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.

Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.

Total Flavonoids of Bidens pilosa Ameliorates Bone Destruction in Collagen-Induced Arthritis.

Rheumatoid arthritis is a chronic autoimmune disease characterized by the infiltration of synovial inflammatory cells and progressive joint destruction. Total flavonoids of Bidens pilosa have been used against inflammation in rheumatoid arthritis, but its role in bone destruction remains to be explored. The aim of this paper was to study whether total flavonoids of B. pilosa relieve the severity of collagen-induced arthritis in rats, particularly whether it regulates the production of proinflammatory cytokines and the receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin signaling pathway. In this research, a collagen-induced disease model was induced in adult rats by subcutaneous injection of collagen II. Total flavonoids of B. pilosa at different doses (40, 80, and 160 mg/kg/d) were administered intragastrically, while methotrexate (1 mg/kg/w) was injected intraperitoneally as a positive control. Paw swelling, arthritis score, and body weight were assessed and evaluated. The severity of joint damage was determined using X-ray and confirmed by histopathology. The expression levels of receptor activator of nuclear factor-κB ligand, osteoprotegerin, IL-1ß, IL-17, and TNF in the serum and tissue were assayed using ELISA and immunohistochemistry. We found that total flavonoids of B. pilosa attenuated collagen-induced arthritis at the macroscopic level, and total flavonoids of B. pilosa-treated rats showed reduced paw swelling, arthritis scores, and X-ray appearance of collagen-induced arthritis in addition to improved histopathological results. These findings were consistent with reduced serum and tissue receptor activator of nuclear factor-κB ligand, TNF, IL-1ß, and IL-17 levels but increased osteoprotegerin levels. Our data suggest that total flavonoids of B. pilosa attenuate collagen-induced arthritis by suppressing the receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin pathway and the subsequent production of proinflammatory cytokines. In addition, total flavonoids of B. pilosa may be a promising therapeutic candidate for the management of rheumatoid arthritis.

Leflunomide plus low-dose prednisone in patients with progressive IgA nephropathy: a multicenter, prospective, randomized, open-labeled, and controlled trial.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common cause of glomerulonephritis worldwide, and the optimal approach to its treatment remains a significant challenge. METHODS: We did a prospective, randomized, open-labeled, multicenter, controlled trial, comprised of 3-month run-in, 12-month treatment, and 12-month follow-up phases. After 3-month run-in phase, patients with biopsy-confirmed IgAN at risk of progression were randomly allocated to LEF plus low-dose prednisone (LEF + prednisone group) or conventionally accepted-dose prednisone [prednisone(alone) group] Our primary outcome was 24-h urine protein excretion (UPE) and secondary outcomes were serum albumin (sALB), serum creatinine (Scr), and eGFR. Safety was evaluated in all patients who received the trial medications. RESULTS: One hundred and eight patients [59 in LEF + prednisone group, 49 in prednisone (alone) group]were enrolled and finished their treatment and follow-up periods. There is no significant difference in the baseline level between the two groups. Compared with baseline, both groups showed a significant decrease in 24-h UPE (p < 0.01) and increase in sALB (p < 0.01), with stable Scr and eGFR throughout the 12-month treatment period. What's more, these effects were sustained through the 12-month follow-up period. However, there was no difference in 24-h UPE, sALB, Scr, and eGFR between the two groups (p > 0.05). At 12 months, a difference in overall response rate, relapsing rate, and incidence of adverse events between the two groups was not significant. CONCLUSIONS: The efficacy and safety of LEF plus low-dose prednisone and conventionally accepted-dose prednisone in the treatment of progressive IgAN are comparable.

Improvement of membranous nephropathy by inhibition of miR-193a to affect podocytosis via targeting WT1.

The objective of this paper was to explore the role and molecular mechanism of miR-193a in membranous nephropathy (MN). Experimental rats and podocytes were randomly divided into four groups: control, MN, miR-NC, and miR-193a inhibitor groups. The relative mRNA level of miR-193a was determined. The mRNA level and protein expression of PODXL, NPHS1, and Notch1 were determined by real-time polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. The mRNA level and protein expression of WT1 in podocytes were also determined by RT-PCR and Western blot analysis. The relative mRNA level of miR-193a in the MN group was significantly higher than that in the control group, and inhibition of miR-193a inhibited the increase successfully. Inhibition of miR-193a inhibited renal injury, podocyte injury, and tissue cell apoptosis resulting from MN. The expression of PODXL, NPHS1, and Notch1 was decreased in the MN group, while the expression was increased in the miR-193a inhibitor group. WT1 was verified as a target gene of miR-193a and the expression of WT1 increased after inhibition of miR-193a. Inhibition of miR-193a by targeting WT1 could inhibit renal function injury, renal tissue cell apoptosis, and podocytosis.

Outcomes and practice patterns with hemodiafiltration in Shanghai: a longitudinal cohort study.

BACKGROUND: Globally, there is increased clinical interest and uptake of hemodiafiltration (HDF) for increased removal of uremic toxins. To date, there has been no epidemiological analysis of HDF in China. We present HDF practice patterns and associated mortality risk in Shanghai. METHODS: This is an observational, prospectively collected, retrospective analysis of 9351 Chinese patients initiating hemodialysis in Shanghai from 2007 to 2014. The primary exposure was hemodialysis sub-modality at inception, classified into hemodiafiltration (HDF) and hemodialysis (HD), with adjustment for concommitant hemoperfusion. The primary outcome was patient mortality. We used Cox proportional hazards regression and Fine and Gray's proportional subhazards regression, with multiple imputation of missing co-variates by the chained equation method, adjusting for demographic and clinical variables. RESULTS: Overall, patients in the cohort were younger, with a more males, and with a lower body mass index when compared to corresponding non-Asian cohorts. Mortality rate was low although it doubled over the period of observation. HDF utilization increased from 7% of patients in 2007 to 42% of patients in 2014. The majority of patients received HDF once a week. The adjusted hazard ratio of death (95% confidence intervals) for HDF versus HD was 0.85 (0.71-1.03), and corresponding sub-hazard ratio 0.86 (0.71-1.03). There was strong effect modification by age. In those aged 40-60 years, the hazard ratio (95% confidence intervals) was 0.65 (0.45-0.94), and sub-hazard ratio also 0.65 (0.45-0.95). CONCLUSIONS: Our study has certain limitations resulting from the limited number of co-variates available for modelling, missing data for some co-variates, and the lack of verification of data against source documentation. Notwithstanding, there is evidence of clinical benefit from HDF in China, and potential to improve patient outcomes through the greater removal of middle and larger uremic solutes.

A Telemedicine-Based Registration System for the Management of Renal Anemia in Patients on Maintenance Hemodialysis: Multicenter Study.

BACKGROUND: Renal anemia is one of the most important complications in patients on maintenance hemodialysis (MHD). Telehealth-based dialysis registration systems have the advantage of real-time monitoring and have gradually been applied to the management of chronic diseases. OBJECTIVE: The objective of our study was to evaluate the impact of a telehealth-based dialysis registration system on patients on MHD in terms of renal anemia control. METHODS: The Red China project aimed to develop a dialysis registration system based on the WeChat mobile platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, and baseline creatinine levels were recorded using this system. In addition, the hemoglobin and hematocrit levels were recorded monthly. The platform then generated a hemoglobin and hematocrit statistics report for each hemodialysis center monthly, including the detection rate, target rate, and distribution of hemoglobin and released it to physicians via the WeChat mobile phone app. The physicians were then able to treat the individual's anemia appropriately by changing the doses of erythropoiesis-stimulating agents or iron use on the basis of this report. We analyzed the demographic and baseline laboratory parameters, detection rate, target rate, and average level and distribution of hemoglobin 28 months after the launch of the project. RESULTS: A total of 8392 patients on MHD from 28 hemodialysis centers in Shanghai were enrolled from June 2015 to October 2017. The detection rate of hemoglobin increased from 54.18% to 73.61% (P<.001), the target rate of hemoglobin increased from 47.55% to 56.07% (P<.001), and the mean level of hemoglobin increased from 10.83 (SD 1. 60) g/dL to 11.07 (SD 1.60) g/dL (P<.001). In addition, the proportion of patients with hemoglobin levels ≥11 g/dL but <13 g/dL increased from 40.40% to 47.48%. CONCLUSIONS: This telehealth-based dialysis registration system can provide timely reporting of the anemia status in patients on MHD, which may improve the awareness of anemia and the attention to and compliance with anemia monitoring.

Caproyl-Modified G2 PAMAM Dendrimer (G2-AC) Nanocomplexes Increases the Pulmonary Absorption of Insulin.

We aimed to investigate the absorption-enhancing effect (AEE) of caproyl-modified G2 PAMAM dendrimer (G2-AC) on peptide and protein drugs via the pulmonary route. In this study, G2 PAMAM dendrimer conjugates modified with caproic acid was synthesized, the pulmonary absorption of insulin as models with or without G2-AC were evaluated. The results indicated that G2-AC6 exhibited a greatest AEE for insulin in various caproylation levels of G2-AC. G2-AC6 could significantly enhance the absorption of insulin, and the AEE of G2-AC6 was concentration-dependent. In toxicity tests, G2-AC6 displayed no measurable cytotoxicity to the pulmonary membranes over a concentration range from 0.1% (w/v) to 1.0% (w/v). Measurements of the TEER and permeability showed that G2-AC6 significantly reduced the TEER value of CF and increased its Papp value. The results suggested that G2-AC6 could cross epithelial cells by means of a combination of paracellular and transcellular pathways. These findings suggested G2-AC6 at lower concentrations (below 1.0%, w/v) might be promising absorption enhancers for increasing the pulmonary absorption of peptide and protein drugs.

[Effect of HPMCAS/curcumin amorphous solid dispersion in enhancing dissolution and chemical stability of curcumin].

To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.

Recent Advances in Traditional Chinese Medicine for Kidney Disease.

Because current treatment options for chronic kidney disease (CKD) are limited, many patients seek out alternative therapies such as traditional Chinese medicine. However, there is a lack of evidence from large clinical trials to support the use of traditional medicines in patients with CKD. Many active components of traditional medicine formulas are undetermined and their toxicities are unknown. Therefore, there is a need for research to identify active compounds from traditional medicines and understand the mechanisms of action of these compounds, as well as their potential toxicity, and subsequently perform well-designed, randomized, controlled, clinical trials to study the efficacy and safety of their use in patients with CKD. Significant progress has been made in this field within the last several years. Many active compounds have been identified by applying sophisticated techniques such as mass spectrometry, and more mechanistic studies of these compounds have been performed using both in vitro and in vivo models. In addition, several well-designed, large, randomized, clinical trials have recently been published. We summarize these recent advances in the field of traditional medicines as they apply to CKD. In addition, current barriers for further research are also discussed. Due to the ongoing research in this field, we believe that stronger evidence to support the use of traditional medicines for CKD will emerge in the near future.

Renoprotective effect of combined inhibition of angiotensin-converting enzyme and histone deacetylase.

The Connectivity Map database contains microarray signatures of gene expression derived from approximately 6000 experiments that examined the effects of approximately 1300 single drugs on several human cancer cell lines. We used these data to prioritize pairs of drugs expected to reverse the changes in gene expression observed in the kidneys of a mouse model of HIV-associated nephropathy (Tg26 mice). We predicted that the combination of an angiotensin-converting enzyme (ACE) inhibitor and a histone deacetylase inhibitor would maximally reverse the disease-associated expression of genes in the kidneys of these mice. Testing the combination of these inhibitors in Tg26 mice revealed an additive renoprotective effect, as suggested by reduction of proteinuria, improvement of renal function, and attenuation of kidney injury. Furthermore, we observed the predicted treatment-associated changes in the expression of selected genes and pathway components. In summary, these data suggest that the combination of an ACE inhibitor and a histone deacetylase inhibitor could have therapeutic potential for various kidney diseases. In addition, this study provides proof-of-concept that drug-induced expression signatures have potential use in predicting the effects of combination drug therapy.

Therapeutic use of traditional Chinese herbal medications for chronic kidney diseases.

Traditional Chinese herbal medications (TCHMs) are frequently used in conjunction with western pharmacotherapy for treatment of chronic kidney diseases (CKD) in China and many other Asian countries. The practice of traditional Chinese medicine is guided by cumulative empiric experience. Recent in vitro and animal studies have confirmed the biological activity and therapeutic effects of several TCHMs in CKD. However, the level of evidence supporting TCHMs is limited to small, nonrandomized trials. Due to variations in the prescription pattern of TCHMs and the need for frequent dosage adjustment, which are inherent to the practice of traditional Chinese medicine, it has been challenging to design and implement large randomized clinical trials of TCHMs. Several TCHMs are associated with significant adverse effects, including nephrotoxicity. However, reporting of adverse effects associated with TCHMs has been inadequate. To fully realize the therapeutic use of TCHMs in CKD, we need molecular studies to identify active ingredients of TCHMs and their mechanism of action, rigorous pharmacologic studies to determine the safety and meet regulatory standards required for clinical therapeutic agents, and well-designed clinical trials to provide evidence-based support of their safety and efficacy.

Efficacy and safety of traditional chinese medicine (Shenqi particle) for patients with idiopathic membranous nephropathy: a multicenter randomized controlled clinical trial.

BACKGROUND: To compare the safety and efficacy of the traditional Chinese medicine Shenqi particle and standard therapy with prednisone and cyclophosphamide (control) in adult patients with idiopathic membranous nephropathy (IMN). STUDY DESIGN: Open-label, multicenter, parallel, randomized, controlled clinical trial. SETTING & PARTICIPANTS: From April 2008 to February 2011, a total of 190 patients with biopsy-proven IMN from 7 hospitals in China participated in the study. All patients had nephrotic syndrome with estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m(2). INTERVENTION: Shenqi particle (9.6 g 3 times per day) or prednisone (1 mg/kg/d tapering to 0.17 mg/kg/d) and cyclophosphamide (total dose of 9-12 g per square meter of body surface area) for 48 weeks. OUTCOMES: Primary outcomes included complete remission, defined as proteinuria (24-hour urine protein excretion) ≤0.3 g/d, or partial remission, defined as proteinuria with protein excretion >0.3-<3.5 g/d and a 50% reduction from its peak value at 48 weeks. Secondary outcomes included serum albumin level, eGFR, doubling of serum creatinine level, end-stage renal disease, and death. RESULTS: Baseline values for proteinuria and eGFR were 5.34 ± 2.74 g/d and 84.0 ± 27.4 mL/min/1.73 m(2) for the Shenqi particle group and 5.33 ± 2.47 g/d and 83.8 ± 24.9 mL/min/1.73 m(2) for the control group, respectively. 132 patients (63 Shenqi particle group, 69 control group) completed the study. Change in urinary protein excretion in the Shenqi particle group was -3.01 (95% CI, -3.68 to -2.34) g/d, and in the control group, -3.28 (95% CI, -3.98 to -2.58) g/d; the mean difference between groups was 0.27 (95% CI, -0.70 to 1.23) g/d (P = 0.6). Changes in eGFR were 12.3 (95% CI, 4.99 to 19.6) mL/min/1.73 m(2) in the Shenqi particle group and -2.8 (95% CI, -10.32 to 4.77) mL/min/1.73 m(2) in the control group; the mean difference between groups was 15.1 (95% CI, 4.56 to 25.55) mL/min/1.73 m(2) (P = 0.005). Severe adverse events occurred in only the control group (14.5%) and included lung infection, liver injury, and pneumonia. LIMITATIONS: High rate of loss to follow-up and lack of observation period prior to the study. CONCLUSIONS: Shenqi particle may be a promising alternative therapy for adults with IMN and nephrotic syndrome.

Roflumilast enhances the renal protective effects of retinoids in an HIV-1 transgenic mouse model of rapidly progressive renal failure.

Retinoic acid decreases proteinuria and glomerulosclerosis in several animal models of kidney disease by protecting podocytes from injury. Our recent in vitro studies suggest that all-trans retinoic acid induces podocyte differentiation by activating the retinoic acid receptor-α (RARα)/cAMP/PKA/CREB pathway. When used in combination with all-trans retinoic acid, an inhibitor of phosphodiesterase 4 further enhanced podocyte differentiation by increasing intracellular cAMP. Additionally, we found that Am580, a specific RARα agonist, has similar renal protective effects as all-trans retinoic acid in a rederived colony of HIV-1 transgenic mice with rapidly progressive renal failure (HIV-Tg) that mimics human HIV-associated nephropathy. Treatment with either the inhibitor of phosphodiesterase 4, roflumilast, or Am580 significantly reduced proteinuria, attenuated kidney injury, and improved podocyte differentiation in these HIV-Tg mice. Additional renal protective effects were found when roflumilast was combined with Am580. Consistent with the in vitro data, glomeruli from HIV-Tg mice treated with both Am580 and roflumilast had more active phosphorylated CREB than with either agent alone. Thus, phosphodiesterase 4 inhibitors could be used in combination with RARα agonists to provide additional renal protection.

Astragaloside IV attenuates complement membranous attack complex induced podocyte injury through the MAPK pathway.

Membranous nephropathy (MN) is the most common cause of idiopathic nephrotic syndrome in adults and the cause is known to be due to the injury of podocytes located in the glomeruli. Astragalus membranaceus has been used for the treatment of patients with MN in China for a long time. The beneficial effect of Astragalus membranaceus on proteinuria of patients with MN has been well documented. However, the mechanism of astragalus membranaceu in alleviation of MN is still not completely understood. Therefore, in the current study, we employed a podocyte injury model induced by complement membranous attack complex to examine the mechanism of astragalus membraneceus in the treatment of MN. We found that complement membranous attack complex could increase lactate dehydrogenase (LDH) release from podocytes and astragaloside IV (AS-IV) could prevent LDH release from podocytes in a time- and dose-dependent pattern. Moreover, AS-IV restored podocyte morphology and cytoskeleton loss induced by complement membranous attack complex. Furthermore, AS-IV was able to reduce phosphorylation of JNK and ERK1/2 induced by complement membranous attack complex. In conclusion, the mechanism of Astragalus membranaceus in the treatment of MN may be related to its attenuation of podocyte injury through regulation of cytoskeleton and mitogen activated protein kinase.

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.

[Clinical observation of Shen No. 9 Recipe with Qingre Moshen Granule on the treatment of idiopathic membranous nephropathy after treated by multiple Western drugs with no efficacy].

OBJECTIVE: To observe the clinical efficacy of Shen No. 9 Recipe (SR) combined with Qingre Moshen Granule (QMG) in treatment of idiopathic membranous nephropathy (IMN) patients with no efficacy after treated by hormone or immunosuppressive agent, and further to explore the possible mechanism of this method in treatment of IMN by detecting the cellular immune function and cytokine interleukin-2 (IL-2). METHODS: Forty-four IMN patients with no efficacy after treated by multiple Western drugs were recruited from October 2007 to October 2009. They took SR (one dosage daily, oral administration in two portions) and QMG (each package each time, thrice daily) for 24 weeks. The 24-h urine protein, glomerular filtration rate (GFR), plasma albumin (Alb), serum creatinine (SCr), urea nitrogen (BUN), triglyceride (TG), serum total cholesterol (TC), levels of cellular immune function (CD4+, CD8+, CD4+/CD8+ ratio), and IL-2 were detected before and after treatment. The changes of Chinese medicine syndrome and adverse reactions were observed and recorded. RESULTS: After treatment the complete remission rate, the basic remission rate, and the total effective rate was 4.5%, 68.2%, 84.1%, respectively. The total markedly-effective rate of Chinese medicine syndrome was 90.9%. The Chinese medicine syndrome was significantly lower than before treatment (P < 0.01). The 24-h urine protein obviously decreased (P < 0.01), Alb obviously increased (P < 0.01), levels of TC and TG obviously decreased (P < 0.01, P < 0.05). There was no obvious change in levels of SCr and BUN (P > 0.05). The GFR significantly increased (P < 0.05). CD4+ and the ratio of CD4+/CD8+ were obviously elevated (P < 0.01) and the CD8+ obviously decreased (P < 0.01). The expression level of IL-2 obviously increased, but it still was lower than the normal value, showing statistical difference (P < 0.01). CONCLUSIONS: SR + QMG showed definite efficacy in treatment of IMN patients with no efficacy after treated by multiple Western drugs. It could improve the level of cellular immunity and improve abnormal expression levels of IL-2.

The Amorphous Quercetin/ Hydroxypropylmethylcellulose Acetate Succinate Solid Dispersions Prepared by Co-Precipitation Method to Enhance Quercetin Dissolution.

HPMCAS-HF, HPMCAS-MF and HPMCAS-LF were used as carriers to prepare the amorphous solid dispersions (ASDs) of quercetin (Que) by co-precipitation. The Que ASD based on PVP K30 was prepared by solvent evaporation method. The ability of polymer to inhibit Que crystallization was evaluated. The study found the order of the ability of polymer to inhibit Que nucleation to be: HF > MF > LF > K30, and that to maintain Que supersaturation to be: HF > K30 > MF > LF. The prepared solid dispersions were characterized by IR, DSC and PXRD. Although HF was the most effective crystallization inhibitor, the release of the Que/HF ASD was poor and assigned to the carrier-controlled dissolution for the strong interactions between Que and HF. The Que/MF ASD exhibited better dissolution behavior compared to the Que/K30 ASD. The dissolution behavior of the Que ASD depended on the polymer-Que interactions and the ability of crystallization inhibition of the polymer.

The Efficacy and Safety of Rituximab for Childhood Steroid-Dependent Nephrotic Syndrome: A Systematic Review and Meta-Analysis.

Objectives: Rituximab (RTX), a possible alternative treatment option, is recognized as a new therapeutic hope for the treatment of steroid-dependent nephrotic syndrome (SDNS) in children. However, the efficacy and safety of RTX in the treatment of childhood SDNS are still controversial. The objective of this study was to evaluate the efficacy and safety of RTX treatment in children with SDNS. Study Design: Six randomized controlled trials (RCTs) and one retrospective comparative control study data from studies, performed before January 2021 were collected, from PubMed, Cochrane Library, Embase, and Web of Science. The studies evaluating the efficacy and safety of RTX in childhood SDNS were included. Results: Six RCTs and one retrospective comparative control study were included in our analysis. Compared with the control group, the RTX treatment group achieved a higher complete remission rate (OR = 5.21; 95% CI, 3.18-8.54; p < 0.00001), and we found significant differences between the two groups on serum albumin level (MD = 0.88; 95% CI, 0.43-1.33; p = 0.0001) and estimated glomerular filtration rate (MD = 6.43; 95% CI, 2.68-10.19; p = 0.0008). However, RTX treatment did not significantly lower serum creatinine levels nor did it significantly reduce the occurrence of proteinuria. In addition, we found no advantages with RTX on treatment safety. Conclusions: RTX has shown satisfactory characteristics in terms of efficacy and may be a promising treatment method for SDNS in children. However, the long-term effects have not been fully evaluated and should be further studied through randomized clinical trials.