Components Analysis of San-Bai Decoction, and Its Pharmacodynamics and Mechanism on Preventing and Treating Melasma.

ETHNOPHARMACOLOGICAL RELEVANCE: San-Bai Decoction (SBD) is a classic whitening prescription originally recorded in the 'Introduction to Medicine' of the Ming Dynasty. SBD has been known for invigorating Qi and blood, promoting spleen and stomach, whitening skin, and fading melasma. However, its pharmacodynamic material basis and specific mechanism remain unclear. AIM OF THE STUDY: The aim of this study is to clarify the pharmacodynamic material basis of SBD and its mechanism of removing melasma. MATERIALS AND METHODS: The positive and negative ion mass spectrum data of SBD extract were collected by UHPLC-Q-Exactive Orbitrap MS/MS, imported into Compound Discoverer (CD) 3.1 software, matched through the online database, and manually checked. Finally, the in vitro chemical components of SBD were classified. Similarly, the mass spectrum data of SBD in the serum of normal rats and melasma model rats were also analyzed by CD 3.1 software. The in vitro identified Compound file of SBD was imported into the Expected Compounds and the Generate Expected Compounds project was selected. The SBD compounds were then chosen under the Compound Section. All phase I and II reaction types related to SBD components were selected, and the metabolic platform of CD 3.1 software was utilized to process the results and obtain possible metabolites. The metabolites were scored and products with high scores were subsequently screened. According to literature comparison, the final metabolites of SBD in both normal rats and melasma model rats were determined and comprehensively analyzed. The Melasma model rats were constructed through intramuscular injection of progesterone and ultraviolet radiation B (UVB) irradiation. The preventing and treating effect of SBD on melasma were evaluated by regulating inflammation, epidermal collagen content, and oxidative stress. Additionally, the effect of SBD on the Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (Akt)/Glycogen synthase kinase 3ß (GSK3ß) pathway was investigated through Western blot (WB) to explore its underlying mechanism on whitening and removing melasma efficacy. RESULTS: Ultimately, 94 components were identified in SBD, including 41 flavonoids, 27 organic acids, and 9 glycosides, 3 terpenoids, 2 amides, 2 aldehydes, 1 phenylpropanoid and 9 other compounds. In the blood of normal rat group, a total of 24 prototype components and 61 metabolites were identified. Similarly, there were19 prototype components and 44 metabolites identified from the blood of melasma model rats. Pharmacodynamic experiment results indicated that SBD effectively reduced the incidence of melasma, prevent the loss of epidermal collagen, and elevate the activity of superoxide dismutase and decrease the malondialdehyde content in both liver and skin. Interestingly, the WB results demonstrated that SBD effectively activated PI3K/Akt/GSK3ß pathway, and down-regulated the expression of melanin-related proteins. CONCLUSIONS: For the first time, the components of SBD extracts, and its prototype components and metabolites in the blood of normal rats and melasma model rats were successfully identified by high-resolution liquid chromatography-mass spectrometry with CD software. Additionally, the differences of in vivo components of SBD between normal rats and melasma model rats were analyzed. The preventive and therapeutic effect of SBD on melasma was verified in the melasma model rats induced by progesterone and UVB irradiation, and its mechanism was related to activating PI3K/Akt/GSK3ß pathway and downregulating the expression of melanin-related proteins. These results provide an experimental foundation for further research on the pharmacodynamic substance basis and pharmacodynamic mechanism of SBD, as well as developing new anti-melasma formula with SBD.

W-GA nanodots restore intestinal barrier functions by regulating flora disturbance and relieving excessive oxidative stress to alleviate colitis.

Inflammatory bowel disease (IBD) may arise due to disruption of mucosal barriers as a result of dysregulation of the intestinal flora and excessive oxidative stress. The creation of nanomaterials with only microbiota-regulating effects often leads to inadequate therapeutic outcomes caused by the disruption of a healthy microbial balance and the emergence of tissue harm caused by excessive oxidative stress. This report describes the multifunctional activity of ultrasmall W-GA nanodots, which can precisely regulate the intestinal microbiome by inhibiting the abnormal expansion of Enterobacteriaceae during colitis and alleviating the damage caused by oxidative stress to the reconstructive microflora, ultimately restoring intestinal barrier function. W-GA nanodots have been synthesized through a simple coordination reaction and can be dispersed in various solvents in vitro, demonstrating favorable safety profiles in cells, significant clearance of reactive oxygen and nitrogen species (RONS), and increased cell survival in models of oxidative stress induced by hydrogen peroxide (H2O2). Through oral or intravenous administration, the W-GA nanodots were shown to be highly safe when tested in vivo, and they effectively reduced colon damage in mice with DSS-induced colitis by restoring the integrity of the intestinal barrier. W-GA nanodots have enabled the integration of microflora reprogramming and RONS clearance, creating a potent therapeutic strategy for treating gut inflammation. Consequently, the development of W-GA nanodots represents a promising strategy for enhancing the formation and preservation of the intestinal barrier to treat IBDs by suppressing the growth of Enterobacteriaceae, a type of facultative anaerobic bacterium, and facilitating the effective removal of RONS. Ultimately, this leads to the restoration of the intestinal barrier's functionality. STATEMENT OF SIGNIFICANCE: An increasing number of nanoparticles are under development for treating inflammatory bowel disease. Although they can alleviate inflammation symptoms by regulating reactive oxygen and nitrogen species (RONS) and microbiota, their understanding of the mechanism behind microbiota regulation is limited. This study synthesized W-GA nanodots using a straightforward one-pot synthesis method. Simple synthesis holds significant promise for clinical applications, as it encompasses multiple nanoenzyme functions and also exhibits Enterobacteriaceae inhibitory properties.Thus, it contributes to ameliorating the current medical landscape of inflammatory bowel disease.

Recent progress on engineered micro/nanomaterials mediated modulation of gut microbiota for treating inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a type of chronic recurrent inflammation disease that mainly includes Crohn's disease and ulcerative colitis. Currently, the treatments for IBD remain highly challenging, with clinical treatment drugs showing limited efficacy and adverse side effects. Thus, developing drug candidates with comprehensive therapeutic effects, high efficiency, and low toxicity is urgently needed. Recently, micro/nanomaterials have attracted considerable interest because of their bioavailability, multitarget and efficient effects on IBD. In addition, gut modulation plays a substantial role in restoring intestinal homeostasis. Therefore, efficient microbiota-based strategies modulating gut microenvironment have great potential in remarkably treating IBD. With the development of micro- and nanomaterials for the treatment of IBD and more in-depth studies of their therapeutic mechanisms, it has been found that these treatments also have a tendency to positively regulate the intestinal flora, resulting in an increase in the beneficial flora and a decrease in the level of pathogenic bacteria, thus regulating the composition of the intestinal flora to a normal state. In this review, we first present the interactions among the immune system, intestinal barrier, and gut microbiome. In addition, recent advances in administration routes and methods that positively arouse the regulation of intestinal flora for IBD using probiotics, prebiotics, and redox-active micro/nanomaterials have been reviewed. Finally, the key challenges and critical perspectives of gut microbiota-based micro/nanomaterial treatment are also discussed.

Endoscopic Submucosal Dissection Criteria for Differentiated-type Early Gastric Cancer Are Applicable to Mixed-type Differentiated Predominant.

BACKGROUND: There is a lack of sufficient evidence on whether mixed-type differentiated predominant early gastric cancer (MD-EGC) can be treated endoscopically by referring to the criteria for differentiated-type early gastric cancer (EGC). This study aims to evaluate the efficacy of endoscopic submucosal dissection (ESD) in MD-EGC. METHODS: Patients with differentiated-type EGC treated with ESD first from January 2015 to June 2021 were reviewed, including MD-EGC and pure differentiated-type EGC (PD-EGC). Clinical data, including the clinicopathological characteristics, resection outcomes of ESD, and recurrence and survival time, were collected, and the difference between MD-EGC and PD-EGC was tested. RESULTS: A total of 48 patients (48 lesions) with MD-EGC and 850 patients (890 lesions) with PD-EGC were included. Compared with PD-EGC, MD-EGC had a higher submucosal invasion rate (37.5% vs. 13.7%, P<0.001) and lymphatic invasion rate (10.4% vs. 0.4%, P<0.001). The rates of complete resection (70.8% vs. 92.5%, P<0.001) and curative resection (54.2% vs. 87.4%, P<0.001) in MD-EGC were lower than those of PD-EGC. Multivariate analysis revealed that MD-EGC (OR 4.26, 95% CI, 2.22-8.17, P<0.001) was an independent risk factor for noncurative resection. However, when curative resection was achieved, there was no significant difference in the rates of recurrence (P=0.424) between the 2 groups, whether local or metachronous recurrence. Similarly, the rates of survival(P=0.168) were no significant difference. CONCLUSIONS: Despite the greater malignancy and lower endoscopic curative resection rate of MD-EGC, patients who met curative resection had a favorable long-term prognosis.

Long-term efficacy of peroral endoscopic myotomy for achalasia under different criteria.

BACKGROUND: Peroral endoscopic myotomy (POEM) has emerged as a widely accepted treatment for achalasia, with limited studies for over 2 years. Additionally, traditional measurements of achalasia after POEM have deficiencies. The study aimed to analyze the long-term outcomes of POEM under different criteria. METHODS: Patients with achalasia who received POEM between November 2012 and March 2021 were recruited. Patients and characteristics were shown, and risk factors related to two novel definitions of recurrence, symptomatic reflux, and reflux esophagitis were analyzed. RESULTS: Three hundred and twenty-one patients were included. At a median follow-up of 52 months, twenty-three failures happened (7.17%) under the modified criterion, and forty-seven failures occurred (14.64%) under the normal standard. Hospitalization (P = 0.027) and esophageal myotomy length (P = 0.039) were significantly associated with long-term efficacy under the modified and normal criteria, respectively. Fifty-two patients (16.20%) reported reflux symptoms and endoscopy performed in 88 patients revealed reflux esophagitis in 22 cases (25.00%). There were no predictors in the analysis of symptomatic reflux and gender (P = 0.010), LESP (P = 0.013), IRP (P = 0.015), and the esophageal myotomy length (P = 0.032) were statistically related to reflux esophagitis. CONCLUSION: POEM is an extremely safe and effective treatment for achalasia with long-term follow-up. Shorter hospitalization and shorter esophageal myotomy length may decrease the incidence of recurrence under the modified and normal criteria, respectively. Long-term outcomes of POEM are unpredictable. No risk factors were related to symptomatic reflux, and male patients with low preoperative LESP and IRP needed relatively shorter esophageal myotomy to prevent reflux esophagitis.

Rapid Cryptococcus electroporated-lysis and sensitive detection on a miniaturized platform.

Fast and accurate detection of Cryptococcus and precise differentiation of its subtypes is of great significance in protecting people from cryptococcal disease and preventing its spread in populations. However, traditional Cryptococcus identification and detection techniques still face significant challenges in achieving high analysis speed as well as high sensitivity. In this work, we report an electric microfluidic biochip. Compared to conventional methods that take several hours or even a day, this chip can detect Cryptococcus within 20 min, and achieve its maximum detection limit within 1 h, with the ability to differentiate between the Cryptococcus neoformans (NEO) and rare Cryptococcus gattii (GAT) efficiently, which accounts for nearly 100%. This device integrated two functional zones of an electroporation lysis (EL) zone for rapid cell lysis (<30 s) and an electrochemical detection (ED) zone for sensitive analysis of the released nucleic acids. The EL zone adopted a design of microelectrode arrays, which obtains a large electric field intensity at the constriction of the microchannel, addressing the safety concerns associated with high-voltage lysis. The device enables a limit of detection (LOD) of 60 pg/mL for NEO and 100 pg/mL for GAT through the modification of nanocomposites and specific probes. In terms of the detection time and sensitivity, the integrated microfluidic biochip demonstrates broad potential in Cryptococcus diagnosis and disease prevention.

The progression of inorganic nanoparticles and natural products for inflammatory bowel disease.

There is a growing body of evidence indicating a close association between inflammatory bowel disease (IBD) and disrupted intestinal homeostasis. Excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with an increase in M1 proinflammatory macrophage infiltration during the activation of intestinal inflammation, plays a pivotal role in disrupting intestinal homeostasis in IBD. The overabundance of ROS/RNS can cause intestinal tissue damage and the disruption of crucial gut proteins, which ultimately compromises the integrity of the intestinal barrier. The proliferation of M1 macrophages contributes to an exaggerated immune response, further compromising the intestinal immune barrier. Currently, intestinal nanomaterials have gained widespread attention in the context of IBD due to their notable characteristics, including the ability to specifically target regions of interest, clear excess ROS/RNS, and mimic biological enzymes. In this review, we initially elucidated the gut microenvironment in IBD. Subsequently, we delineate therapeutic strategies involving two distinct types of nanomedicine, namely inorganic nanoparticles and natural product nanomaterials. Finally, we present a comprehensive overview of the promising prospects associated with the application of nanomedicine in future clinical settings for the treatment of IBD (graphic abstract). Different classes of nanomedicine are used to treat IBD. This review primarily elucidates the current etiology of inflammatory bowel disease and explores two prominent nanomaterial-based therapeutic approaches. First, it aims to eliminate excessive reactive oxygen species and reactive nitrogen species. Second, they focus on modulating the polarization of inflammatory macrophages and reducing the proportion of pro-inflammatory macrophages. Additionally, this article delves into the treatment of inflammatory bowel disease using inorganic metal nanomaterials and natural product nanomaterials.

Urchin-like Fe3O4@Bi2S3 Nanospheres Enable the Destruction of Biofilm and Efficiently Antibacterial Activities.

Biofilm-associated infections (BAIs) have been considered a major threat to public health, which induce persistent infections and serious complications. The poor penetration of antibacterial agents in biofilm significantly limits the efficiency of combating BAIs. Magnetic urchin-like core-shell nanospheres of Fe3O4@Bi2S3 were developed for physically destructing biofilm and inducing bacterial eradication via reactive oxygen species (ROS) generation and innate immunity regulation. The urchin-like magnetic nanospheres with sharp edges of Fe3O4@Bi2S3 exhibited propeller-like rotation to physically destroy biofilm under a rotating magnetic field (RMF). The mild magnetic hyperthermia improved the generation of ROS and enhanced bacterial eradication. Significantly, the urchin-like nanostructure and generated ROS could stimulate macrophage polarization toward the M1 phenotype, which could eradicate the persistent bacteria with a metabolic inactivity state through phagocytosis, thereby promoting the recovery of implant infection and inhibiting recurrence. Thus, the design of magnetic-driven sharp-shaped nanostructures of Fe3O4@Bi2S3 provided enormous potential in combating biofilm infections.

APTES-mediated Cu2(OH)3(NO3) nanomaterials on the surface of silicone catheters for abscess.

Metal-based nanomaterials have remarkable bactericidal effects; however, their toxicity cannot be disregarded. To address this concern, we developed a simple synthesis route for antibacterial catheters using metal-based nanomaterials to reduce toxicity while harnessing their excellent bactericidal properties. The grafting agent (3-aminopropyl)triethoxysilane (APTES) forms -NH2 groups on the catheter surface, onto which copper ions form a nanomaterial complex known as Cu2(OH)3(NO3) (defined as SA-Cu). The synthesized SA-Cu exhibited outstanding contact antibacterial effects, as observed through scanning electron microscopy (SEM), which revealed cell membrane crumbing and bacterial rupture on the catheter surface. Furthermore, SA-Cu exhibited excellent biosafety characteristics, as evidenced by the cell counting kit-8 (CCK-8) assay, which showed no significant cytotoxicity. SA-Cu demonstrated sustained antimicrobial capacity, with in vivo experiments demonstrating over 99% bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) for two weeks. The transcriptome sequencing results suggested that SA-Cu may exert its bactericidal effects by interfering with histidine and purine metabolism in MRSA. This study presents a straightforward method for synthesizing antimicrobial silicone catheters containing copper nanomaterials using copper ions.

2D Nanozymes Modulate Gut Microbiota and T-Cell Differentiation for Inflammatory Bowel Disease Management.

Intestinal commensal microbiota dysbiosis and immune dysfunction are significant exacerbating factors in inflammatory bowel disease (IBD). To address these problems, Pluronic F-127-coated tungsten diselenide (WSe2 @F127) nanozymes are developed by simple liquid-phase exfoliation. The abundant valence transitions of elemental selenium (Se2- /Se4+ ) and tungsten (W4+ /W6+ ) enable the obtained WSe2 @F127 nanozymes to eliminate reactive oxygen/nitrogen species. In addition, the released tungsten ions are capable of inhibiting the proliferation of Escherichia coli. In a model of dextran sodium sulfate-induced colitis, WSe2 @F127 nanozymes modulate the gut microbiota by increasing the abundance of bacteria S24-7 and significantly reducing the abundance of Enterobacteriaceae. Moreover, WSe2 @F127 nanozymes inhibit T-cell differentiation and improve intestinal immune barrier function in a model of Crohn's disease. The WSe2 @F127 nanozymes effectively alleviate IBD by reducing oxidative stress damage, modulating intestinal microbial populations, and remodeling the immune barrier.

Au Nanorods Activated the Zn/Ce Composites with Cancer Cell Specific Cytotoxicity for Enhanced Chemodynamic Therapy.

Chemodynamic therapy based on the Fenton reaction has been developed as an extremely promising modality for cancer therapeutics. In this study, a core-shell structure nanoplatform was constructed by a Au nanorod externally encapsulating Ce/Zn-based composites (ACZO). The nanoparticles can catalyze the generation of reactive oxygen species (ROS) under acidic conditions and effectively consume existing glutathione (GSH) to destroy the redox balance within the tumor. Moreover, the decomposition of the nanocomplexes under acidic conditions releases large amounts of zinc ions, leading to zinc overload in cancer cells. The photothermal effect generated by the Au nanorods not only provides photothermal therapy (PTT) but also augments the catalytic reaction and ions action mentioned above. This facile strategy to improve the efficacy of chemodynamic therapy by the photothermal enhancement of catalytic activity and zinc ion release provides a promising perspective for potential tumor treatment.

Engineering Hyaluronic Acid Microneedles Loaded with Mn2+ and Temozolomide for Topical Precision Therapy of Melanoma.

Topical therapy has received worldwide attention for in situ tumors owing to its higher efficacy of drug delivery. Herein, this work reports a dissolvable multifunctional hyaluronic acid microneedles (HMNs) patch coloaded with temozolomide (TMZ) and MnCl2 (TMZ/MnCl2@HMN) for chemoimmunotherapy of melanoma. HMNs can ensure the stability of TMZ over time, and exhibit fewer side effects with a localized release way. In particular, TMZ not only promotes dendritic cell maturation by triggering immunogenic cell death in tumor cells, but also induces DNA damage that can further enhance the Mn2+-activated cGAS-STING (stimulator of interferon genes pathway). As a result, the TMZ/MnCl2@HMN multifunctional platform significantly inhibits lung metastases for melanoma, providing a practical strategy for precision therapy of melanoma.

Topical bismuth oxide-manganese composite nanospheres alleviate atopic dermatitis-like inflammation.

Atopic dermatitis (AD) is a common skin disease involving important immune mechanisms. There is an unmet need for a treatment for this condition. Herein, we focused on elucidating the role of Bi2-xMnxO3 nanospheres (BM) in alleviating skin inflammation in AD-like C57BL/6 mice. The BM was fabricated via sacrificial templates and its biosafety was systematically evaluated. The BM was applied topically to skin lesions of AD-like C57BL/6 mice. The phenotypic and histological changes in the skin were examined carefully. The responses of barrier proteins, inflammatory cytokines and cells to BM were evaluated in HaCaT cells and AD mouse models. The data demonstrated that BM treatment alleviated the AD phenotypes and decreased the level of inflammatory factors, while increasing the expression of the barrier proteins filaggrin/involucrin in the skin. BM effectively reduced the expression of phosphorylated STAT6, which in turn reduced the expression of GATA3, and further decreased the differentiation ratio of Th2 cells, thereby reducing the expression of IL-4. In conclusion, topical drug therapy with BM provides a safe and effective treatment modality for AD by reducing IL-4 and increasing barrier proteins.

Multifunctional Au@AgBiS2 Nanoparticles as High-Efficiency Radiosensitizers to Induce Pyroptosis for Cancer Radioimmunotherapy.

Radiotherapy (RT), a widely used clinical treatment modality for cancer, uses high-energy irradiation for reactive oxygen species (ROS) production and DNA damage. However, its therapeutic effect is primarily limited owing to insufficient DNA damage to tumors and harmful effects on normal tissues. Herein, a core-shell structure of metal-semiconductors (Au@AgBiS2 nanoparticles) that can function as pyroptosis inducers to both kill cancer cells directly and trigger a robust anti-tumor immune against 4T1 triple-negative murine breast cancer and metastasis is rationally designed. Metal-semiconductor composites can enhance the generation of considerable ROS and simultaneously DNA damage for RT sensitization. Moreover, Au@AgBiS2 , a pyroptosis inducer, induces caspase-3 protein activation, gasdermin E cleavage, and the release of damage-associated molecular patterns. In vivo studies in BALB/c mice reveal that Au@AgBiS2 nanoparticles combined with RT exhibit remarkable antitumor immune activity, preventing tumor growth, and lung metastasis. Therefore, this core-shell structure is an alternative for designing highly effective radiosensitizers for radioimmunotherapy.

Recent advances on emerging nanomaterials for diagnosis and treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder that affects the entire gastrointestinal tract and is associated with an increased risk of colorectal cancer. Mainstream clinical testing methods are time-consuming, painful for patients, and insufficiently sensitive to detect early symptoms. Currently, there is no definitive cure for IBD, and frequent doses of medications with potentially severe side effects may affect patient response. In recent years, nanomaterials have demonstrated considerable potential for IBD management due to their diverse structures, composition, and physical and chemical properties. In this review, we provide an overview of the advances in nanomaterial-based diagnosis and treatment of IBD in recent five years. Multi-functional bio-nano platforms, including contrast agents, near-infrared (NIR) fluorescent probes, and bioactive substance detection agents have been developed for IBD diagnosis. Based on a series of pathogenic characteristics of IBD, the therapeutic strategies of antioxidant, anti-inflammatory, and intestinal microbiome regulation of IBD based on nanomaterials are systematically introduced. Finally, the future challenges and prospects in this field are presented to facilitate the development of diagnosis and treatment of IBD.

Hafnium carbide nanoparticles for noninflammatory photothermal cancer therapy.

Photothermal therapy (PTT) effectively suppresses tumor growth with high selectivity. Nevertheless, PTT may cause an inflammatory response that leads to tumor recurrence and treatment resistance, which are the main disadvantages of PTT. Herein, monodisperse hafnium carbide nanoparticles (HfC NPs) were successfully prepared for noninflammatory PTT of cancer. HfC NPs possessed satisfactory near-infrared (NIR) absorption, good photothermal conversion efficiency (PTCE, 36.8 %) and photothermal stability. Furthermore, holding large surface areas and intrinsic redox-active sites, HfC NPs exhibited excellent anti-inflammatory properties due to their antioxidant and superoxide dismutase (SOD) enzymatic activities. In vitro and in vivo experiments confirmed that HfC NPs converted light energy into heat energy upon NIR laser irradiation to kill cancer cells through PTT and achieved a better therapeutic effect by anti-inflammatory effects after PTT. This work highlights that multifunctional HfC NPs can be applied in noninflammatory PTT with outstanding safety and efficacy.

Cancer cell membrane-coated upconversion nanoparticles/ZnxMn1-xS core-shell nanoparticles for targeted photodynamic and chemodynamic therapy of pancreatic cancer.

Oxidative stress induced by reactive oxygen species (ROS) is promising treatment approach for pancreatic ductal adenocarcinoma (PDAC), which is typically insensitive to conventional chemotherapy. In this study, BxPC-3 pancreatic cancer cell membrane-coated upconversion nanoparticles/ZnxMn1-xS core-shell nanoparticles (abbreviated as BUC@ZMS) were developed for tumor-targeted cancer therapy via synergistically oxidative stress and overcoming glutathione (GSH) overexpression. Using a combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT), the BUC@ZMS core-shell nanoparticles were able to elicit the death of pancreatic cancer cells through the high production of ROS. Additionally, the BUC@ZMS core-shell nanoparticles could deplete intracellular GSH and increase the sensitivity of tumor cells to oxidative stress. The in vivo results indicated that BUC@ZMS nanoparticles can accumulate specifically in tumor locations and suppress PDAC without generating obvious toxicity. Thus, it was determined that the as-prepared core-shell nanoparticles would be a viable treatment option for solid malignancies.

Bi2-xMnxO3 Nanospheres Engaged Radiotherapy with Amplifying DNA Damage.

Radiotherapy efficacy was greatly limited by hypoxia and overexpression of glutathione (GSH) in the tumor microenvironment (TME), which maintained the immunosuppressive microenvironment and promoted DNA repair. In this work, 4T1 cell membrane-coated Bi2-xMnxO3 nanospheres have been achieved via a facile protocol, which showed enhanced therapeutic efficacy for a combination of radiotherapy and immunotherapy. Bi2-xMnxO3 nanospheres showed appreciable performance in generating O2 in situ and depleting GSH to amplify DNA damage and remodel the tumor immunosuppressive microenvironment, thus enhancing radiotherapy efficacy. Cancer cell membrane-coated Bi2-xMnxO3 nanospheres (T@BM) prolonged blood circulation time and enriched the accumulation of the materials in the tumor. Meanwhile, the released Mn2+ could activate STING pathway-induced immunotherapy, resulting in the immune infiltration of CD8+ T cells on in situ mammary tumors and the inhibition of pulmonary nodules. As a result, approximately 1.9-fold recruitment of CD8+ T cells and 4.0-fold transformation of mature DC cells were observed compared with the phosphate-buffered saline (PBS) group on mammary tumors (in situ). In particular, the number of pulmonary nodules significantly decreased and the proliferation of pulmonary metastatic lesions was substantially inhibited, which provided a longer survival period. Therefore, T@BM exhibited great potential for the treatment of 4T1 tumors in situ and lung metastasis.

A day-to-day management model improves patient compliance to treatment for Helicobacter pylori infection: a prospective, randomized controlled study.

BACKGROUND: The day-to-day (DTD) management model encourages patients to actively participate in their healthcare by setting goals. We determined the effectiveness of the DTD model in the treatment of Helicobacter pylori (H. pylori) infection, as compared with conventional outpatient education (OE). METHODS: We randomized 254 H. pylori-positive patients into a DTD group (127 patients) and an OE group (127 patients) prior to primary treatment with 14-day bismuth-containing quadruple therapy, including esomeprazole, amoxicillin, and clarithromycin. Both groups received consistent medication instructions. Patients in the DTD group recorded daily attendance after completing their daily medication plan from day 1 to day 14. The medication compliance, follow-up compliance, H. pylori eradication rates, and adverse events (AEs) were evaluated. RESULTS: In the modified intention-to-treat (MITT) and per-protocol (PP) analyses, the DTD group showed significantly higher medication compliance than the OE group (P = 0.001 and P = 0.031, respectively). Both the MITT and PP analyses showed significant differences in follow-up compliance (P < 0.001 and P = 0.003, respectively) and timing of the review urea breath test (P < 0.001 and P = 0.001, respectively) between the two groups. However, no significant differences were observed in the H. pylori eradication rates (95.8% vs. 93.8%, P = 0.529) in the PP analysis, or AEs incidence (25.4% vs. 28.3%, P = 0.603) between the two groups. CONCLUSION: This study demonstrated the novel application of the DTD model in the treatment of H. pylori infection, which enabled patients to develop habitual medication-taking behaviors without physician intervention.

Injectable Hydrogel Containing TiO Nanosheets for Synergistic Photothermal/Thermodynamic Therapy.

Tumors have become the biggest obstacle to human health, and there are various treatment methods at present. Photothermal therapy (PTT) is usually ineffective and does not inhibit tumor progression due to the inability of the lasers to penetrate deeply. Therefore, most existing studies chose a 1064 nm laser with stronger penetrating power; meanwhile, studies have shown that the inclusion of harmful free radicals can significantly improve the antitumor efficacy. Herein, TiO nanosheets (NSs) were creatively prepared and encapsulated with an alkyl radical generator {2,2'-azobis[2-(2-imidazoline-2-yl)propane] dihydrochloride, [AIPH]} in sodium alginate (ALG) hydrogel for effective tumor killing by PTT and pairing with dangerous free radicals. TiO NSs were obtained by the liquid-phase exfoliation method, together with AIPH, which were in situ coencapsulated multifunctional hydrogels formed by the combination of Ca2+ and ALG. This ALG hydrogel could enrich TiO NSs and AIPH at the tumor site for a long time, and through the excellent photothermal properties of TiO NSs, AIPH could slowly and effectively generate alkyl radicals at the tumor site, which, in turn, gave it a better antitumor effect compared with that of TiO NSs in the deep hypoxic environment of the tumor. The AIPH + TiO + ALG hydrogel has distinctive anticancer capabilities based on the results of both in vivo and in vitro experiments. This material also has good biosafety. By combining PTT and free radical treatment, this work provides a novel therapeutic method to achieve oxygen-independent free radical production and enhance therapeutic efficacy.