Huanglian Decoction treats Henoch-Schonlein purpura nephritis by inhibiting NF-κB/NLRP3 signaling pathway and reducing renal IgA deposition.

Henoch-Schonlein purpura nephritis (HSPN) is a systemic vascular inflammatory disease. Huanglian Decoction (HLD) ameliorates renal injury in nephritis; however, the mechanism of action of HLD on HSPN has not been investigated. This study aimed to investigate the protective mechanism of HLD treatment in HSPN. The effects of HLD on HSPN biochemical indices, kidney injury and NF-κB/NLRP3 signaling pathway were analyzed by biochemical analysis, ELISA, HE and PAS staining, immunohistochemistry, immunofluorescence, and Western Blot. In addition, the effects of HLD on HSPN cells were analyzed. We found that HLD treatment significantly reduced renal tissue damage, decreased the levels of IL-17, IL-18, TNF-α, and IL-1ß, and increased the levels of TP and ALB in HSPN mice. It also inhibited the deposition of IgA, IgG, and C3 in kidney tissues and significantly decreased the expression of IκBα, p-IκBα, NLRP3, caspase-1, and IL-1ß in kidney tissues and cells. In addition, PMA treatment inhibited the above-mentioned effects of HLD. These results suggested that HLD attenuates renal injury, IgA deposition, and inflammation in HSPN mice and its mechanism of action may be related to the inhibition of the NF-κB/NLRP3 pathway.

Piezoelectric hydrogel for treatment of periodontitis through bioenergetic activation.

The impaired differentiation ability of resident cells and disordered immune microenvironment in periodontitis pose a huge challenge for bone regeneration. Herein, we construct a piezoelectric hydrogel to rescue the impaired osteogenic capability and rebuild the regenerative immune microenvironment through bioenergetic activation. Under local mechanical stress, the piezoelectric hydrogel generated piezopotential that initiates osteogenic differentiation of inflammatory periodontal ligament stem cells (PDLSCs) via modulating energy metabolism and promoting adenosine triphosphate (ATP) synthesis. Moreover, it also reshapes an anti-inflammatory and pro-regenerative niche through switching M1 macrophages to the M2 phenotype. The synergy of tilapia gelatin and piezoelectric stimulation enhances in situ regeneration in periodontal inflammatory defects of rats. These findings pave a new pathway for treating periodontitis and other immune-related bone defects through piezoelectric stimulation-enabled energy metabolism modulation and immunomodulation.

Bismuth nanoclusters on nitrogen-doped porous carbon nanoenzyme for cancer therapy.

Among the emerging cancer therapeutic methods, nanocatalytic therapy through the rational design of nanozymes is considered to be a promising strategy. However, high-performance nanozymes with the ability to catalyze the production of toxic substances to efficiently kill cancer cells are still highly desired. Herein, we fabricate bismuth nanoclusters loaded on nitrogen-doped porous carbon (Bi-NC) as a nanozyme for cancer therapy. The Bi-NC nanozyme displays both peroxidase (POD) and glutathione oxidase (GSHOx) biomimetic enzymatic activities, especially in a tumor microenvironment (TME), which catalyzes the production of hydroxyl radicals (·OH) and depletes antioxidant glutathione (GSH), simultaneously. Moreover, Bi-NC exhibits good photothermal conversion performance under near-infrared light irradiation. After surface modification with hyaluronic acid (HA) to improve the dispersity of nanoparticles and their accumulation in tumor tissues, Bi-NC@HA exhibits remarkable antitumor effects through the synergistic effect of catalytic and photothermal therapy. This work provides a new pathway for designing high-performance nanozymes for cancer catalytic therapy.

Active colorimetric bilayer polycaprolactone-eucalyptus oil@silk fibroin-bayberry anthocyanins (PCL-EO@SF-BAs) membrane with directional water transport (DWT) for food packaging.

Currently, designing smart membranes with multifunctional effectiveness is crucial to food freshness monitoring and retention. Herein, an active colorimetric Janus bilayer membrane with directional water transport (DWT) performance is constructed by electrospinning, which comprises a hydrophilic layer of silk fibroin-bayberry anthocyanins (SF-BAs) and a hydrophobic layer of polycaprolactone-eucalyptus oil (PCL-EO). The entities of BAs and EO are well dispersed in the fiber matrix by hydrogen bonds and physical interactions, respectively. BAs endow the membrane colorimetric response and antioxidant activity, and EO contributes to the antibacterial activity while DWT performance is generated from the asymmetric wettability of the two layers. The bilayer membrane has an accumulative one-way transport index of 1077%, an overall moisture management capacity of 0.76 and a water evaporation rate of 0.48 g h-1. Moreover, the release of BAs and EO was predominantly controlled by Fickian diffusion. As a pH-sensing indicator, PCL-EO@SF-BAs is highly sensitive to external pH stimuli and the response is reversible. In addition to freshness monitoring, PCL-EO@SF-BAs can extend the shelf-life of pork beyond 100% at 4 °C. Also, it can extend the shelf life of shrimp by approximately 70% at 25 °C with the synergistic effect of antibacterial activity and the DWT performance.

Exposure to herbicides mixtures in relation to type 2 diabetes mellitus among Chinese rural population: Results from different statistical models.

BACKGROUND: Although it has been reported that herbicides exposure is related to adverse outcomes, available evidence on the associations of quantitatively measured herbicides with type 2 diabetes mellitus (T2DM) and prediabetes is still scant. Furthermore, the effects of herbicides mixtures on T2DM and prediabetes remain unclear among the Chinese rural population. AIMS: To assess the associations of plasma herbicides with T2DM and prediabetes among the Chinese rural population. METHODS: A total of 2626 participants were enrolled from the Henan Rural Cohort Study. Plasma herbicides were measured with gas chromatography coupled to triple quadrupole tandem mass spectrometry. Generalized linear regression analysis was employed to assess the associations of a single herbicide with T2DM, prediabetes, as well as indicators of glucose metabolism. In addition, the quantile g-computation and environmental risk score (ERS) structured by adaptive elastic net (AENET), and Bayesian kernel machine regression (BKMR) were used to estimate the effects of herbicides mixtures on T2DM and prediabetes. RESULTS: After adjusting for covariates, positive associations of atrazine, ametryn, and oxadiazon with the increased odds of T2DM were obtained. As for prediabetes, each 1-fold increase in ln-transformed oxadiazon was related to 8.4% (95% confidence interval (CI): 1.033, 1.138) higher odds of prediabetes. In addition, several herbicides were significantly related to fasting plasma glucose, fasting insulin, and HOMA2-IR (false discovery rates adjusted P value < 0.05). Furthermore, the quantile g-computation analysis showed that one quartile increase in multiple herbicides was associated with T2DM (OR (odds ratio): 1.099, 95%CI: 1.043, 1.158), and oxadiazon was assigned the largest positive weight, followed by atrazine. In addition, the ERS calculated by the selected herbicides from AENET were found to be associated with T2DM and prediabetes, and the corresponding ORs and 95%CIs were 1.133 (1.108, 1.159) and 1.065 (1.016, 1.116), respectively. The BKMR analysis indicated a positive association between mixtures of herbicides exposure and the risk of T2DM. CONCLUSIONS: Exposure to mixtures of herbicides was associated with an increased risk of T2DM among Chinese rural population, indicating that the impact of herbicides exposure on diabetes should be paid attention to and measures should be taken to avoid herbicides mixtures exposure.

Cinnamaldehyde induces apoptosis and enhances anti-colorectal cancer activity via covalent binding to HSPD1.

Colorectal cancer (CRC) is a common malignant tumor with high morbidity and mortality rates worldwide. Although surgical resection and adjuvant radiotherapy/chemotherapy are the mainstays of CRC treatment, the efficacy is unsatisfactory due to several limitations, including high drug resistance. Accordingly, there is a dire need for new drugs or a novel combination approach to treat this patient population. Herein, we found that cinnamaldehyde (CA) could exert an antitumor effect in HCT-116 cell lines. Target fishing, molecular imaging, and live-cell tracing using an alkynyl-CA probe revealed that the heat shock 60 kDa protein 1 (HSPD1) protein was the target of CA. The covalent binding of CA with HSPD1 altered its stability. Furthermore, our results demonstrated that CA could induce cell apoptosis by inhibiting the PI3K/Akt signaling pathway and enhanced anti-CRC activity both in vitro and in vivo. Meanwhile, CA combined with different chemotherapeutic agents was beneficial to patients resistant to anti-CRC drug therapy.

Performance of wetland applied to ecological remediation of abandoned fish ponds: A case study in Gonghu Bay, Tai lake.

To restore the abandoned fish ponds to "near natural" state, the wetland restoration was carried out in Gonghu Bay lakeside, and its long-term performance of controlling external load was studied for 5 years. The findings showed that water quality and biodiversity had been improved dramatically after the preliminary transformation. The concentrations of permanganate index (CODMn), total nitrogen (TN), and total phosphorus (TP) obviously decreased from 12.91 mg L-1 to 4.32 mg L-1, from 3.46 mg L-1 to 1.42 mg L-1, and from 0.27 mg L-1 to 0.04 mg L-1, respectively. The proportion of Cyanophyta was effectively reduced from 31.82% to 18.89%, and favored the growth of diatoms (31.82%-37.78%) to be the dominant algae species. Aquatic plant species and coverage gradually increased from 16 to 56 and from 5% to 60%, respectively. An in-deep monitoring done for 5 years (2013-2017) showed that the wetland achieved a satisfactory removal efficiency of 58.95% for TN, 64.60% for TP, and up to 77.83% for chlorophyll-a. Besides, three pollution scenarios, such as stormwater runoff, algal bloom, and continuous water transfer, were selected to explore the tolerance of the wetland to the suddenly increased pollution loads. The results dedicated that even if the inlet load was up to 1.0 × 105 m3 d-1, the removal rate coefficients of wetland for chlorophyll-a, TP, and TN were 0.135-0.239 d-1, 0.041-0.112 d-1, and 0.030-0.109 d-1, respectively, which were equivalent to the well-running wetlands. This study confirmed that the wetland was not only a promising ecological remediation technique to contaminated abandoned fish ponds, but also could withstand high pollution load, which had the prospect of sustainable utilization.

Phenols from Potentilla anserina L. Improve Insulin Sensitivity and Inhibit Differentiation in 3T3-L1 Adipocytes in Vitro.

Potentilla anserina L., a well-known perennial herb, is widely used in traditional Tibetan medicine and used as a delicious food in humans. The present investigation reports on the activity of P. anserina phenols (PAP) in regulating glycolipid metabolism in 3T3-L1 adipocytes. Insulin sensitivity tests showed that PAP improved insulin-stimulated glucose uptake by promoting the phosphorylation of serine/threonine kinase Akt. Moreover, an assay involving the differentiation of 3T3-L1 preadipocytes demonstrated that PAP also decreased the accumulation of lipid droplets by suppressing the expression of adipokines during the differentiation process. In addition, the underlying mechanism from the aspects of energy metabolism and oxidative stress is also discussed. The improvement in energy metabolism was supported by an increase in mitochondrial membrane potential (MMP) and intracellular ATP. Amelioration of oxidative stress was supported by decreased levels of intracellular reactive oxygen species (ROS). In summary, our findings suggest that PAP can ameliorate the disorder of glycolipid metabolism in insulin resistant 3T3-L1 adipocytes by improving energy metabolism and oxidative stress and might be an attractive candidate for the treatment of diabetes.

Functional disparity of four pheromone-binding proteins from the plum fruit moth Grapholita funebrana Treitscheke in detection of sex pheromone components.

Grapholita funebrana, also known as the plum fruit moth, is an oligophagous pest species that causes enormous economic losses of the fruits of Rosaceae. An eco-friendly method for the control of G. funebrana besides chemical control has not yet been developed. The sex pheromone communication system plays an important role in moth courtship and mating, in which pheromone-binding proteins (PBPs) are critical. In this research, we identified four PBPs, namely, GfunPBP1.1, GfunPBP1.2, GfunPBP2, and GfunPBP3, from the antennae of G. funebrana. The results of real-time quantitative PCR (RT-qPCR) showed that all four GfunPBPs were overwhelmingly expressed in the antennae and that GfunPBP1.2 and GfunPBP2 showed male-biased expression patterns, whereas GfunPBP1.1 and GfunPBP3 were equally expressed between sexes. The results of ligand-binding assays illustrated that although all four recombinant GfunPBPs (rGfunPBPs) had binding activity with the tested sex pheromone compounds, their preferred ligands were significantly different. rGfunPBP2 had the strongest binding affinity to Z8-12:Ac and Z8-12:OH; rGfunPBP1.1 preferred to bind Z8-14:Ac, Z10-14:Ac, and 12:OH more than to the other three GfunPBPs; and rGfunPBP1.2 exhibited stronger binding affinity to E8-12:Ac than to the other rGfunPBPs. Molecular docking results demonstrated that hydrophobic forces, especially van der Waals forces and hydrogen bonds, were the most important forces that maintained GfunPBP-pheromone ligand complexes. This study will improve our understanding of the sex pheromone recognition mechanisms of G. funebrana and promote the development of novel strategies for controlling G. funebrana.

New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177).

Prostate-specific membrane antigen (PSMA) is a promising target for the diagnosis and radionuclide therapy of prostate cancer. This study reports conversion of a previously reported 68Ga-imaging agent, [68Ga]Ga-P16-093, to a Lu-177 radionuclide therapeutic agent. Substitution of the HBED-CC metal chelating group with DOTA(GA)2 led to P17-087 (4) and P17-088 (7). Both agents showed excellent PSMA binding affinity (IC50 = 10-30 nM) comparable to that of recently FDA-approved [177Lu]Lu-PSMA-617 (Pluvicto). Biodistribution studies in PSMA expressing tumor bearing mice showed that [177Lu]Lu-4 exhibited very high tumor uptake and a fast blood clearance similar to those of [177Lu]Lu-PSMA-617. Conversely, [177Lu]Lu-7, containing an albumin binder, extended its blood half-life and exhibited significantly higher uptake and longer tumor residence time than [177Lu]Lu-4 and [177Lu]Lu-PSMA-617. The switch from chelator HBED-CC to DOTA(GA)2 and the switch from the imaging isotope gallium-68 to the therapeutic isotope lutetium-177 have successfully transformed a PSMA-targeting agent from diagnosis to promising radionuclide therapeutic agents.

Cookies Fortified with Lonicera japonica Thunb. Extracts: Impact on Phenolic Acid Content, Antioxidant Activity and Physical Properties.

Lonicera japonica Thunb [...].

Influence of traditional Chinese medicines on the in vivo metabolism of lopinavir/ritonavir based on UHPLC-MS/MS analysis.

A fast, reliable, and cost-effective liquid chromatography-tandem mass spectrometry method was established to determine the effects of the traditional Chinese medicine employed to treat coronavirus disease 2019, namely, Lianhua Qingwen granules, Huoxiang Zhengqi capsules, Jinhua Qinggan granules, Shufeng Jiedu capsules, and Angong Niuhuang pills, on the pharmacokinetics of lopinavir/ritonavir in rats. Blood samples were prepared using the protein precipitation method and atazanavir was selected as the internal standard (IS). Separation was performed on an Agilent ZORBAX eclipse plus C18 (2.1 mm × 50 mm, 1.8 µm) column using acetonitrile and water containing 0.1% formic acid as the mobile phase for gradient elution. The flow rate was 0.4 mL/min and the injection volume was 2 µL. Agilent Jet Stream electrospray ionization was used for mass spectrometry detection under positive ion multiple reaction monitoring mode at a transition of m/z 629.3→447.3 for lopinavir, m/z 721.3→296.1 for ritonavir, and m/z 705.4→168.1 for the IS. The method showed good linearity in the concentration range of 25-2500 ng/mL (r=0.9981) for lopinavir and 5-500 ng/mL (r=0.9984) for ritonavir. The intra-day and inter-day precision and accuracy were both within ±15%. Items, such as dilution reliability and residual effect, were also within the acceptable limits. The method was used to determine the effects of five types of traditional Chinese medicines on the pharmacokinetics of lopinavir/ritonavir in rats. The pharmacokinetic results showed that the half-life of ritonavir in the groups administered Lianhua Qingwen granules and Huoxiang Zhengqi capsules combined with lopinavir/ritonavir was prolonged by approximately 1.5- to 2-fold relative to that in the control group. Similarly, the pharmacokinetic parameters of lopinavir were altered. Overall, the results of this study offer important theoretical parameters for the effective clinical use of five types of traditional Chinese medicines combined with lopinavir/ritonavir to reduce the occurrence of clinical adverse reactions.

Cell-Traction-Triggered On-Demand Electrical Stimulation for Neuron-Like Differentiation.

Electromechanical interaction of cells and extracellular matrix are ubiquitous in biological systems. Understanding the fundamentals of this interaction and feedback is critical to design next-generation electroactive tissue engineering scaffold. Herein, based on elaborately modulating the dynamic mechanical forces in cell microenvironment, the design of a smart piezoelectric scaffold with suitable stiffness analogous to that of collagen for on-demand electrical stimulation is reported. Specifically, it generated a piezoelectric potential, namely a piezopotential, to stimulate stem cell differentiation with cell traction as a loop feedback signal, thereby avoiding the unfavorable effect of early electrical stimulation on cell spreading and adhesion. This is the first time to adapt to the dynamic microenvironment of cells and meet the electrical stimulation of cells in different states by a constant scaffold, diminishing the cumbersomeness of inducing material transformation or trigging by an external stimulus. This in situ on-demand electrical stimulation based on cell-traction-mediated piezopotential paves the way for smart scaffolds design and future bioelectronic therapies.

Luteolin combined with low-dose paclitaxel synergistically inhibits epithelial-mesenchymal transition and induces cell apoptosis on esophageal carcinoma in vitro and in vivo.

Although paclitaxel is a promising frontline chemotherapy agent for various malignancies, the clinical applications have been restricted by side effects, drug resistance, and cancer metastasis. The combination of paclitaxel and other agents could be the promising strategies against malignant tumor, which enhances the antitumor effect through synergistic effects, reduces required drug concentrations, and also suppresses tumorigenesis in multiple ways. In this study, we found that luteolin, a natural flavonoid compound, combined with low-dose paclitaxel synergistically regulated the proliferation, migration, epithelial-mesenchymal transition (EMT), and apoptosis of esophageal cancer cells in vitro, as well as synergistically inhibited tumor growth without obvious toxicity in vivo. The molecular mechanism of inhibiting cell migration and EMT processes may be related to the inhibition of SIRT1, and the mechanism of apoptosis induction is associated with the reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK) pathway-mediated activation of mitochondrial apoptotic pathway.

Electroactive Biomaterials and Systems for Cell Fate Determination and Tissue Regeneration: Design and Applications.

During natural tissue regeneration, tissue microenvironment and stem cell niche including cell-cell interaction, soluble factors, and extracellular matrix (ECM) provide a train of biochemical and biophysical cues for modulation of cell behaviors and tissue functions. Design of functional biomaterials to mimic the tissue/cell microenvironment have great potentials for tissue regeneration applications. Recently, electroactive biomaterials have drawn increasing attentions not only as scaffolds for cell adhesion and structural support, but also as modulators to regulate cell/tissue behaviors and function, especially for electrically excitable cells and tissues. More importantly, electrostimulation can further modulate a myriad of biological processes, from cell cycle, migration, proliferation and differentiation to neural conduction, muscle contraction, embryogenesis, and tissue regeneration. In this review, endogenous bioelectricity and piezoelectricity are introduced. Then, design rationale of electroactive biomaterials is discussed for imitating dynamic cell microenvironment, as well as their mediated electrostimulation and the applying pathways. Recent advances in electroactive biomaterials are systematically overviewed for modulation of stem cell fate and tissue regeneration, mainly including nerve regeneration, bone tissue engineering, and cardiac tissue engineering. Finally, the significance for simulating the native tissue microenvironment is emphasized and the open challenges and future perspectives of electroactive biomaterials are concluded.

Novel pH-Triggered Doxorubicin-Releasing Nanoparticles Self-Assembled by Functionalized ß-Cyclodextrin and Amphiphilic Phthalocyanine for Anticancer Therapy.

Cyclodextrins (CDs), as pharmaceutical excipients with excellent biocompatibility, non-immunogenicity, and low toxicity in vivo, are widely used to carry drugs by forming inclusion complexes for improving the solubility and stability of drugs. However, the limited space of CDs' lipophilic central cavity affects the loading of many drugs, especially with larger molecules. In this study, ß-CDs were modified by acetonization to improve the affinity for the chemotherapy drug doxorubicin (DOX), and doxorubicin-adsorbing acetalated ß-CDs (Ac-CD:DOX) self-assembled to nanoparticles, followed by coating with the amphiphilic zinc phthalocyanine photosensitizer ZnPc-(PEG)5 for antitumor therapy. The final product ZnPc-(PEG)5:Ac-CD:DOX was demonstrated to have excellent stability and pH-sensitive drug release characteristics. The cell viability and apoptosis assay showed synergistic cytotoxic effects of chemotherapy and phototherapy. The mechanism of cytotoxicity was analyzed in terms of intracellular reactive oxygen species, mitochondrial membrane potential, and subcellular localization. More importantly, in vivo experiments indicated that ZnPc-(PEG)5:Ac-CD:DOX possessed significant tumor targeting, prominent antitumor activity, and less side effects. Our strategy expands the application of CDs as drug carriers and provides new insights into the development of CD chemistry.

Grape seed proanthocyanidins protect retinal ganglion cells by inhibiting oxidative stress and mitochondrial alteration.

Grape seed proanthocyanidins (GSP) are known as condensed tannins and have been used as an anti-oxidant in various neurodegenerative diseases. In our study, GSP was used as a daily dietary supplement and the neuroprotective effects were evaluated on the retinal ganglion cells (RGCs) in the retinal tissues in glaucomatous DBA/2D (D2) mice. D2 mice and age-matched non-glaucomatous DBA/2J-Gpnmb+ (D2-Gpnmb+) mice were fed with GSP or a control diet for up to 6 months. The intraocular pressure (IOP), RGC survival, glial fibrillary acidic protein (GFAP), the levels of apoptotic proteins, and the expression of oxidative stress markers in retinal tissues were determined. In our study, the neuroprotective effects of GSP on retinal tissues were confirmed, as evidenced by (a) GSP inhibited the IOP elevation in D2 mice; (b) GSP enhanced RGC survival and mediated the apoptotic protein expression; (c) GSP suppressed GFAP expression; and (d) the oxidative stress and the levels of mitochondrial reactive oxygen species were regulated by GSP. Our findings indicate that GSP has promising potential to preserve retinal tissue functions via regulating oxidative stress and mitochondrial functions.

Non-active antibiotic and bacteriophage synergism to successfully treat recurrent urinary tract infection caused by extensively drug-resistant Klebsiella pneumoniae.

We report a case of a 63-year-old female patient who developed a recurrent urinary tract infection (UTI) with extensively drug-resistant Klebsiella pneumoniae (ERKp). In the initial two rounds of phage therapy, phage resistant mutants developed within days. Although ERKp strains were completely resistant to sulfamethoxazole-trimethoprim, the combination of sulfamethoxazole-trimethoprim with the phage cocktail inhibited the emergence of phage resistant mutant in vitro, and the UTI of patient was successfully cured by this combination. Thus, we propose that non-active antibiotic and bacteriophage synergism (NABS) might be an alternative strategy in personalized phage therapy.

Brain activity regulates loose coupling between mitochondrial and cytosolic Ca2+ transients.

Mitochondrial calcium ([Ca2+]mito) dynamics plays vital roles in regulating fundamental cellular and organellar functions including bioenergetics. However, neuronal [Ca2+]mito dynamics in vivo and its regulation by brain activity are largely unknown. By performing two-photon Ca2+ imaging in the primary motor (M1) and visual cortexes (V1) of awake behaving mice, we find that discrete [Ca2+]mito transients occur synchronously over somatic and dendritic mitochondrial network, and couple with cytosolic calcium ([Ca2+]cyto) transients in a probabilistic, rather than deterministic manner. The amplitude, duration, and frequency of [Ca2+]cyto transients constitute important determinants of the coupling, and the coupling fidelity is greatly increased during treadmill running (in M1 neurons) and visual stimulation (in V1 neurons). Moreover, Ca2+/calmodulin kinase II is mechanistically involved in modulating the dynamic coupling process. Thus, activity-dependent dynamic [Ca2+]mito-to-[Ca2+]cyto coupling affords an important mechanism whereby [Ca2+]mito decodes brain activity for the regulation of mitochondrial bioenergetics to meet fluctuating neuronal energy demands as well as for neuronal information processing.

Efficacy analysis of a novel thermochemotherapy scheme with pirarubicin for intermediate- and high-risk nonmuscle-invasive bladder cancer: a single-institution nonrandomized concurrent controlled trial.

Objective: To compare the efficacy and safety of a novel thermochemotherapy scheme and the instillation of pirarubicin (THP) without hyperthermia in patients with intermediate- and high-risk nonmuscle-invasive bladder cancer (NMIBC). Materials and methods: Between June 2012 and December 2016, 300 patients with urothelial carcinoma of the bladder undergoing intravesical adjuvant therapy with THP after transurethral resection of bladder tumors (TURBT) were enrolled in the study. These patients were divided into the CTHC group (thermochemotherapy composed of three consecutive sessions in which only the second hyperthermia was combined with THP, followed by intravesical instillation with THP without using hyperthermia) and the THP group (instillation of THP without hyperthermia). Cystoscopy and urinary cytology were repeated every 3 months. The primary endpoint was 24-month recurrence-free survival (RFS). Secondary endpoints included 24-month progression-free survival (PFS) and adverse event (AE) rates. Results: Baseline characteristics of the CTHC (n = 76) and THP (n = 85) groups were well-balanced. The 24-month RFS was 82.9% in the CTHC group and 63.5% in the THP group (log-rank p = .008). A significantly higher percentage of patients in the CTHC group achieved PFS than in the THP group (97.4% versus 87.1%; log-rank p = .011). There was no significant difference in AEs between the two groups (p > .05). Based on Cox proportional hazards models, CTHC was the only factor that contributed independently to improved RFS (hazard ratio, 0.422; 95% confidence interval, 0.214-0.835; p = .013). Conclusion: The CTHC scheme is a safe and effective adjuvant treatment option after TURBT for patients with intermediate- and high-risk NMIBC.