Clinicopathological Characteristics and Outcomes of Immunoglobulin A Nephropathy with Different Types of Dyslipidemia: A Retrospective Single-Center Study.

INTRODUCTION: Immunoglobulin A nephropathy (IgAN) is one of the most common glomerulonephritic diseases in the world. Several lines of evidence have suggested that dyslipidemia is related to the disease progression and prognosis of IgAN. However, the study is scarce on the clinicopathological characteristics and outcomes of IgAN with dyslipidemia. METHODS: This study retrospectively analyzed 234 patients with biopsy-proven idiopathic IgAN at the Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, between January 2015 and June 2021. The participants were divided into dyslipidemia (n = 119) and non-dyslipidemia (n = 115), and the dyslipidemia group was also divided into the following 4 groups: hypertriglyceridemia group, hypercholesterolemia group, mixed hyperlipidemia group, and low high-density lipoprotein cholesterol group. The estimated glomerular filtration rate (eGFR) was estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS: The prevalence of dyslipidemia in IgAN patients in our center was 50.9% (119/234). The patients with dyslipidemia presented with higher systolic blood pressure (BP), diastolic BP, serum creatinine, uric acid, hemoglobin, proteinuria, and eGFR (p < 0.05). Proportions of males, hypertension, and chronic kidney disease stage 2∼5 were also higher in the dyslipidemia group (p < 0.05). Similarly, the pathological characteristics performed were worse in the dyslipidemia group. Most dyslipidemia patients had a higher percentage of mesangial hypercellularity (M1) and tubular atrophy/interstitial fibrosis (T1∼2) in the Oxford Classification's scoring system (p < 0.05). Multivariate logistic regression analysis revealed that male gender (odds ratio [OR] = 2.397, 95% confidence interval [CI]: 1.051-5.469, p = 0.038) and proteinuria (OR = 1.000, 95% CI: 1.000-1.001, p = 0.035) were possible risk factors for dyslipidemia. A total of 13 patients (13.8%) in the dyslipidemia group had an endpoint event, of which 6 patients (6.4%) had a ≥50% decrease in eGFR from baseline and 7 patients (7.4%) reached the end-stage renal disease stage. Kaplan-Meier survival curve analysis showed that patients in the dyslipidemia group had a worse outcome than those in the non-dyslipidemia group (log-rank test, p = 0.048). CONCLUSIONS: IgAN patients with dyslipidemia presented more severe clinicopathological characteristics. Male gender and proteinuria are significantly associated with the occurrence of dyslipidemia in IgAN patients. Patients in the dyslipidemia group had a worse prognosis than those in the non-dyslipidemia group, which may be essential for the disease management of IgAN and help identify the high-risk patients.

Improving Shelf Life and Content of Unsaturated Fatty Acids in Meat of Lambs Fed a Diet Supplemented with Grape Dregs.

This study was conducted to evaluate the potential effects of dietary grape residue levels on the slaughter indicators, meat quality, meat shelf-life, unsaturated fatty acid content, and expression of fatty acid deposition genes in the muscle of lambs. Sixty 30-month-old male Dorper and Small-Tailed Han F1 hybrid lambs were assigned to a single factor complete randomized trial design and fed with four different diets including 0%, 8%, 16%, and 24% grape dregs, respectively. The findings regarding meat production efficacy in the lambs revealed substantial differences. The control group showed notably lower dressing percentage, carcass weight, net meat weight, meat percentage concerning carcass, meat-to-bone ratio, relative visceral and kidney fat mass, and rib eye area compared to the other groups (p < 0.05). Additionally, the meat shearing force of lambs fed a diet with 16% grape pomace (GP) was significantly higher than that of the 24% GP group (p < 0.05), while the 24 h meat color parameter a* value of the control group was notably higher than that of the 8% GP group (p < 0.05). In addition, compared to the control group, lambs fed with a diet containing 16% GP had higher levels of oleic acid (C18:1n-9c), linoleic acid (C18:2n-6c), behenic acid (C22:0), tricosanoic acid (C23:0), lignoceric acid (C24:0), and conjugated linoleic acid (CLA), at a ratio of ∑CLA/TFA, ∑n-6, ∑MUFA, and ∑PUFA in the longissimus dorsi muscle (p < 0.05), but the reverse case was applicable for Total Volatile Basic Nitrogen (TVB-N) content (p < 0.05). GP supplementation did not substantially affect the expression of stearoyl-CoA desaturase (SCD), peroxisome proliferator activated receptor alpha (PPARα), and peroxisome proliferator-activated receptor gamma (PPARγ) genes (p > 0.05). The findings indicated that incorporating grape dregs in the diets of fattening lambs leads to notable enhancements in meat production and the antioxidant capacity of lamb meat, and effectively extends the shelf life of the meat.

High-coverage targeted lipidomics could reveal lipid alterations and evaluate therapeutic efficacy of membranous nephropathy.

BACKGROUND: Membrane nephropathy (MN) often presents as nephrotic syndrome with characteristic lipid metabolism that could not be explained by lipid indicators commonly used in clinical practice. Studies have shown that invigorating spleen and qi, activating blood and detoxication in the treatment of MN is an effective method proved by randomized controlled clinical trial. However, the alterations of lipid profile before and after traditional Chinese medicine (TCM) treatment and the related lipid markers that affect the therapeutic effect have not been fully clarified. METHODS: We analyzed plasma lipid profiles of 92 patients with MN before and after TCM treatment by high-coverage targeted lipidomics. RESULTS: 675 lipids were identified, of which 368 stably expressed lipids (coefficient of variation less than 30% and deletion value less than 10%) were eventually included for statistical analysis. 105 lipids were altered mainly including spingolipids, glycerides, glycerophosholipid, fatty acyl and steroids, among which, the abundance of ceramides (Cers), sphingomyelins (SMs), diacylglycerols (DGs), phosphatidylcholines (PCs) were lower than those before treatment with statistically significant difference. The WGCNA network to analyze the correlation between the collective effect and the therapeutic effect showed that the triglyceride (TG) molecules were most relevant to the therapeutic effect. Analysis of 162 triglyceride molecules showed that 11 TGs were significantly down-regulated in the effective group which were concentrated in carbon atom number of 52-56 and double bond number of 0-4. TGs molecules including TG56:2-FA20:0, TG56:2-FA20:1, TG56:3-FA20:0 and TG56:5-FA20:2 were most closely related to the therapeutic effect of TCM after adjusting the influence of clinical factors. ROC curve analysis showed that these four lipids could further improve the predictive efficacy of treatment based on clinical indicators. CONCLUSION: Our work demonstrated that the therapeutic effect of invigorating spleen and qi, activating blood and detoxication in the treatment of MN may be exerted by regulating lipid metabolism. High-coverage targeted lipidomics provided a non-invasive tool for discovery of lipid markers to improve the predictive efficacy of TCM therapy.

Traditional Chinese Medicine as an adjunct therapy in the treatment of idiopathic membranous nephropathy: A systematic review and meta-analysis.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome in adults involving multiple targets and factors. The effect of conservative nonimmunosuppressive or immunosuppressive therapies is unsatisfactory and with many side effects. Traditional Chinese medicine (TCM) can regulate immune function and improve kidney function. PURPOSE: To evaluate the total effective rate, curative rate, recurrence rate and adverse events of TCM alone or TCM as an adjunctive therapy for IMN. METHODS: Randomized controlled trials (RCT) comparing either TCM alone or the combination of TCM to western medicine (WM) therapies for patients with IMN were retrieved by searching English and Chinese database. Risk of bias summary was used to assess the methodological quality of eligible studies. Dichotomous data were presented using odds ratios (OR). The primary outcome measure was the total effective rate. Secondary outcomes included curative rate, recurrence rate and adverse events. RESULTS: 29 RCTs involving 1883 participants met the inclusion criteria. There was no statistically significant difference between the therapy of TCM alone and WM on the total effective rates (OR: 2.00; 95% CI: 0.80-4.98; P = 0.14) and curative rate (OR: 1.66; 95%CI: 0.66-4.22; p = 0.28). However, compared to basic treatment or immunosuppressive therapies alone, results showed that TCM as an adjunctive therapy had beneficial effects on the total effective rate (OR: 2.59; 95% CI: 1.38-4.86; P = 0.003 and OR: 3.01; 95% CI: 2.25-4.04; P < 0.00001) and curative rate (OR: 3.01; 95%CI: 1.24-7.28; p = 0.01 and OR: 1.73; 95%CI: 1.10-2.71; p = 0.02). In addition, the combination of TCM treatment could reduce the recurrence rate (OR: 0.28; 95% CI: 0.12-0.68; P = 0.004) and adverse reactions (OR: 0.38; 95% CI: 0.27-0.54; p < 0.00001). CONCLUSION: The results indicate that TCM is well-tolerated for the treatment of IMN. However, there remains a need for large-scale and high-quality trials.

Influence of a herbal preparation on the pharmacokinetics of highly active antiretroviral therapy drugs in rats.

Shenlin Fuzheng Capsule (SLFZC) is a herbal preparation used for HIV/AIDS in Guangxi, China. This study was designed to evaluate the influence of SLFZC on the pharmacokinetics of highly active antiretroviral therapy (HAART) drugs, zidovudine (3'-azido-3'-deoythymidine, AZT), 2',3'-dideoxy-3'-thiacytidine (3TC) and efavirenz (EFV). Thirty-six male SD rats were divided into three groups. Group A was given a combination of AZT, 3TC and EFV (AZT/3TC/EFV). Group B rats were given AZT/3TC/EFV simultaneously with SLFZC. Group C rats were given AZT/3TC/EFV 2h prior to SLFZC. Blood samples were collected at fixed time intervals. Plasma concentration of each antiretroviral drug was tested for calculation of pharmacokinetic parameters. There was significant difference among groups with respect to t1/2 for AZT (F=3.371, P<0.05), but the Student-Newman-Keuls (SNK) pairwise multiple comparison procedure showed no statistical differences in all pairwise comparisons (P>0.05). There were no significant differences among groups in terms of Cmax, T max, AUC0-12h and CL for AZT, and t1/2, Cmax, Tmax, AUC0-12h and CL for 3TC and EFV, respectively. The results indicate that SLFZC has little impact on pharmacokinetic properties of AZT, 3TC and EFV.

Impact of Herbal Preparations on Outcomes of Highly Active Antiretroviral Therapy: A One-Year Prospective Cohort Study.

OBJECTIVE: To investigate the impacts of two herbal preparations for human immunodeficiency virus/aquired immune deficiency syndrome (HIV/AIDS) patients, Shenling Fuzheng Capsule (, SLFZC) and Qingdu Capsule (, QDC), on the efficacy of highly active antiretroviral therapy (HAART). METHODS: HIV/AIDS patients met the criteria were all enrolled in a 1-year cohort study, in which patients receiving HAART alone were designated as Group A, those receiving HAART in combination with SLFZC were designated as Group B, and those receiving HAART in combination with QDC were designated as Group C, 100 cases in each group. The dose of SLFZC was 1.48 g (4 capsules), 3 times daily, and QDC 1.56 g (4 capsules), 3 times daily. T cell subsets, HIV RNA and HIV-1 drug resistance were detected at enrollment and 1 year after treatment. Patients were followed up every 3 months, during which side-effects and other clinical data were recorded. RESULTS: After 1-year treatment, the median increment in CD4 counts was 165.0, 178.0 and 145.0 cells/µL for Group A, B and C, respectively. HIV RNA was undetectable in 94% of patients in Group A, 96% in Group B and 92% in Group C. There were no differences regarding the increment in CD4 counts, HIV RNA and frequency of HIV-1 drug resistance mutations. Two of the 14 suspected side-effect symptoms, i.e. fatigue and dizziness, were lower in Groups B and C than in Group A (P<0.05, respectively) CONCLUSIONS: SLFZC and QDC do not have a negative impact on immunological and virological response to HAART; however, these preparations are not as potent in reducing HAART-associated side-effects as anticipated.

The Efficacy and Mechanism of Chinese Herbal Medicine on Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the most common microvascular complication of diabetes and is one of the main causes of end-stage renal disease (ESRD) in many countries. The pathological features of DKD are the hypertrophy of mesangial cells, apoptosis of podocytes, glomerular basement membrane (GBM) thickening, accumulation of extracellular matrix (ECM), glomerular sclerosis, and tubulointerstitial fibrosis. The etiology of DKD is very complicated and many factors are involved, such as genetic factors, hyperglycemia, hypertension, hyperlipidemia, abnormalities of renal hemodynamics, and metabolism of vasoactive substances. Although some achievements have been made in the exploration of the pathogenesis of DKD, the currently available clinical treatment methods are still not completely effective in preventing the progress of DKD to ESRD. CHM composed of natural products has traditionally been used for symptom relief, which may offer new insights into therapeutic development of DKD. We will summarize the progress of Chinese herbal medicine (CHM) in the treatment of DKD from two aspects. In clinical trials, the Chinese herbal formulas were efficacy and safety confirmed by the randomized controlled trials. In terms of experimental research, studies provided evidence for the efficacy of CHM from the perspectives of balancing metabolic disorders, reducing inflammatory response and oxidative stress, antifibrosis, protecting renal innate cells, and regulating microRNA and metabolism. CHM consisting of different ingredients may play a role in synergistic interactions and multiple target points in the treatment of DKD.

Melatonin supplementation during in vitro maturation of oocyte enhances subsequent development of bovine cloned embryos.

Oocyte quality, which is directly related to reprogramming competence, is a major important limiting factor in animal cloning efficiency. Compared with oocytes matured in vivo, in vitro matured oocytes exhibit lower oocyte quality and reprogramming competence primarily because of their higher levels of reactive oxygen species. In this study, we investigate whether supplementing the oocyte maturation medium with melatonin, a free radical scavenger, could improve oocyte quality and reprogramming competence. We found that 10-9 M melatonin effectively alleviated oxidative stress, markedly decreased early apoptosis levels, recovered the integrity of mitochondria, ameliorated the spindle assembly and chromosome alignment in oocytes, and significantly promoted subsequent cloned embryo development in vitro. We also analyzed the effects of melatonin on epigenetic modifications in bovine oocytes. Melatonin increased the global H3K9 acetylation levels, reduced the H3K9 methylation levels, and minimally affected DNA methylation and hydroxymethylation. Genome-wide expression analysis of genes in melatonin-treated and nontreated oocytes was also conducted by high-throughput RNA sequencing. Our results indicated that melatonin ameliorates oocyte oxidative stress and improves subsequent in vitro development of bovine cloned embryos.

[Pharmacokinetic Effect of Aikeqing Granule by Different Medication Ways on Zidovudine in HAART of Rats].

OBJECTIVE: To study pharmacokinetic effect of Aikeqing Granule (AG) by different medication ways on zidovudine (AZT) in highly active antiretroviral therapy ( HAART) of rats. METHODS: Totally 36 rats were administered with corresponding medications by gastrogavage, group I [HAART: AZT 31.5 mg/kg +3TC 31.5 mg/kg + Efavirenz (EFV) 63.0 mg/kg], group II (HAART+AG525 mg/kg), group III (HAART and AG 525 mg/kg after a 2-h interval). Drug concentrations of AZT were determined by high performance liquid chromatography-mass spectroscopy (HPLC-MS) before HAART, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h after HAART, respectively. Pharmacokinetic parameters [such as t1/2, Tmax, Cmax, AUCo-t, plasma clearance rate (CL)] were calculated by DAS2.0 Software. RESULTS: The-equation of linear regression of AZT was good, with the precision, coefficient of recovery, and stability definitely confirmed. AUC in group II and III was larger than that of group I. There was no statistical difference in t1/2, Tmax, Cmax, AUC0-12 h, or AUC0-∞ among groups (P > 0.05). CONCLUSION: AG combined HAART could enhance the Cmax of AZT.

[Treating HIV/AIDS patients by shenlin fuzheng capsule and qingdu capsule: an analysis of clinical effectiveness].

OBJECTIVE: To analyze the clinical effectiveness of Shenling Fuzheng Capsule (SFC) and Qingdu Capsule (QC) in treating HIV/AIDS patients. METHODS: Totally 220 patients with complete clinical data, who received consecutive treatment for 6 months were selected from the database. They were assigned to two groups whether they would rather receive antiretroviral drugs, the Chinese medicine (CM) treatment group and the integrative medicine (IM) group. The 129 patients in the CM group were treated with SFC or QC, while the 91 patients in the IM group were treated with SFC or QC combined highly active antiretroviral agents. Total score and single score of clinical symptoms and signs, Karnofsky Performance Status (KPS), and changes of body weight before treatment, 3 and 6 months after treatment were compared. CD4+ cell counts were compared between before treatment and 6 months after treatment. RESULTS: The total score of clinical symptoms and signs were lower at 3 and 6 months of treatment than before treatment respectively (P < 0.01). The single score of clinical symptoms and signs such as cough, weakness, shortness of breath, vomit, spontaneous perspiration, hair loss,and chest pain were also lowered at 3 and 6 months of treatment (P < 0.05, P < 0.01), and the KPS increased (P < 0.05). The body weight increased (P < 0.05) and CD4 cell counts decreased (P < 0.05) in the CM group. There was no statistical difference in body weight or CD4 cell counts in the IM group between before and after treatment. CONCLUSION: SFC and QC could improve clinical symptoms and signs of HIV/ AIDS patients, but failed to deter the decrease of CD4+ cell counts.