Optimizing analytical precision in the identification of synthetic cathinones and isomers: a comparative assessment of diverse GC-MS operating parameters.

Analyzing new psychoactive substances (NPSs) in forensic laboratories present a formidable challenge globally. Within illicit drug analysis, gas chromatography-mass spectrometry (GC-MS) emerges as a robust analytical tool. This study endeavors to assess and compare peak resolution in the analysis of illicit drugs, specifically focusing on 21 synthetic cathinones, encompassing 9 cathinone isomers. Varied GC-MS operating conditions, including distinct GC-MS columns and thermal gradients, were systematically employed for the simultaneous analysis of these synthetic cathinones. The study utilized HP-1 nonpolar and HP-5MS low-bleed columns to achieve optimal analyte resolution through modulation of GC-MS oven conditions. Mass spectra were meticulously recorded within a mass-to-charge (m/z) range spanning from 40 to 500 in full scan mode. The data showed that the cathinone isomers slightly differed in retention times and mass spectra. The GC oven conditions affected the peak resolution for chromatographic separation even with the same column. The peak resolution improved using a slower thermal gradient heat speed with a prolonged analysis time. Conclusively, the interplay of GC columns and thermal gradients emerged as pivotal factors impacting peak resolution in the analysis of illicit drugs. These empirical insights contribute to a nuanced understanding of peak resolution dynamics and facilitate the identification of synthetic cathinones, including their isomers, in seized materials through the judicious application of GC-MS methodologies.

Ameliorative effects of Modified Huangqi Chifeng decoction on podocyte injury via autophagy mediated by PI3K/AKT/mTOR and AMPK/mTOR pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Proteinuria is recognized as a risk factor for the exacerbation of chronic kidney disease. Modified Huangqi Chifeng decoction (MHCD) has distinct advantages in reducing proteinuria. Our previous experimental results have shown that MHCD can inhibit excessive autophagy. However, the specific mechanism by which MHCD regulates autophagy needs to be further explored. AIM OF THE STUDY: In this study, in vivo and in vitro experiments were conducted to further clarify the protective mechanism of MHCD on the kidney and podocytes by regulating autophagy based on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK)/mTOR signaling pathways. MATERIALS AND METHODS: By a single injection via the tail vein, Sprague-Dawley rats received Adriamycin (5 mg/kg) to establish a model of proteinuria nephropathy. They were divided into control, model, MHCD, 3-methyladenine (3 MA), 3 MA + MHCD, and telmisartan groups and were administered continuously for 6 weeks. The MHCD-containing serum was prepared, and a model of podocyte injury induced by Adriamycin (0.2 µg/mL) was established. RESULTS: MHCD reduced the 24-h urine protein levels and relieved pathological kidney damage. During autophagy in the kidneys of rats with Adriamycin-induced nephropathy, the PI3K/AKT/mTOR signaling pathway is inhibited, while the AMPK/mTOR signaling pathway is activated. MHCD antagonized these effects, thereby inhibiting excessive autophagy. MHCD alleviated Adriamycin-induced podocyte autophagy, as demonstrated using Pik3r1 siRNA and an overexpression plasmid for Prkaa1/Prkaa2. Furthermore, MHCD could activate the PI3K/AKT/mTOR signaling pathway while suppressing the AMPK/mTOR signaling pathway. CONCLUSIONS: This study demonstrated that MHCD can activate the interaction between the PI3K/AKT/mTOR and the AMPK/mTOR signaling pathways to maintain autophagy balance, inhibit excessive autophagy, and play a role in protecting the kidneys and podocytes.

Inhibition of excessive autophagy alleviates renal injury and inflammation in a rat model of immunoglobulin A nephropathy.

The pathogenesis of immunoglobulin A nephropathy (IgAN) is closely related to immunity and inflammation. The clinical process of IgAN varies greatly, making the assessment of prognosis challenging and limiting progress on effective treatment measures. Autophagy is an important pathway for the development of IgAN. However, the role of autophagy in IgAN is complex, and the consequences of autophagy may change during disease progression. In the present study, we evaluated the dynamic changes in autophagy during IgAN. Specifically, we examined autophagy in the kidney of a rat model of IgAN at different time points. We found that autophagy was markedly and persistently induced in IgAN rats, and the expression level of inflammation was also persistently elevated. The autophagy enhancer rapamycin and autophagy inhibitor 3-methyladenine were used in this study, and the results showed that 3-methyladenine can alleviate renal injury and inflammation in IgAN rats. Our study provides further evidence for autophagy as a therapeutic target for IgAN.

Ferroptosis is involved in passive Heymann nephritis in rats.

Ferroptosis is found to be involved in some experimental models of kidney diseases, but its role in membrane nephropathy (MN) is still unclear. The purpose of this study is to explore whether ferroptosis occurred in MN, and the role of ferritinophagy. In this study, passive Heymann nephritis (PHN) rats were induced by single tail vein injection of anti-Fx1A serum, and normal rats were used as control. The changes of 24 h urinary protein, serum biochemical parameters, renal pathological damage, iron content, lipid peroxidation parameters, ferroptosis markers, and ferritinophagy markers were evaluated in the two groups. Compared with the control group, PHN rats showed obvious proteinuria, hypoproteinemia, and hyperlipidemia. Besides, more severe renal pathological damage and higher Fe2+ levels were observed in PHN rats, and the levels of malondialdehyde (MDA) increased significantly, while the levels of superoxide Dismutase (SOD) and glutathione (GSH) decreased. In addition, the expression of glutathione peroxidase 4 (GPX4) in renal tissues of PHN rats decreased significantly, while the expression of transferrin receptor (TFR) and acyl-CoA synthetase long-chain family member 4 (ACSL4) increased. The expression of microtubule associated protein 1 light chain 3 (LC3) II/LC3I and nuclear receptor coactivator 4 (NCOA4) increased significantly. Therefore, our study shows that ferroptosis is involved in the pathological damage of MN, and companied by activation of ferritinophagy.

Integrated Chinese and Western medicine in the treatment of a patient with podocyte infolding glomerulopathy: A case report.

BACKGROUND: Podocyte infolding glomerulopathy (PIG) is a newly described and rare glomerular disease. To date, only approximately 40 cases have been reported globally. CASE SUMMARY: A 26-year-old female patient presented to our hospital with a complaint of intermittent edema of both lower limbs over the past 2 years. The patient was diagnosed with PIG. She was prescribed corticosteroid therapy in other hospitals during the initial stage, to which she had responded poorly and had developed femoral head necrosis. Therefore, we administered immunosuppressants, renin-angiotensin system inhibitors, combined with traditional Chinese medicine. The patient was followed for 1 year, during which her clinical condition improved. CONCLUSION: Integrated Chinese and Western medicine may be effective for PIG treatment, which requires active intervention to improve prognosis.

Effects and mechanisms of Chinese herbal medicine on IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN), is the main cause of end-stage renal disease, that causes serious physical and psychological burden to patients worldwide. Some traditional treatment measures, such as blocking the renin-angiotensin-aldosterone system, controlling blood pressure, and following a low-protein diet, may not achieve satisfactory results. Therefore, more effective and safe therapies for IgAN are urgently needed. PURPOSE: The aim of this review is to summarize the clinical efficacy of Chinese herbal medicines (CHMs) and their active ingredients in the treatment and management of IgAN based on the results of clinical trials, systematic reviews, and meta-analyses, to fully understand the advantages and perspectives of CHMs in the treatment of IgAN. STUDY DESIGN AND METHODS: For this review, the following electronic databases were consulted: PubMed, ResearchGate, Science Direct, Web of Science, Chinese National Knowledge Infrastructure and Wanfang Data, "IgA nephropathy," "traditional Chinese medicine," "Chinese herbal medicine," "herb," "mechanism," "Meta-analysis," "systematic review," "RCT" and their combinations were the keywords to search the relevant literature. Data were collected from 1990 to 2022. RESULTS: This review found that the active ingredients of CHMs commonly act on multiple signaling pathways in the clinical treatment of IgAN, mainly with antioxidant, anti-inflammatory and anti-fibrosis effects, and regulation of autophagy. CONCLUSION: Compared with the single-target therapy of modern medicine, CHMs can regulate the corresponding pathways from the aspects of anti-inflammation, anti-oxidation, anti-fibrosis and autophagy to play a multi-target treatment of IgAN through syndrome differentiation and treatment, which has good clinical efficacy and can be used as the first choice or alternative therapy for IgAN treatment. This review provides evidence and research direction for a comprehensive clinical understanding of the protective effect of Chinese herbal medicine on IgAN.

Potential benefits of spicy food consumption on cardiovascular outcomes in patients with diabetes: A cohort study of the China Kadoorie Biobank.

OBJECTIVES: Dietary capsaicin from spicy foods has potential benefits for those with cardiometabolic diseases (CMDs). However, to our knowledge there is no evidence linking spicy food consumption with cardiovascular outcomes in individuals with diabetes. The aim of this study was to explore the association between spicy food consumption and the incidence of major adverse cardiovascular events (MACEs) in individuals with diabetes from the CKB (China Kadoorie Biobank) study and to provide evidence-based dietary recommendations for those with CMDs. METHODS: This prospective study enrolled 26 163 patients from the CKB study who had diabetes without coronary heart disease, stroke, or cancer to our knowledge. Of the 26 163 patients enrolled, 17 326 never or rarely ate spicy food (non-spicy group), and 8837 ate spicy food ≥1 d/wk (spicy group). The primary outcomes were MACEs, including cardiac death, non-fatal myocardial infarction, and stroke. Cox proportional hazards models were used to estimate the hazard ratio (HR) of MACEs and their associated 95% confidence intervals (CIs). RESULTS: During a median follow-up of 8.5 y, MACEs occurred in 5465 participants (20.9%), with 3820 (22%) and 1645 (18.6%) cases occurring in the non-spicy and spicy groups, respectively. Spicy food consumption was independently associated with a decreased tendency for MACEs, with an adjusted HR of 0.94 (95% CI, 0.89-1.00; P = 0.041). Subgroup analysis showed consistency in the results that the regular spicy eating groups were associated with significantly lower incidence of MACEs than the non-spicy group. There was no statistical difference in the incidence of MACEs among the three different spicy eating frequency groups. CONCLUSION: This cohort study revealed that the consumption of spicy food was independently associated with a reduced incidence of adverse cardiovascular events in Chinese adults with diabetes, suggesting a beneficial effect on cardiovascular health. Further studies are needed to confirm the association between the consumption of different doses of spicy food and cardiovascular outcomes and the exact mechanism of action.

Ferroptosis: A new mechanism of traditional Chinese medicine compounds for treating acute kidney injury.

Acute kidney injury (AKI) is a major health concern owing to its high morbidity and mortality rates, to which there are no drugs or treatment methods, except for renal replacement therapy. Therefore, identifying novel therapeutic targets and drugs for treating AKI is urgent. Ferroptosis is an iron-dependent and lipid-peroxidation-driven regulatory form of cell death and is closely associated with the occurrence and development of AKI. Traditional Chinese medicine (TCM) has unique advantages in treating AKI due to its natural origin and efficacy. In this review, we summarize the mechanisms underlying ferroptosis and its role in AKI, and TCM compounds that play essential roles in the prevention and treatment of AKI by inhibiting ferroptosis. This review suggests ferroptosis as a potential therapeutic target for AKI, and that TCM compounds show broad prospects in the treatment of AKI by targeting ferroptosis.

Application of Self-Assembled Polyarylether Substrate in Flexible Organic Light-Emitting Diodes.

The structure used in this study is as follows: substrate/PMMA/ZnS/Ag/MoO3/NPB/Alq3/LiF/Al. Here, PMMA serves as the surface flattening layer, ZnS/Ag/MoO3 as the anode, NPB as the hole injection layer, Alq3 as the emitting layer, LiF as the electron injection layer, and aluminum as the cathode. The properties of the devices with different substrates were investigated using P4 and glass, developed in the laboratory, as well as commercially available PET. After film formation, P4 creates holes on the surface. The light field distribution of the device was calculated at wavelengths of 480 nm, 550 nm, and 620 nm using optical simulation. It was found that this microstructure contributes to light extraction. The maximum brightness, external quantum efficiency, and current efficiency of the device at a P4 thickness of 2.6 µm were 72,500 cd/m2, 1.69%, and 5.68 cd/A, respectively. However, the maximum brightness of the same structure with PET (130 µm) was 9500 cd/m2. The microstructure of the P4 substrate was found to contribute to the excellent device performance through analysis of the AFM surface morphology, film resistance, and optical simulation results. The holes formed by the P4 substrate were created solely by spin-coating the material and then placing it on a heating plate to dry, without any special processing. To confirm the reproducibility of the naturally formed holes, devices were fabricated again with three different emitting layer thicknesses. The maximum brightness, external quantum efficiency, and current efficiency of the device at an Alq3 thickness of 55 nm were 93,400 cd/m2, 1.7%, and 5.6 cd/A, respectively.

N-/T-Type vs. L-Type Calcium Channel Blocker in Treating Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Renin-angiotensin system (RAS) inhibitors and calcium channel blockers (CCB) are often used together in chronic kidney disease (CKD). The PubMed, EMBASE, and Cochrane Library databases were searched to identify randomized controlled trials (RCTs) in order to explore better subtypes of CCB for the treatment of CKD. This meta-analysis of 12 RCTs with 967 CKD patients who were treated with RAS inhibitors demonstrated that, when compared with L-type CCB, N-/T-type CCB was superior in reducing urine albumin/protein excretion (SMD, -0.41; 95% CI, -0.64 to -0.18; p < 0.001) and aldosterone, without influencing serum creatinine (WMD, -3.64; 95% CI, -11.63 to 4.35; p = 0.37), glomerular filtration rate (SMD, 0.06; 95% CI, -0.13 to 0.25; p = 0.53), and adverse effects (RR, 0.95; 95% CI, 0.35 to 2.58; p = 0.93). In addition, N-/T-type CCB did not decrease the systolic blood pressure (BP) (WMD, 0.17; 95% CI, -1.05 to 1.39; p = 0.79) or diastolic BP (WMD, 0.64; 95% CI, -0.55 to 1.83; p = 0.29) when compared with L-type CCB. In CKD patients treated with RAS inhibitors, N-/T-type CCB is more effective than L-type CCB in reducing urine albumin/protein excretion without increased serum creatinine, decreased glomerular filtration rate, and increased adverse effects. The additional benefit is independent of BP and may be associated with decreased aldosterone (PROSPERO, CRD42020197560).

Clinical efficacy of supplementing qi dispelling wind and activating blood circulation method in the treatment of IgA nephropathy: A meta-analysis.

BACKGROUND: IgA nephropathy (IgAN) is a common primary glomerular disease, and supplementing qi dispelling wind and activating blood is commonly used as a treatment method in Chinese medicine. However, the existing studies have small sample sizes. This study aimed to use a meta-analysis to explore the clinical efficacy of this method and to systematically introduce this effective treatment. METHODS: We searched for randomized controlled trial studies on supplementing qi dispelling wind and activating blood circulation methods for IgAN indexed in the China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP, SinoMed, PubMed, EMBASE, and Web of Science databases, which were interrogated from database inception to January 2022. Combining the inclusion and exclusion criteria to screen the literature, we included a total of 15 eligible studies; the quality of the included studies was evaluated using the risk of bias assessment tool of the Cochrane System Revies Manual 5.4. The outcome indexes were extracted, and a meta-analysis was performed using Review Manager 5.4 software. RESULTS: Fifteen articles were included in this review. A meta-analysis of the results led to the conclusion that supplementing qi dispelling wind and activating blood circulation prescription has beneficial effects on the total effective rate [odds ratios = 3.95, 95% confidence interval (CI) 2.76-5.67], and can reduce 24-hour urinary protein quantity (mean deviation = -0.35, 95% CI -0.54 to -0.16) and serum creatinine (mean deviation = -15.41,95% CI -28.39 to -2.44) without impact normal level of alanine transaminase, hemoglobin, and serum albumin. CONCLUSIONS: Supplementing qi dispelling wind and activating blood can significantly improve renal function and reduce 24-hour urinary protein quantity levels in patients with IgAN compared to the use of non-Chinese medicine treatment. This finding provides a rationale for using this method in the clinical treatment of IgAN.

Effects of modified Huangqi Chifeng decoction on the IL-17 signaling pathway in an IgA nephropathy rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Immunoglobulin A nephropathy (IgAN) is an immune-related primary glomerular disease prevalent worldwide, with complicated clinical manifestations and an unclear pathogenesis. IgAN is the main cause of chronic renal failure and places a significant burden on patients and society. The modified Huangqi Chifeng decoction (MHCD) is an effective prescription for the clinical treatment of IgAN while its specific mechanism remains to be further elucidated. AIM OF THE STUDY: Based on the findings of previous network pharmacology-related method-based studies, this study aimed to further explore the mechanism of action of MHCD for IgAN treatment. MATERIALS AND METHODS: IgAN rat model was established by bovine serum protein + carbon tetrachloride + lipopolysaccharide. After successful modeling, the rats in the original model group were divided into 5 group: model group, telmisartan group, and MHCD high-, medium- and low-dose groups by random number table (n = 10 respectively). The corresponding drugs were applied for 8 weeks, and the experiment lasted for 21 weeks. At the end of the experiment, 24h urine protein quantification, serum biochemistry and IL-6 and IL-17A levels were measured. The pathological changes of kidney were observed by light microscope, immunofluorescence microscope and the changes of glomerular ultrastructure were observed by transmission electron microscope. The expression levels of IL-17 signaling pathway related proteins (HSP90, MMP9, NF-κB P65 and p-NF-κB P65) were detected by Western Blot and immunohistochemistry. RESULT: Telmisartan and MHCD treatment can reduce the 24h urinary protein level and improved blood stasis states of IgAN rats, alleviate the renal pathological injury, decrease the serum levels of IL-6, IL-17A and the expression levels of HSP90, MMP9 and p-NF-κB P65 related proteins in IL-17 signaling pathway. CONCLUSION: MHCD can down-regulate the expression of IL-17 signaling pathway-related factors in IgAN model rats, improve the state of blood stasis, and alleviate the pathological damage of kidney in rats.

Efficiency Analysis of Fuel Cell Components with Ionic Poly-Arylether Composite Membrane.

We use polyethylene glycol as an additive to explore how the hydrogen bonding of this additive changes the properties of SA8 blended sulfonated polyetheretherketone (SPEEK) composite films. We mixed a 5%wt polyethylene glycol solution into a 12.5%wt SA8 solution, and then prepared a film with a total weight of 40 g at a ratio of 1:99. The SA8 (PEG) solution was prepared and then mixed with 5%wt SPEEK solution, and a film-forming solution with a total weight of 8g in different mixing ratios was created. Polyethylene glycol (PEG) was mixed into the sulfonated polyarylether polymer SA8 to form physical cross-linking. Therefore, the sulfonated polyether ether ketone SPEEK was mixed in, and it exhibited good thermal stability and dimensional stability. However, there was some decrease in proton conductivity as the proportion of SPEEK increased. Although SPEEK mixed with sulfonated polymer reduces the proton conductivity, the physical cross-linking of PEG can improve the proton conductivity of the composite membrane, and adding SPEEK can not only solve the problem of the high sulfonation film swelling phenomenon, it can also improve the dimensional stability of the film through the hydrogen bonding force of PEG and obtain a composite film with excellent properties.

Traditional Chinese medicine compounds ameliorating glomerular diseases via autophagy: A mechanism review.

Glomerular diseases are major components of kidney disease, mainly manifested as podocyte disease, immune complex-associated glomerulonephritis, and renal autoimmune disease. They are the third leading cause of end-stage renal disease, especially in younger populations. Podocyte death or shedding is a key factor in the progression of glomerular diseases, and autophagy plays an important role in maintaining podocyte homeostasis. Dysfunction of autophagy has been associated with the progression of various glomerular diseases. Modulation of autophagy has been shown to play a protective role in experimental models of glomerular diseases, suggesting that autophagy is a potential therapeutic target for glomerular diseases. Traditional Chinese medicine (TCM) has unique advantages in the treatment of kidney disease. In vivo and in vitro studies have shown that TCM compounds can reduce podocyte apoptosis, inhibit inflammation, improve endoplasmic reticulum stress and oxidative stress responses, and play an active role via autophagy. This review summarizes the roles of autophagy in glomerular diseases and provides evidence that TCM compounds can regulate autophagy through different signaling pathways to ameliorate glomerular diseases.

Electric Field-Assisted Filling of Sulfonated Polymers in ePTFE Backing Material for Fuel Cell.

This study fabricated a composite ePTFE-backed proton-exchange membrane by filling the pores on the ePTFE backing with sulfonated polyarylene ethers through an externally supplied electric field. The morphology changes were observed under an SEM. The results suggested that the application of an electric field had led to the effective filling of pores by polymers. In addition, the composite membrane featured good dimensional stability and swelling ratio, and its water uptake, proton conductivity and component efficiency increased with voltage. It is found in this study that the external application of an electric field resulted in the effective filling of pores in the ePTFE by sulfonated polyarylene ether polymers and, thus, an improved composite membrane performance.

Ionomer Membranes Produced from Hexaarylbenzene-Based Partially Fluorinated Poly(arylene ether) Blends for Proton Exchange Membrane Fuel Cells.

In this study, a series of high molecular weight ionomers of hexaarylbenzene- and fluorene-based poly(arylene ether)s were synthesized conveniently through condensation and post-sulfonation modification. The use a of blending method might increase the stacking density of chains and affect the formation both of interchain and intrachain proton transfer clusters. Multiscale phase separation caused by the dissolution and compatibility differences of blend ionomer in high-boiling-point solvents was examined through analysis and simulations. The blend membranes produced in this study exhibited a high proton conductivity of 206.4 mS cm−1 at 80 °C (increased from 182.6 mS cm−1 for precursor membranes), excellent thermal resistance (decomposition temperature > 200 °C), and suitable mechanical properties with a tensile strength of 73.8−77.4 MPa. As a proton exchange membrane for fuel cell applications, it exhibits an excellent power efficiency of approximately 1.3 W cm−2. Thus, the ionomer membranes have strong potential for use in proton exchange membrane fuel cells and other electrochemical applications.

Efficacy and safety of drug-coated balloon in the treatment of acute myocardial infarction: a meta-analysis of randomized controlled trials.

Acute myocardial infarction (AMI) is one of the main causes of death in the world, and the incidence of AMI is increasing in the young population. Drug-coated balloon (DCB) has become an effective concept for the treatment of in-stent restenosis, small vessel disease, bifurcation lesions, high blood risk conditions, and even de novo large vessel disease. To ensure whether DCB can play an alternative role in AMI, we conducted a comprehensive meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of DCB in the treatment of AMI. Electronic databases were searched for RCTs that compared DCB with stent for AMI. The primary outcome was major adverse cardiac events (MACEs), the secondary outcome was late lumen loss (LLL). RevMan 5.3 software and RStudio software were used for data analysis. Five RCTs involving 528 patients with 6-12 months of follow-up were included. There was no significant difference in the incidence of MACEs between DCB group and stent group (RR, 0.85; 95% CI 0.42 to 1.74; P = 0.66). Lower LLL was shown in DCB group (WMD, - 0.29; 95% CI - 0.46 to - 0.12; P < 0.001). This meta-analysis of RCT showed that DCB might provide a promising way on AMI compared with stents. Rigorous patients' selection and adequate predilation of culprit lesions are necessary to optimize results and prevent bailout stent implantation.PROSPERO registration number: CRD42020214333.

Efficacy of Modified Huangqi Chifeng decoction in alleviating renal fibrosis in rats with IgA nephropathy by inhibiting the TGF-ß1/Smad3 signaling pathway through exosome regulation.

ETHNOPHARMACOLOGICAL RELEVANCE: IgA nephropathy is the most common form of primary glomerulonephritis and is a major cause of renal failure worldwide. Modified Huangqi Chifeng decoction (MHCD), a traditional Chinese herbal preparation, has clinical efficacy in reducing the 24-h urine protein levels in patients with IgA nephropathy. However, the molecular mechanism of MHCD needs further study. AIM OF THE STUDY: This study aimed to investigate the mechanisms by which MHCD treatment alleviates renal fibrosis. MATERIALS AND METHODS: An IgA nephropathy rat model was established using bovine serum albumin, carbon tetrachloride, and lipopolysaccharide. The rats were divided into control, model, telmisartan, low-dose MHCD, medium-dose MHCD, and high-dose MHCD groups. Treatments were administered to these groups for 8 weeks. Subsequently, the 24-h urine protein, serum creatinine, blood urea nitrogen, and blood albumin levels were measured. Pathological changes and degree of fibrosis in renal tissues were observed, and levels of the transforming growth factor-ß1 (TGF-ß1)/Smad3 signaling pathway components in renal tissues and TGF-ß1 in urinary exosomes were measured. RESULTS: Telmisartan and MHCD reduced 24-h urine protein levels, alleviated renal pathological injury, and decreased the renal expression of fibronectin, laminin, and collagen IV in rats with IgA nephropathy. Urinary exosomes were extracted and identified for further investigation of their role in renal fibrosis. MHCD reduced TGF-ß1 expression in urinary exosomes and reduced TGF-ß1 and p-Smad3 levels in renal tissues. CONCLUSION: MHCD alleviated renal fibrosis in rats with IgA nephropathy by inhibiting the TGF-ß1/Smad3 signaling pathway through the downregulation of TGF-ß1 expression in exosomes.

Analysis of Ferroptosis-Related Gene Expression and Prognostic Factors of Renal Clear Cell Carcinoma Based on TCGA Database.

INTRODUCTION: Renal clear cell carcinoma (ccRCC) is a common tumor of the urinary system, most of which are primary malignant tumors with high metastatic rate and remaining incurable. Ferroptosis is a newly discovered form of iron-dependent programmed cell necrosis in recent years, which is inextricably linked to the occurrence and development of tumors progression. Due to the complexity of the interaction between genes in ccRCC, the research on the pathogenesis of ccRCC is still not remarkably accurate. Therefore, whether ferroptosis-related genes (FRGs) can play a role in predicting prognosis in ccRCC needs to be discussed. METHODS: We entered the Cancer Genome Mapping Project (TCGA) database and downloaded the relevant genes and clinical research data of ccRCC patients. Lasso Cox regression was used to construct a multi-gene prognostic model in the TCGA cohort. R language software was used for drawing pictures related to our study. RESULTS: Most of the genes involved in ferroptosis (86.2%) existing differences between the tumor and normal tissues in the TCGA public gene database. In terms of univariate Cox regression analysis, 20 differentially expressed genes (DEGs) were associated with prognosis and survival (P<0.05). A prognostic model of 12 FRGs was constructed, and patients were segmented into two different groups depending on how risky they are. Considering overall survival, the high-risk group is dramatically lower than the low-risk group (P<0.001). In multivariate Cox regression analysis, risk scores and stage turned out be an independent prognostic factor (P<0.001). GO and KEGG analysis and ssGSEA analysis of DEGs revealed that these genes were related to immune-related pathways (P<0.05). CONCLUSION: This study established and identified the changes in FRGs expression and prognostic factors of ccRCC, which can be helpful for prognosis evaluation and clinical treatment of this disease.

Efficacy and safety of dual vs single renin-angiotensin-aldosterone system blockade in chronic kidney disease: An updated meta-analysis of randomized controlled trials.

BACKGROUND: To lower albuminuria and to achieve blood pressure (BP) goals, dual renin-angiotensin-aldosterone system (RAAS) inhibitors are sometimes used in clinical practice for the treatment of CKD. However, the efficacy and safety of dual RAAS blockade therapy remains controversial. METHODS: PubMed, EMBASE, and Cochrane Library were searched, and random effects model was used to calculate the effect sizes of eligible studies. Potential sources of heterogeneity were detected by meta-regression and subgroup analysis. RESULTS: The present meta-analysis of 72 randomized controlled trials with 10,296 patients demonstrated that dual RAAS blockade therapy was superior to monotherapy in reducing the urine albumin excretion, urine protein excretion, and BP. These beneficial effects were related to the decrease of glomerular filtration rate, the increase of serum potassium level, and higher rates of hyperkalemia and hypotension. Meanwhile, these effects did not lead to improvements in short-term or long-term outcomes, including doubling of serum creatinine, acute kidney injury, end-stage renal disease, mortality, and hospitalization. Compared with the single therapy, angiotensin-converting enzyme inhibitor (ACEI) in combination with angiotensin-receptor blocker (ARB) was a better dual therapy than ACEI or ARB in combination with renin inhibitor or aldosterone receptor antagonist in decreasing urine albumin excretion, urine protein excretion and BP, and the combination was not associated with a lower glomerular filtration rate. CONCLUSION: Compared with the single therapy, ACEI in combination with ARB was a better dual therapy than ACEI or ARB in combination with renin inhibitor or aldosterone receptor antagonist. Although ACEI in combination with ARB was associated with higher incidences of hyperkalemia and hypotension, careful individualized management and potassium binders may further expand its application (PROSPERO number CRD42020179398).