Exploring therapeutic mechanisms of Chuan Huang Fang-II in the treatment of acute kidney injury on chronic kidney disease patients from the perspective of lipidomics.

OBJECTIVE: This study aims to assess the clinical efficacy and safety of CHF-II in combination with RG for treating AKI on CKD (A on C), and to explore potential therapeutic mechanisms through lipidomics analysis. METHODS: 98 patients were enrolled and randomly assigned to the RG or RG + CHF groups. Both groups received RG therapy, with RG + CHF group additionally receiving CHF-II treatment over a duration of two weeks. Evaluation endpoints included changes in renal function, blood lipid profiles, urinary AKI biomarkers, and TCM symptoms before and after treatment. Serum samples were collected for lipid metabolite analysis. RESULTS: The total clinical effective rate in RG + CHF group was 73.5%, and that of RG group was 40.8%. TCM syndrome scores in RG + CHF group showed a more pronounced decrease (p < 0.05). Scr, BUN, and UA levels decreased while eGFR levels increased in both groups (p < 0.05), with a greater magnitude of change observed in the RG + CHF group. Urinary AKI biomarkers decreased more in RG + CHF group (p < 0.05). No serious adverse events occurred during the trial. 58 different lipid metabolites and 48 lipid biomarkers were identified. According to the KEGG database, the possible metabolic pathways involved triglyceride metabolic pathway and fat digestion and absorption metabolic pathways. CONCLUSION: CHF-II effectively alleviated kidney injury and improved TCM syndrome scores in patients with A on C. Lipid differential metabolites could serve as diagnostic indicators for AKI in patients with CKD. The possible metabolic pathways might be implicated in therapeutic action of CHF-II in the prevention and treatment of patients with A on C.

Uropathogenic Escherichia coli infection: innate immune disorder, bladder damage, and Tailin Fang II.

Background: Uropathogenic Escherichia coli (UPEC) activates innate immune response upon invading the urinary tract, whereas UPEC can also enter bladder epithelial cells (BECs) through interactions with fusiform vesicles on cell surfaces and subsequently escape from the vesicles into the cytoplasm to establish intracellular bacterial communities, finally evading the host immune system and leading to recurrent urinary tract infection (RUTI). Tailin Fang II (TLF-II) is a Chinese herbal formulation composed of botanicals that has been clinically proven to be effective in treating urinary tract infection (UTI). However, the underlying therapeutic mechanisms remain poorly understood. Methods: Network pharmacology analysis of TLF-II was conducted. Female Balb/C mice were transurethrally inoculated with UPEC CFT073 strain to establish the UTI mouse model. Levofloxacin was used as a positive control. Mice were randomly divided into four groups: negative control, UTI, TLF-II, and levofloxacin. Histopathological changes in bladder tissues were assessed by evaluating the bladder organ index and performing hematoxylin-eosin staining. The bacterial load in the bladder tissue and urine sample of mice was quantified. Activation of the TLR4-NF-κB pathway was investigated through immunohistochemistry and western blotting. The urinary levels of interleukin (IL)-1ß and IL-6 and urine leukocyte counts were monitored. We also determined the protein expressions of markers associated with fusiform vesicles, Rab27b and Galectin-3, and levels of the phosphate transporter protein SLC20A1. Subsequently, the co-localization of Rab27b and SLC20A1 with CFT073 was examined using confocal fluorescence microscopy. Results: Data of network pharmacology analysis suggested that TLF-II could against UTI through multiple targets and pathways associated with innate immunity and inflammation. Additionally, TLF-II significantly attenuated UPEC-induced bladder injury and reduced the bladder bacterial load. Meanwhile, TLF-II inhibited the expression of TLR4 and NF-κB on BECs and decreased the urine levels of IL-1ß and IL-6 and urine leukocyte counts. TLF-II reduced SLC20A1 and Galectin-3 expressions and increased Rab27b expression. The co-localization of SLC20A1 and Rab27b with CFT073 was significantly reduced in the TLF-II group. Conclusion: Collectively, innate immunity and bacterial escape from fusiform vesicles play important roles in UPEC-induced bladder infections. Our findings suggest that TLF-II combats UPEC-induced bladder infections by effectively mitigating bladder inflammation and preventing bacterial escape from fusiform vesicles into the cytoplasm. The findings suggest that TLF-II is a promising option for treating UTI and reducing its recurrence.

Tetramethylpyrazine attenuates renal tubular epithelial cell ferroptosis in contrast-induced nephropathy by inhibiting transferrin receptor and intracellular reactive oxygen species.

Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury (AKI). Recently, ferroptosis was reported to be crucial for AKI pathogenesis. Our previous studies indicated antioxidant tetramethylpyrazine (TMP) prevent CIN in vivo. However, whether ferroptosis is involved in TMP nephroprotective mechanism against CIN is unclear. In the present study, we investigated the role of renal tubular epithelial cell ferroptosis in TMP reno-protective effect against CIN and the molecular mechanisms by which TMP regulates ferroptosis. Classical contrast-medium, Iohexol, was used to construct CIN models in rats and HK-2 cells. Results showed that tubular cell injury was accompanied by ferroptosis both in vivo and in vitro, including the typical features of ferroptosis, Fe2+ accumulation, lipid peroxidation and decreased glutathione peroxidase 4 (GPX4). Ferroptosis inhibition by classic inhibitors Fer-1 and DFO promoted cell viability and reduced intracellular ROS production. Additionally, TMP significantly inhibited renal dysfunction, reduced AKI biomarkers, prevented ROS production, inhibited renal Fe2+ accumulation and increased GPX4 expression. Expressions of various proteins associated with iron ion metabolism, including transferrin receptor (TFRC), divalent metal transporter 1, iron-responsive element binding protein 2, ferritin heavy chain 1, ferroportin 1, and heat shock factor binding protein 1, were examined using mechanistic analyses. Among these, TFRC changes were the most significant after TMP pretreatment. Results of siRNA knockdown and plasmid overexpression of TFRC indicated that TFRC is essential for TMP to alleviate ferroptosis and reduce LDH release, Fe2+ accumulation and intracellular ROS. Our findings provide crucial insights about the potential of TMP in treating AKI associated with ferroptosis.

Elevation of serum human epididymis protein 4 (HE4) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as predicting factors for the occurrence of acute kidney injury on chronic kidney disease: a single-center retrospective self-control study.

Objectives: To evaluate whether novel biomarkers of renal injury, serum HE4 and NT-proBNP could predict acute kidney injury (AKI) on chronic kidney disease (CKD) (A on C) and assess the specificity and efficiency of serum creatinine (SCr), HE4 and NT-proBNP in identifying potential AKI. Meanwhile, the potential early-warning value of HE4 and NT-proBNP in CKD patients was explored. Methods: We performed a single-center, retrospective cohort study of 187 adult CKD patients. 32 AKI (grades 1-2) patients with pre-existing CKD (stages 3-5) were Group 1, 59 patients of CKD (stages 4-5) were Group 2. Another 96 patients of CKD (stages 1-3) were Group 3. All patients received general treatments, Group 1 patients received Chinese herb formulation (Chuan Huang Fang-Ⅱ, CHF-Ⅱ) simultaneously. These 155 CKD (stages 1-5) without AKI patients were observed for descriptive analysis. Results: HE4 in Group 1 (860.63 ± 385.40) was higher than that in Group 2 (673.86 ± 283.58) before treatments. BUN, SCr, UA, NGAL, IL18, HE4 and NT-proBNP in Group 1 were lower, while eGFR was higher (p < 0.01, after vs. before treatments). In Group 1, both HE4 and NT-proBNP were positively correlated with SCr (respectively r = 0.549, 0.464) before treatments. The diagnostic performance of serum HE4 and NT-proBNP for A on C was 351.5 pmol/L, 274.5 pg/mL as the optimal cutoff value Area Under Curve (AUC) 0.860 (95% CI: 0.808 - 0.913, p < 0.001), [AUC 0.775 (95% CI: 0.697 - 0.853, p < 0.001), with a sensitivity and specificity of 100% and 66.5%, 87.5% and 48.8%, respectively]. In Group 2, serum HE4 was correlated with SCr (r = 0.682, p < 0.01) before treatments. Serum HE4 and NT-proBNP were elevated in advanced CKD stages, and were increased as CKD stages progressed with statistical significance. Conclusion: This work indicated serum HE4 and NT-proBNP should elevate in A on C and CKD patients, HE4 is positively correlated with the disease severity, and patients with higher HE4 and NT-proBNP usually have poorer prognosis. Thus, serum HE4 and NT-proBNP are impactful predictors of A on C. Additionally, serum HE4 and NT-proBNP have the potential to evaluate clinical efficacy of A on C.

Synthesis of Mesoporous and Hollow SiO2@ Eu(TTA)3phen with Enhanced Fluorescence Properties.

Lanthanide ions are extensively utilized in optoelectronic materials, owing to their narrow emission bandwidth, prolonged lifetime, and elevated fluorescence quantum yield. Inorganic non-metallic materials commonly serve as host matrices for lanthanide complexes, posing noteworthy challenges regarding loading quantity and fluorescence performance stability post-loading. In this investigation, an enhanced Stöber method was employed to synthesize mesoporous hollow silica, and diverse forms of SiO2@Eu(TTA)3phen (S@Eu) were successfully prepared. Transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), Fourier-transform infrared (FTIR) spectroscopy, and X-ray photoelectron spectroscopy (XPS) outcomes revealed the effective binding of silica with Eu(TTA)3phen through both physical adsorption and chemical bonding. This includes the formation of Si-O-C bonds between silica and the ligand, as well as Si-O-Eu bonds between silica and europium ions. Fluorescence tests demonstrated that the mesoporous SiO2@Eu(TTA)3phen(MS@Eu) composite exhibited the highest fluorescence intensity among the three structured silica composites, with a notable enhancement of 46.60% compared to the normal SiO2@Eu(TTA)3phen composite. The Brunauer-Emmett-Teller (BET) analysis indicated that the specific surface area plays a crucial role in influencing the fluorescence intensity of SiO2@Eu(TTA)3phen, whereby the prepared mesoporous hollow silica further elevated the fluorescence intensity by 61.49%. Moreover, SiO2@Eu(TTA)3phen demonstrated 11.11% greater cyclic stability, heightened thermal stability, and enhanced alkaline resistance relative to SiO2@Eu(TTA)3phen.

Bibliometric and visualization analysis of kidney repair associated with acute kidney injury from 2002 to 2022.

Background: Renal repair is closely related to the prognosis of acute kidney injury (AKI) and has attracted increasing attention in the research field. However, there is a lack of a comprehensive bibliometric analysis in this research area. This study aims at exploring the current status and hotspots of renal repair research in AKI from the perspective of bibliometrics. Methods: Studies published between 2002 and 2022 related to kidney repair after AKI were collected from Web of Science core collection (WoSCC) database. Bibliometric measurement and knowledge graph analysis to predict the latest research trends in the field were performed using bibliometrics software CiteSpace and VOSviewer. Results: The number of documents related to kidney repair after AKI has steadily increased over 20 years. The United States and China contribute more than 60% of documents and are the main drivers of research in this field. Harvard University is the most active academic institution that contributes the most documents. Humphreys BD and Bonventre JV are the most prolific authors and co-cited authors in the field. The American Journal of Physiology-Renal Physiology and Journal of the American Society of Nephrology are the most popular journals in the field with the greatest number of documents. "exosome", "macrophage polarization", "fibroblast", and" aki-ckd transition" are high-frequency keywords in this field in recent years. Extracellular vesicles (including exosomes), macrophage polarization, cell cycle arrest, hippo pathway, and sox9 are current research hotspots and potential targets in this field. Conclusion: This is the first comprehensive bibliometric study on the knowledge structure and development trend of AKI-related renal repair research in recent years. The results of the study comprehensively summarize and identify research frontiers in AKI-related renal repair.

Nephroprotective mechanisms of Rhizoma Chuanxiong and Radix et Rhizoma Rhei against acute renal injury and renal fibrosis based on network pharmacology and experimental validation.

The molecular mechanisms of Rhizoma Chuanxiong (Chuanxiong, CX) and Rhei Radix et Rhizoma (Dahuang, DH) in treating acute kidney injury (AKI) and subsequent renal fibrosis (RF) were investigated in this study by applying network pharmacology and experimental validation. The results showed that aloe-emodin, (-)-catechin, beta-sitosterol, and folic acid were the core active ingredients, and TP53, AKT1, CSF1R, and TGFBR1 were the core target genes. Enrichment analyses showed that the key signaling pathways were the MAPK and IL-17 signaling pathways. In vivo experiments confirmed that Chuanxiong and Dahuang pretreatments significantly inhibited the levels of SCr, BUN, UNAG, and UGGT in contrast media-induced acute kidney injury (CIAKI) rats (p < 0.001). The results of Western blotting showed that compared with the control group, the protein levels of p-p38/p38 MAPK, p53, and Bax in the contrast media-induced acute kidney injury group were significantly increased, and the levels of Bcl-2 were significantly reduced (p < 0.001). Chuanxiong and Dahuang interventions significantly reversed the expression levels of these proteins (p < 0.01). The localization and quantification of p-p53 expression in immunohistochemistry technology also support the aforementioned results. In conclusion, our data also suggest that Chuanxiong and Dahuang may inhibit tubular epithelial cell apoptosis and improve acute kidney injury and renal fibrosis by inhibiting p38 MAPK/p53 signaling.

Potential therapeutic effects of Chinese meteria medica in mitigating drug-induced acute kidney injury.

Drug-induced acute kidney injury (DI-AKI) is one of the leading causes of kidney injury, is associated with high mortality and morbidity, and limits the clinical use of certain therapeutic or diagnostic agents, such as antineoplastic drugs, antibiotics, immunosuppressants, non-steroidal anti-inflammatory drugs, and contrast media. In recent years, numerous studies have shown that many Chinese meteria medica, metabolites derived from botanical drugs, and Chinese medicinal formulas confer protective effects against DI-AKI by targeting a variety of cellular or molecular mechanisms, such as oxidative stress, inflammatory, cell necrosis, apoptosis, and autophagy. This review summarizes the research status of common DI-AKI with Chinese meteria medica interventions, including cisplatin, gentamicin, contrast agents, methotrexate, and acetaminophen. At the same time, this review introduces the metabolites with application prospects represented by ginseng saponins, tetramethylpyrazine, panax notoginseng saponins, and curcumin. Overall, this review provides a reference for the development of promising nephroprotectants.

Chuan Huang Fang combining reduced glutathione in treating acute kidney injury (grades 1-2) on chronic kidney disease (stages 2-4): A multicenter randomized controlled clinical trial.

Lack of effective drugs for acute kidney injury (AKI) grades 1-2 is a crucial challenge in clinic. Our previously single-center clinical studies indicated Chuan Huang Fang (CHF) might have nephroprotection in AKI on chronic kidney disease (CKD) (A on C) patients by preventing oxidant damage and inhibiting inflammation. Reduced glutathione (RG) has recently been shown to increase the clinical effectiveness of high-flux hemodialysis among patients with severe AKI. In this multicenter randomized controlled clinical study, we designed a new protocol to assess the efficacy and safety of CHF combining RG in patients with A on C. We also explored therapeutic mechanisms from renal fibrosis biomarkers. 98 participants were randomly and equally divided into the RG and RG + CHF subgroups. The RG and RG + CHF groups received general treatments with RG and a combination of RG and CHF, respectively. The therapy lasted for 2 weeks. In this study, the primary assessment result was a difference in the slope of serum creatinine (Scr) over the course of 2 weeks. The secondary evaluation outcomes were alterations in blood urea nitrogen (BUN), uric acid (UA), estimated glomerular filtration rate (eGFR), urinary AKI biomarkers, renal fibrosis biomarkers (transforming growth factor-ß 1 (TGF-ß 1), connective tissue growth factor (CTGF)), and traditional Chinese medicine (TCM) symptoms. Furthermore, vital signs and adverse events (AEs) were observed. Both groups had a slower renal function decline after treatment than before treatment. Compared with RG group, more reductions of Scr, BUN, UA, and better improvement of eGFR were observed in RG + CHF group (p < 0.05). Additionally, the levels of urinary AKI biomarkers, renal fibrosis biomarkers, and TCM syndromes were decreased in RG + CHF group versus RG group (p < 0.05). No significant between-group differences were observed of AEs. We thus concluded this novel therapy of CHF combining RG might be a useful method for treating A on C patients.

Efficacy and safety of tailin formulation combined with continuous low-dose antibiotic therapy in patients with recurrent urinary tract infection: A multicenter, randomized, controlled clinical trial.

Persistent inflammation associated with recurrent urinary tract infection (rUTI) is a crucial inducement of inflammation-driven renal fibrosis (IDRF). Although continuous low-dose antibiotic therapy (CLAT) is the common treatment for rUTI, its clinical efficacy remains unsatisfactory. Tailin formulation (TLF), a Chinese herbal formulation prescribed for treating rUTI, is effective in alleviating symptoms and reducing recurrence. This study was to evaluate the efficacy and safety of TLF combined with CLAT compared with CLAT used alone in patients with rUTI. In this multicenter, randomized, controlled clinical trial, patients were assigned (1:1) to receive either TLF + CLAT or CLAT for 12 weeks. The primary outcome was the effective rate at week 12 of the treatment. The secondary outcomes were the recurrent rate at week 4 and week 12 post treatment; the post-treatment changes in renal tubular injury markers (urinary N-acetyl-ß-d-glucosaminidase (NAG) and ß2-microglobulin (ß2-MG)), profibrotic factors (urinary monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor beta1 (TGF-ß1)), and traditional Chinese medicine (TCM) symptoms, and vital signs indicators and serious adverse events (SAEs) were also monitored throughout the trial. A total of 195 patients were included in the final analysis. The TLF + CLAT group had a higher effective rate and a lower recurrence rate than the CLAT group (p < 0.01). Significant decrease of urinary NAG and ß2-MG was observed in the TLF + CLAT group vs. CLAT group (p < 0.01), and similar changes were observed in profibrotic factors (urinary MCP-1 and TGF-ß1) (p < 0.05), which indicated that TLF might have potential renal tubular protection and anti-fibrosis effects. Additionally, a positive correlation within a certain range was shown in the correlation analysis of medical history (months) of rUTI patients with urinary MCP-1 (r = 0.50, p < 0.05) and TGF-ß1 (r = 0.78, p < 0.01). A significant difference was also observed in TCM symptoms (p < 0.01). There were no obvious adverse reactions that occurred during this study. We conclude that TLF combined with CLAT was superior to CLAT used alone in reducing rUTI recurrence, alleviating the non-infection-related physical symptoms and protecting renal tubular and anti-fibrosis, which suggests this novel therapy might be an available treatment with great promise in treating rUTI.

Excellent Photonic and Mechanical Properties of Macromorphic Fibers Formed by Eu3+-Complex-Anchored, Unzipped, Multiwalled Carbon Nanotubes.

The macromorphic properties of carbon nanotubes perform poorly because of their size limitations: nanosize in diameters and microsize in length. In this work, to realize these dual purposes, we first used an electrochemical method to tear the surface of multiwalled carbon nanotubes (MWCNTs) to anchor photonic Eu3+-complexes there. Through the polar reactive groups endowed by the tearing, the Eu3+-complexes coordinate at the defected structures, obtaining the Eu3+-complex-anchored, unzipped, multiwalled carbon nanotubes (E-uMWCNTs). The controllable surface-breaking retains the MWCNTs' original, excellent mechanical properties. Then, to obtain the macromorphic structure with infinitely long fibers, a wet-spinning process was applied via the binding of a small quantity of polyvinyl alcohol (PVA). Thus, the wet-spun fibers with high contents of E-uMWCNTs (E-uMWCNT-Fs) were produced, in which the E-uMWCNTs took 33.3 wt%, a high ratio in E-uMWCNT-Fs. On the other hand, due to the reinforcing effect of E-uMWCNTs, the highest tensile strength can reach 228.2 MPa for E-uMWCNT-Fs. Meanwhile, the E-uMWCNT-Fs show high-efficiency photoluminescence and excellent media resistance performance due to the embedding effect of PVA on the E-uMWCNTs. Therefore, E-uMWCNT-Fs can exhibit excellent luminescence properties in aqueous solutions at pH 4~12 and in some high-concentration metal-ion solutions. Those distinguished performances promise outstanding innovations of this work.

Synthesis, modification and application of titanium dioxide nanoparticles: a review.

Titanium dioxide (TiO2) has been heavily investigated owing to its low cost, benign nature and strong photocatalytic ability. Thus, TiO2 has broad applications including photocatalysts, Li-ion batteries, solar cells, medical research and so on. However, the performance of TiO2 is not satisfactory due to many factors such as the broad band gap (3.01 to 3.2 eV) and fast recombination of electron-hole pairs (10-12 to 10-11 s). Plenty of work has been undertaken to improve the properties, such as structural and dopant modifications, which broaden the applications of TiO2. This review mainly discusses the aspects of TiO2-modified nanoparticles including synthetic methods, modifications and applications.

Efficacy and Safety of Chuan Huang Fang Combining Reduced Glutathione in Treating Acute Kidney Injury (Grades 1-2) on Chronic Kidney Disease (Stages 2-4): Study Protocol for a Multicenter Randomized Controlled Clinical Trial.

Background: Acute kidney injury (AKI) is a global public health challenge resulting in considerable morbidity and mortality. AKI on chronic kidney disease (CKD) (AKI on CKD, A on C) accounts for about a third of total AKI. For severe AKI grade 3, renal replacement therapy (RRT) should be implemented in time. However, the lack of recognized drug treatment method for AKI grades 1-2 is a crucial problem in clinic. Chuan Huang Fang (CHF) is a Chinese herbal formulation developed for the treatment of A on C from the Shanghai Municipal Hospital of Traditional Chinese Medicine. Our previous studies suggested that CHF might effectively protect renal functions of A on C patients. As a widely used antioxidant in clinic, reduced glutathione (RG) is reported to improve the clinical efficacy of high-flux hemodialysis (HFHD) in severe AKI patients recently. To address the crucial problem mentioned above, thus we design a new clinical protocol of CHF combining RG and try to evaluate the efficacy and safety of this protocol in treating patients diagnosed with CKD stages 2-4 complicated with AKI grades 1-2. Methods: This is a multicenter randomized controlled clinical trial. We intend to enroll 162 participants, and these participants will be divided into the RG group, the CHF group, and the RG + CHF group randomly assigning 1 : 1 : 1 principle. The RG group will be general treatments combining RG, the CHF group will be general treatments combining CHF, and the RG + CHF group will be general treatments combining RG and CHF. The duration of treatment will last two weeks. The primary evaluation outcome will be the change in the slope of serum creatinine (Scr) over 2 weeks. Secondary evaluation outcomes include changes in blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), urinary AKI biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), gamma-glutamyl transpeptidase (γ-GT), etc.), traditional Chinese medicine (TCM) symptoms, inflammatory indicators, and oxidative stress indicators. Meanwhile, the vital sign indicators and adverse events (AEs) will be closely observed. These dates will be meticulously recorded and properly handled by investigators throughout the study. Discussion. This study will provide convictive research-derived data to evaluate clinical efficacy and safety of CHF combing RG for CKD stages 2-4 complicated with AKI grades 1-2 and provide an evidence-based recommendation for clinicians. The timely completion of this trial will provide a novel drug treatment method for A on C. This trial is registered with ChiCTR2100043311 and registered on February 9, 2021.

Tetramethylpyrazine: An Active Ingredient of Chinese Herbal Medicine With Therapeutic Potential in Acute Kidney Injury and Renal Fibrosis.

As an increasing public health concern worldwide, acute kidney injury (AKI) is characterized by rapid deterioration of kidney function. Although continuous renal replacement therapy (CRRT) could be used to treat severe AKI, effective drug treatment methods for AKI are largely lacking. Tetramethylpyrazine (TMP) is an active ingredient of Chinese herb Ligusticum wallichii (Chuan Xiong) with antioxidant and anti-inflammatory functions. In recent years, more and more clinical and experimental studies suggest that TMP might effectively prevent AKI. The present article reviews the potential mechanisms of TMP against AKI. Through search and review, a total of 23 studies were finally included. Our results indicate that the undergoing mechanisms of TMP preventing AKI are mainly related to reducing oxidative stress injury, inhibiting inflammation, preventing apoptosis of intrinsic renal cells, and regulating autophagy. Meanwhile, given that AKI and chronic kidney disease (CKD) are very tightly linked by each other, and AKI is also an important inducement of CKD, we thus summarized the potential of TMP impeding the progression of CKD through anti-renal fibrosis.

Clinical efficacy of Tailin formulation combined with continuous low-dose antimicrobial therapy for recurrent urinary tract infection: study protocol for a multicenter, double-blind, randomized, controlled clinical trial.

BACKGROUND: Given the increasing rates of antimicrobial resistance (AMR), recurrent urinary tract infection (rUTI) is becoming refractory more and more. Antibiotic prophylaxis including continuous low-dose antibiotic therapy (CLAT), is the common treatment for rUTI of the world. However, the presumably adverse reactions caused by CLAT alone should be paid more attention. Studies indicated that Chinese herbal medicine (CHM) might be an available treatment method for rUTI. Tailin formulation (TLF) is a herbal prescription developed for the treatment of rUTI in the 2000s in Shanghai Municipal Hospital of Traditional Chinese Medicine. Our previous studies have shown TLF could prevent urinary tract infection both in pyelonephritis (PN) rat model and in PN patients. Additionally, our published data demonstrated TLF is helpful to reduce the recurrence of rUTI and protect renal tubular function in clinic. In order to find a novel treating project for rUTI to increase the clinical curative effect, we thus try to combine TLF with CLAT to treat rUTI and design an optimized, pragmatically clinical trial to evaluate the efficacy and safety of this project. METHODS/DESIGN: This is a multicenter, double-blind, randomized, controlled clinical trial. We will enroll 200 eligible patients diagnosed with uncomplicated rUTI and then divide them randomly into two groups with a 1:1 ratio: TLF + CLAT group and placebo + CLAT group. This trial consists of two stages, a 12-week period of treatment and a 12-week period of post-treatment follow-up, respectively. The primary outcome will be the recurrence rate at the 12th week of the follow-up period; the second outcomes will be the post-treatment changes in renal and liver function; furthermore, traditional Chinese medicine (TCM) symptoms, non-infection-related physical signs, and subjective symptoms will be scored, and the number of episodes of each subject will be also recorded; meanwhile, vital signs indicators and serious adverse events (SAEs) will be monitored throughout the trial. DISCUSSION: This study will provide convictive research-derived data to evaluate clinical efficacy and safety of TLF combined with CLAT for rUTI, and provide an evidence-based recommendation for clinicians. Moreover, post-treatment changes in non-infection-related physical signs and subjective symptoms were included in the efficacy evaluation, which is important and more significant for assessing the clinical benefits for those rUTI patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100041914 . Registered on 10 January 2021. Protocol date and version: September 12, 2020; version 1.

Two-Dimensional Transition Metal Oxide and Hydroxide-Based Hierarchical Architectures for Advanced Supercapacitor Materials.

The supercapacitor has been widely seen as one of the most promising emerging energy storage devices, by which electricity is converted from chemical energy and stored. Two-dimensional (2D) metal oxides/hydroxides (TMOs/TMHs) are revolutionizing the design of high-performance supercapacitors because of their high theoretical specific capacitance, abundance of electrochemically active sites, and feasibility for assembly in hierarchical structures by integrating with graphitic carbon, conductive polymers, and so on. The hierarchical structures achieved can not only overcome the limitations of using a single material but also bring new breakthroughs in performance. In this article, the research progress on 2D TMOs/TMHs and their use in hierarchical structures as supercapacitor materials are reviewed, including the evolution of supercapacitor materials, the configurations of hierarchical structures, the electrical properties regulated, and the existence of advantages and drawbacks. Finally, a perspective covering directions and challenges related to the development of supercapacitor materials is provided.

Immunosuppressive agents in the treatment of IgA nephropathy: A meta-analysis of clinical randomized controlled literature.

IgA nephropathy (IgAN) is the most common form of glomerulonephritis in the world. Immunosuppressive therapy has been widely used in IgAN patients at home and abroad. The present meta-analysis aimed to assess the efficacy and safety of different immunosuppressive agents in patients with biopsy proven IgAN, in order to provide guidance for the clinical treatment of IgAN treatment options. We conducted a meta-analysis of the published randomized controlled trials (RCTs). PubMed, EMBASE, Web of Science, Cochrane Library, Medline, WanFang, Weipu, and CNKI were searched for relevant RCTs published between 2000 and December 2017. Data were analyzed with the random effects model using Review Manager5.3 to evaluate the effect of immunosuppressive agents on IgAN. 52 RCTs were involving 2,930 patients were included in the review. Compared with steroids, immunosuppressive agents, including acetazolamide (AZA) [complete response (CR)/partial response (PR); relative risk (RR), 5.92; 95% confidence interval (CI) 3.07-11.44; P< 0.00001], leflunomide (LEF) (CR/PR; RR, 1.63; 95% CI,1.22-2.17; P = 0.0008), mycophenolate mofetil (MMF) (CR/PR; RR, 1.59; 95%CI, 1.02-2.49; P = 0.04), cyclophosphamide (CTX) (CR/PR; RR, 3.39; 95%CI, 1.03-11.14; P = 0.04), and Tacrolimus (TAC) (CR/PR; RR, 1.72; 95%CI, 0.99-2.96; P = 0.05) resulted in increased partial or complete proteinuria remission. There was no significant difference in the total effective rate between MMF and Placebo (CR/PR; RR, 0.92; 95% CI, 0.33-2.56; P = 0.87). Compared with CTX, MMF showed higher effectiveness (CR/PR; RR, 3.32; 95% CI, 1.83-6.01; P< 0.0001) and LEF showed higher effectiveness (CR/PR; RR, 1.85; 95% CI, 1.17C-2.92; P = 0.009) with a lower incidence of adverse events. The results showed that immunosuppressive agents are a promising strategy and should be investigated further. MMF is the safest, the best therapeutic result and the least side effects than the other immunosuppressive agents.

Fluorescent SiO2@Tb3+(PET-TEG)3Phen Hybrids as Nucleating Additive for Enhancement of Crystallinity of PET.

A hybrid polymer of SiO2@Tb3+(poly(ethylene terephthalate)-tetraglycol)3 phenanthroline (SiO2@Tb3+(PET-TEG)3Phen) was synthesized by mixing of inorganic SiO2 nanoparticles with polymeric segments of PET-TEG, whereas PET-TEG was achieved through multi-step functionalization strategy. Tb3+ ions and ß-diketonate ligand Phen were added in resulting material. The experimental results demonstrated that it was well blended with PET as a robust additive, and not only promoted the crystallinity, but also possessed excellent luminescence properties. An investigation of the mechanism revealed that the SiO2 nanoparticles functioned as a crystallization promotor; the Tb3+ acted as the fluorescent centre; and the PET-TEG segments played the role of linker and buffer, providing better compatibility of PET matrix with the inorganic component. This work demonstrated that hybrid polymers are appealing as multifunctional additives in the polymer processing and polymer luminescence field.

Chinese Medicine Might Be A Promising Way for A Solution to Arsenic Nephrotoxicity.

Arsenic from environmental contamination is a risk factor for kidney disease, and the clinical use of arsenic also triggers a new concern that the potential kidney damage caused by exposure to clinical doses of arsenic trivalent. So far, the undergoing mechanisms contributing to arsenic nephrotoxicity mostly remain unclear, and universally accepted methods for preventing this complication are limited too. Ancient Chinese medical scientists recognized the toxicity of arsenic long ago, and there were some records of Chinese herbs against arsenic poisoning in ancient books of Chinese medicine. In the past decade, several herbal formulations, as well as some potentially active compounds extracted from Chinese herbs, have been employed to prevent arsenic nephrotoxicity both in vivo and in vitro and showed better therapeutic effects. The present paper thus summarizes and discusses these Chinese medicine methods in preventing such a public health problem. In addition, we call for large, well-designed, randomized, and controlled clinical trials to be performed to further assess the efficacy and safety of these potential methods of Chinese medicine against arsenic nephrotoxicity.

Building Oxime-Ni2+ Complex on Polymeric Carbon Nitride: Molecular-Level Design of Highly Efficient Hydrogen Generation Photocatalysts.

We report an effective strategy to in situ construct the oxime-Ni2+ complex unit on polymeric carbon nitride (PCN) as a molecular catalyst for the highly efficient hydrogen evolution reaction (HER). The PCN was functionalized with oxime groups that allowed for immobilizing Ni2+ to form oxime-Ni2+ complex units on the PCN surface with uniform distribution. The electrochemical characterizations reveal that these oxime-Ni2+ units can effectively capture photogenerated electrons from PCN and serve as active catalytic sites for proton reduction. Notably, the oxime-Ni2+ enriched PCN showed even higher activities for photocatalytic hydrogen evolution than the Pt-loaded PCN. This work provides a new way to synthesize low-cost photocatalysts with surface grafting of noble-metal-free molecular HER catalysts for efficient light-driven hydrogen generation.