Autosomal dominant polycystic kidney disease （ADPKD）, the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal repl...Autosomal dominant polycystic kidney disease （ADPKD）, the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal replacement therapy, is a systemic disorder mainly involving the kidney but cysts can also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Though computed tomography and magnetic resonance imaging （MRI） were similar in evaluating 81% of cystic lesions of the kidney, MRI may depict septa, wall thickening or enhancement leading to upgrade in cyst classification that can affect management. A screening strategy for intracranial aneurysms would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD and reduce the fnancial impact on society of the disease. Current treatment strategies include reducing： cyclic adenosine monophosphate levels, cell proliferation and fluid secretion. Several randomised clinical trials （RCT） including mammalian target of rapamycin inhibitors, somatostatin analoguesand a vasopressin V2 receptor antagonist have beenperformed to study the effect of diverse drugs ongrowth of renal and hepatic cysts, and on deteriorationof renal function. Prophylactic native nephrectomy isindicated in patients with a history of cyst infection orecurrent haemorrhage or to those in whom space musbe made to implant the graft. The absence of largeRCT on various aspects of the disease and its treatmen leaves considerable uncertainty and ambiguity in many aspects of ADPKD patient care as it relates to end stage renal disease （ESRD）. The outlook of patients with ADPKD is improving and is in fact much better than that for patients in ESRD due to other causes. This review highlights the need for well-structured RCTs as a frst step towards trying newer interventions so as to develop updated clinical management guidelines.展开更多
AIM： To determine the temporal expression and pattern of Rel/nuclear factor （NF）-κB proteins in renal tissue in polycystic kidney disease （PKD）. METHODS： The renal expression of Rel/NF-κB proteins was determin...AIM： To determine the temporal expression and pattern of Rel/nuclear factor （NF）-κB proteins in renal tissue in polycystic kidney disease （PKD）. METHODS： The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofuorescence and immunoblot analysis in Lewis polycystic kidney rats （LPK, a genetic ortholog of human nephronopthsis-9） from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes （TNFa and CCL2） were determined. NF-κB was also histologically assessed in human PKD tissue.RESULTS： Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation （peaking at weeks 3 and 10 respectively）, and progressive interstitial fibrosis （with a smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards）. Rel/NF-κB proteins （phosphorylated-p105, p65, p50, c-Rel and RelB） were expressed in cystic epithelial cells （CECs） of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBa protein levels, and TNFa and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identifed in the CECs of LPK and human polycystic kidneys. CONCLUSION： Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases.展开更多
Objective： To compare the efficacy of acupoint embedding combined with clomiphene with clomiphene alone in the treatment of patients with polycystic ovary syndrome （PCOS）. Methods： Sixty patients who met the diag...Objective： To compare the efficacy of acupoint embedding combined with clomiphene with clomiphene alone in the treatment of patients with polycystic ovary syndrome （PCOS）. Methods： Sixty patients who met the diagnostic criteria of PCOS were randomly divided into the acupuncture-medicine combination （30 cases） and the single medicine （30 cases） groups. For a total of 4 menstrual cycles, patients in the acupuncture-medicine combination group were treated with acupoint embedding combined with oral clomiphene, whereas those in the single medicine group were treated with clomiphene only. Clinical efficacy of the two treatments was observed after 2 months of treatment, and body mass index （BMI）, number of menstrual cycles, luteinizing hormone （LH）, follicle stimulating hormone （FSH）, LH / FSH ratio, and serological levels of testosterone before and after treatment were analyzed. Results： Compared with the single medicine group, patients in the acupuncture-medicine group showed lower BMI （24.3 ± 1.6 vs 26.1 ± 1.8） and higher number of menstrual cycles （3.6 ± 1.5 vs 2.8 ± 1.2）; the differences were statistically significant （P = 0.018, P = 0.025）. LH （9.53 ± 5.46 vs 12.29 ± 5.67） and LH / FSH （1.02 ± 0.57 vs 1.45 ± 0.23） levels were significantly decreased （P = 0.041, P = 0.039）. Compared to before treatment, BMI （24.3 ± 1.6 vs 27.6 ± 1.4） was lower and the number of menstrual cycles was higher （3.6 ± 1.5 vs 1.8 ± 0.8） after treatment; the differences were statistically significant （P = 0.034, P = 0.024）. The levels of LH （9.53 ± 5.46 vs 18.12 ± 11.04） and LH / FSH （1.02 ± 0.57 vs 2.38 ± 1.09） were significantly decreased （P = 0.007 P = 0.005）. Total effective rates were 76.67% and 70% in the acupuncture-medicine combination and single medicine groups, respectively; the difference between the two groups was statistically significant （P = 0.043）. Conclusion： Acupoint embedding combined with clomiphene in the treatment of PCOS could downregulate BMI, LH, and LH / FSH ratio, and increase the number of menstrual cycles.展开更多
文摘Autosomal dominant polycystic kidney disease （ADPKD）, the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal replacement therapy, is a systemic disorder mainly involving the kidney but cysts can also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Though computed tomography and magnetic resonance imaging （MRI） were similar in evaluating 81% of cystic lesions of the kidney, MRI may depict septa, wall thickening or enhancement leading to upgrade in cyst classification that can affect management. A screening strategy for intracranial aneurysms would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD and reduce the fnancial impact on society of the disease. Current treatment strategies include reducing： cyclic adenosine monophosphate levels, cell proliferation and fluid secretion. Several randomised clinical trials （RCT） including mammalian target of rapamycin inhibitors, somatostatin analoguesand a vasopressin V2 receptor antagonist have beenperformed to study the effect of diverse drugs ongrowth of renal and hepatic cysts, and on deteriorationof renal function. Prophylactic native nephrectomy isindicated in patients with a history of cyst infection orecurrent haemorrhage or to those in whom space musbe made to implant the graft. The absence of largeRCT on various aspects of the disease and its treatmen leaves considerable uncertainty and ambiguity in many aspects of ADPKD patient care as it relates to end stage renal disease （ESRD）. The outlook of patients with ADPKD is improving and is in fact much better than that for patients in ESRD due to other causes. This review highlights the need for well-structured RCTs as a frst step towards trying newer interventions so as to develop updated clinical management guidelines.
基金Supported by Funding from the National Health and Medical Research Council of Australia,Nos.457575 and 632647 to Rangan GKthe Baltimore Polycystic Kidney Disease Research and Clinical Core Center,No.P30DK090868+2 种基金DK095036 to Watnick Tsupported by an Australian Postgraduate Award(University of Sydney)the Michael Stern Polycystic Kidney Disease Research Fellowship
文摘AIM： To determine the temporal expression and pattern of Rel/nuclear factor （NF）-κB proteins in renal tissue in polycystic kidney disease （PKD）. METHODS： The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofuorescence and immunoblot analysis in Lewis polycystic kidney rats （LPK, a genetic ortholog of human nephronopthsis-9） from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes （TNFa and CCL2） were determined. NF-κB was also histologically assessed in human PKD tissue.RESULTS： Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation （peaking at weeks 3 and 10 respectively）, and progressive interstitial fibrosis （with a smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards）. Rel/NF-κB proteins （phosphorylated-p105, p65, p50, c-Rel and RelB） were expressed in cystic epithelial cells （CECs） of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBa protein levels, and TNFa and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identifed in the CECs of LPK and human polycystic kidneys. CONCLUSION： Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases.
文摘Objective： To compare the efficacy of acupoint embedding combined with clomiphene with clomiphene alone in the treatment of patients with polycystic ovary syndrome （PCOS）. Methods： Sixty patients who met the diagnostic criteria of PCOS were randomly divided into the acupuncture-medicine combination （30 cases） and the single medicine （30 cases） groups. For a total of 4 menstrual cycles, patients in the acupuncture-medicine combination group were treated with acupoint embedding combined with oral clomiphene, whereas those in the single medicine group were treated with clomiphene only. Clinical efficacy of the two treatments was observed after 2 months of treatment, and body mass index （BMI）, number of menstrual cycles, luteinizing hormone （LH）, follicle stimulating hormone （FSH）, LH / FSH ratio, and serological levels of testosterone before and after treatment were analyzed. Results： Compared with the single medicine group, patients in the acupuncture-medicine group showed lower BMI （24.3 ± 1.6 vs 26.1 ± 1.8） and higher number of menstrual cycles （3.6 ± 1.5 vs 2.8 ± 1.2）; the differences were statistically significant （P = 0.018, P = 0.025）. LH （9.53 ± 5.46 vs 12.29 ± 5.67） and LH / FSH （1.02 ± 0.57 vs 1.45 ± 0.23） levels were significantly decreased （P = 0.041, P = 0.039）. Compared to before treatment, BMI （24.3 ± 1.6 vs 27.6 ± 1.4） was lower and the number of menstrual cycles was higher （3.6 ± 1.5 vs 1.8 ± 0.8） after treatment; the differences were statistically significant （P = 0.034, P = 0.024）. The levels of LH （9.53 ± 5.46 vs 18.12 ± 11.04） and LH / FSH （1.02 ± 0.57 vs 2.38 ± 1.09） were significantly decreased （P = 0.007 P = 0.005）. Total effective rates were 76.67% and 70% in the acupuncture-medicine combination and single medicine groups, respectively; the difference between the two groups was statistically significant （P = 0.043）. Conclusion： Acupoint embedding combined with clomiphene in the treatment of PCOS could downregulate BMI, LH, and LH / FSH ratio, and increase the number of menstrual cycles.
