Yi Sui

Eight-year survival of AIDS patients treated with Chinese herbal medicine.

Treatment of acquired immunodeficiency syndrome (AIDS) currently relies on the use of antiretroviral drugs. Little is known about Chinese herbal medicine (CHM) outcomes in patients living with AIDS. We conducted a cohort study to investigate long-term survival among CHM-treated AIDS patients. Patients were poor farmers who contracted HIV-1 infection when selling blood in the 1990s. Symptoms of AIDS included recurring respiratory tract infections with a clinical diagnosis of pneumonia, swollen lymph nodes and weight loss. 385 patients with AIDS were included and 165 of them used a 16-herb formula for 14 days to 9 months. The eight-year survival rate was 87% for the CHM users and 34% for the non-users (increased survival probability for CHM user, 9.6; 95% CI = 6.0-15.4; p < 0.0001). Survival probability further increased 14.6-fold (95% CI = 8.2-26.1), when excluding the users who received CHM for less than three months. Zero deaths were found in patients who used CHM for six to nine months. All the survivors regained their body weight and none of them experienced a relapse of AIDS or any severe adverse events. After the CHM treatment for an average of 3.6 months, the plasma HIV load was 74.7% lower (paired t-test, p = 0.151) and the number of blood CD4+ lymphocytes increased from 253 to 314 (paired t-test, p = 0.021). Without life-long medication, CHM may be beneficial for long-term survival of AIDS patients.

Common Mechanism of Pathogenesis in Gastrointestinal Diseases Implied by Consistent Efficacy of Single Chinese Medicine Formula: A PRISMA-Compliant Systematic Review and Meta-Analysis

AbstractGastrointestinal (GI) disorders often manifest similar symptoms with overlapping clinical diagnosis and unmet medical needs. Traditional Chinese medicine (TCM) has history-proven benefits for GI diseases; albeit language barrier prevents Western readers from accessing the original reports in Chinese. The TCM formula Si-Ni-San (SNS) consists of 4 herbs targeting on homeostatic disturbances characterized by “reflux” and “irritable” problems. Here we used SNS as a therapeutic tool to explore the common mechanisms of pathogenesis in non-neoplastic GI diseases.Data sources from PUBMED, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for clinical trials. Comparisons were SNS as intervention and Western conventional medicine as control, which treat patients with upper GI disorders (gastroesophageal reflux disease, peptic ulcer, chronic gastritis, duodenogastric reflux), lower GI diseases (irritable bowel syndrome, ulcerative colitis), and functional dyspepsia. Participants and studies in accordance with the Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement were eligible. We used the Jadad scale to assess methodological qualities, the fixed or random-effect model to evaluate therapeutic efficacy, and the funnel plots to explore publication bias. Outcome was clinical efficacy defined by symptom relief with normal GI endoscopy, radiology, and pathology.We included 83 studies involving 7762 participants: 1708 versus 1397 of the upper GI disorders in 34 studies, 901 versus 768 of the lower GI diseases in 19 studies, 1641 versus 1348 of functional dyspepsia in 30 studies, and 328 versus 287 of relapse rate in 8 studies. Six studies had a Jadad score >2 points and the rest were <2 points. Pooled data showed significant efficacy of SNS for the upper GI disorders (odds ratio [OR] = 3.9, 95% confidence interval [CI] = 3.09–4.92), lower GI diseases (OR = 4.91, 95% CI = 3.71–6.51), and functional dyspepsia (N = 2989; OR = 3.94, 95% CI = 3.17–4.90). The relapse rate was 12.9% for SNS, significantly <46.5% for conventional therapies (OR = 0.16, 95% CI = 0.11–0.25).The consistent efficacy of the single TCM formula implicates common mechanisms of pathogenesis in GI disorders.

Changes of regulatory T cells, transforming growth factor-beta and interleukin-10 in patients with type 1 diabetes mellitus: A systematic review and meta-analysis.

Regulatory T lymphocyte cells (Treg) associated with interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) have implicated in the development of type 1 diabetes mellitus (T1DM), yet the existing evidence remains unclear. Hereby we performed a systematic review and meta-analysis to characterize the changes in T1DM patients. A total of 1407 T1DM patients and 1373 healthy controls from 40 case-control studies were eventually included in the pooling analysis. Compared with the controls, T1DM patients had decreased frequency of CD4(+)CD25(+)Treg (p=0.0003), CD4(+)CD25(+)Foxp3(+)Treg (p=0.020), and the level of TGF-β (p=0.030). Decrease in IL-10 (p=0.14) was not significant. All the changes remained significant when the studies with low NOS scores and publication bias were excluded. In conclusion, peripheral Treg and serum TGF-β are reduced in type 1 diabetes mellitus whereas changes in serum IL-10 are not significant.

Renal Kallikrein Activation and Renoprotection after Dual Blockade of Renin-Angiotensin System in Diet-Induced Diabetic Nephropathy

Purpose. The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS) on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN). Methods. Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histopathology, function and immunohistochemical stain of kallikrein, macrophage marker CD68, and profibrotic markers transforming growth factor- (TGF-) β and α-smooth muscle action (SMA). Results. DN rats showed enlarged kidneys with glomerulosclerosis, interstitial chronic inflammation and fibrosis, and proteinuria. All the pathological damage and functional impairments were improved after the RAS blockades (all P < 0.05). Compared with monotherapy, combined treatment further alleviated the kidney impairments in parallel to increased tubular immunoreactivity for kallikrein and decreased immunopositive cells for CD68, TGF-β, and α-SMA. Conclusion. The renoprotective effects of the dual RAS blockade in diabetic nephropathy may be attributed to improved tubular kallikrein expression and interstitial inflammatory response.

A meta-analysis of renal outcomes in living kidney donors.

AbstractGiven the increased burden of end-stage renal disease (ESRD), renal outcomes of kidney donation by living donors are of particular interest. PubMed, ProQuest, MEDLINE, EMBASE, Chinese national knowledge infrastructure, and Wanfang databases were searched for clinical outcomes of living kidney donors (LKDs) including renal death, ESRD, proteinuria/albuminuria, and renal function after donation. We included 62 studies from 19 countries involving 114,783 kidney donors and nondonors to evaluate the renal consequences less than 6 months, 6 months to 5 years, 5 to 10 years, and 10 years onward after donation. The pooled data showed that uninephrectomy significantly decreased glomerular filtration rate and creatinine clearance rate in parallel with increased serum creatinine concentration (all P < 0.05). The drastic changes in renal function occurred within 6 months rather than 5 to 10 years after donation. Ten years and onward, rate of proteinuria/albuminuria increased gradually: microalbuminuria from 5.3% to 20.9%, proteinuria from 4.7% to 18.9%, and overt proteinuria from 2.4% to 5.7% (all P < 0.05). Prevalence of ESRD was 1.1%. All-cause mortality was 3.8% and all the renal deaths on average occurred 10 years postnephrectomy. LKDs might have aggravated glomerular filtration and creatinine clearance within 6 months after donation. Five years and onward, albuminuria, proteinuria, ESRD, and death might be the major concerns of LKDs. Long-term studies may clarify the survival time after donation.

Renin–angiotensin system blockade for the risk of cancer and death

Introduction: The effects of renin–angiotensin system blockade with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) on cancer remain inconsistent. Methods: We searched existing databases from 1960 to August 2015, for randomised controlled trials and observational studies (case–control studies and cohort studies) of ARB/ACEI therapy with a minimal one year of follow-up. Outcomes were incidence and mortality of cancer. Results: We included 14 randomised controlled trials and 17 observational studies of 3,957,725 participants (350,329 ARB/ACEI users). The users had a lower incidence of cancer in the observational studies (RR 0.82, 95% CI 0.73–0.93) but not in the randomised controlled trials (RR 1.00, 95% CI 0.92–1.08). The protection persisted for lung cancer (RR 0.85, 95% CI 0.75–0.97) but not for other sites of cancer. The relative risk of cancer associated with renin–angiotensin system blockade was reduced along with time of follow-up. Mortality reduction with ARB/ACEI was marginally significant in the observational studies (RR 0.71, 95% CI 0.55–0.93) but not in the randomised controlled trials (RR 0.99, 95% CI 0.89–1.09). Conclusions: The significant benefits of renin–angiotensin system blockade observed in case–control studies and cohort studies might diminish in randomised controlled trials. Clinical design, site of cancer and duration of follow-up may affect the clinical outcomes.

Cross-talk between AMP-activated protein kinase and renin–angiotensin system in uninephrectomised rats

Introduction: The renal renin–angiotensin system (RAS) and the ultrasensitive energy sensor AMP-activated protein kinase (AMPK) have been implicated in normal and aberrant states of the kidney, but interaction between the RAS and AMPK remains unknown. Methods: Ninety-six rats were stratified into four groups: sham, uninephrectomised, uninephrectomised rats treated with the angiotensin-converting enzyme inhibitor lisinopril or the angiotensin receptor blocker losartan. Histopathological examination at 9 months post-operation and biochemical measurements at 3, 6 and 9 months were performed for changes in renal structure and function. The expression of AMPK and angiotensin II at 9 months was detected by immunofluorescence microscopy and western blot. Results: Compared with sham rats, uninephrectomised rats demonstrated progressive glomerulosclerosis, tubular atrophy with cast formation and chronic inflammatory infiltration, in parallel to elevated serum urea, creatinine, urine total protein to creatinine ratio and reduced serum albumin. Overexpression of angiotensin II coexisted with a 85.6% reduction of phosphorylated to total AMPK ratio in the remnant kidney of uninephrectomised rats. RAS blockade by the angiotensin-converting enzyme inhibitor or angiotensin receptor blocker substantially normalised AMPK expression, morphological and functional changes of the remnant kidney. Conclusions: Uninephrectomy-induced RAS activation and AMPK inhibition in the remnant kidney could be substantially corrected by RAS blockade, suggesting a cross-talk between AMPK and RAS components in uninephrectomised rats.

Interaction of renin–angiotensin system and adenosine monophosphate–activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats:

Renin–angiotensin system and adenosine monophosphate–activated protein kinase signaling pathway both play important roles in carcinogenesis, but the interplay of renin–angiotensin system and adenosine monophosphate–activated protein kinase in carcinogenesis is not clear. In this study, we researched the interaction of renin–angiotensin system and adenosine monophosphate–activated protein kinase in renal carcinogenesis of uninephrectomized rats. A total of 96 rats were stratified into four groups: sham, uninephrectomized, and uninephrectomized treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Renal adenosine monophosphate–activated protein kinase and its downstream molecule acetyl coenzyme A carboxylase were detected by immunohistochemistry and western blot at 10 months after uninephrectomy. Meanwhile, we examined renal carcinogenesis by histological transformation and expressions of Ki67 and mutant p53. During the study, fasting lipid profiles were detected dynamically at 3, 6, 8, and 10 months. The results indicated that adenosine monophosphate–activated protein kinase expression in uninephrectomized rats showed 36.8% reduction by immunohistochemistry and 89.73% reduction by western blot. Inversely, acetyl coenzyme A carboxylase expression increased 83.3% and 19.07% in parallel to hyperlipidemia at 6, 8, and 10 months. The histopathology of carcinogenesis in remnant kidneys was manifested by atypical proliferation and carcinoma in situ, as well as increased expressions of Ki67 and mutant p53. Intervention with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker significantly prevented the inhibition of adenosine monophosphate–activated protein kinase signaling pathway and renal carcinogenesis in uninephrectomized rats. In conclusion, the novel findings suggest that uninephrectomy-induced disturbance in adenosine monophosphate–activated protein kinase signaling pathway resulted in hyperlipidemia and carcinogenesis in tubular epithelial cells, which may be largely attenuated by renin–angiotensin system blockade, implying the interaction of renin–angiotensin system and adenosine monophosphate–activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats.