal elderly people. Neuropsychiatric symptoms occurred mainly in persons with dementia and of clinical severity. Though the neuropsychiatric disturbances reported in cognitive normal individuals were lower and less serious compared to dementia, they should not be neglected. These finding suggested that a screening programme focusing on identifying these symptoms should be included in the physician's diagnostic tools for dementia.</p>

Effect of PPAR ligands on extracellular matrix metalloproteinase inducer expression in macrophages and foam cells / 中国病理生理杂志

AIM: To investigate the role of PPAR ? or ? ligands in regulating the expression of extracellular matrix metalloproteinase inducer(EMMPRIN).METHODS: THP-1 monocytes were induced into macrophages and foam cells in vitro then interfered with clofibrate and pioglitazone.The cells and supernatant were collected after 24 h,respectively.EMMPRIN gene and its protein were assessed by real-time PCR and Western blotting in different interferences.The concentration of matrix metalloproteinases(MMP-9) was measured with ELISA method and the activity of MMP-9 was detected with gelatin zymography.RESULTS: Two known PPAR ? or ? ligands,colfibrate and pioglitzaone,were found,both of which inhibited EMMPRIN expression in macrophages and foam cells.The inhibition was correspondent to the secretion and activity of MMP-9 simultaneously.CONCLUSION: Both PPAR ? and ? ligands inhibit EMMPRIN expression,which may account for their effect on inhibition of MMPs.