Building covalent crosslinks of carboxymethyl konjac glucomannan with boronic ester bonds for fabricating multimodal hydrogel sensor.

As the derivative of konjac glucomannan (KGM), carboxymethyl konjac glucomannan (CMK) has attracted increasing attention in the polysaccharide hydrogel fields with the aim of improving the performance related to drug delivery and release. In this study, we prepared a CMK-based hydrogel with dual characteristic crosslinks, and unlocked new applications of this type of hydrogel in soft sensor fields. CMK and poly (vinyl alcohol) were used as substrates, and physical crosslinks were constructed via the freeze-thawing treatments and covalent crosslinks were built via the boronic ester bonding. As-prepared hydrogel possessed significantly improved mechanical performance because the boronic ester bonding, on the one hand, well associated the two kinds of polymer chains, and on the other hand, played the role of 'sacrificial crosslinks'. Furthermore, the occurrence of dynamic boronic ester bonding gave the hydrogel strain- and temperature-sensitive ionic conductivity, and therefore, the hydrogels could be used to identify human motions and as-resulted environmental temperature alterations, and worked well in various scenarios. This work activates new application of CMK in the multimodal sensing field, and also proposes an intriguing way of building multiple crosslinks in the KGM derivative-based hydrogels.

Analysis of risk factors for complications in echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation.

BACKGROUND: The feasibility of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for the treatment of hypertrophic obstructive cardiomyopathy (HOCM) has been previously reported. However, limited investigation has been conducted regarding the complications associated with this procedure. OBJECTIVE: This study aims to analyze the risk factors affecting the occurrence of complications during PIMSRA, such as pericardial effusion, ventricular premature beats, and interventricular septal perforation. In this study, the optimal cut-off values for these risk factors are also explored, and corresponding strategies for prevention are proposed. METHODS: A total of 101 patients diagnosed with HOCM who underwent the PIMSRA procedure from 2021 to 2022 were included in this retrospective analysis. Patients were classified into subgroups with or without complications based on procedural records. Univariate and multivariate regression analyses were conducted to identify independent risk factors for complications during the PIMSRA procedure. RESULTS: There were 48 patients with complications and 53 patients without complications. The heart rate at the start of the procedure and the maximum left ventricular outflow tract gradient (LVOTG) were independent risk factors related to PIMSRA complications. The optimal cut-off values for predicting complication occurrence were a heart rate > 49 bpm at the start of the procedure (OR: 3.79, 95% CI: 1.64-8.78, p = 0.002) and a maximum LVOTG > 92 mmHg (OR: 2.57, 95% CI: 1.15-5.75, p = 0.022), respectively. CONCLUSIONS: The occurrence of PIMSRA complications is primarily associated with the heart rate at the start of the procedure and the maximum LVOTG. It is recommended to establish a comprehensive control plan to minimize the risk of complications during PIMSRA procedures.

Smartwatch-Detected Arrhythmias in Patients After Transcatheter Aortic Valve Replacement (TAVR): Analysis of the SMART TAVR Trial.

BACKGROUND: There are limited data available on the development of arrhythmias in patients at risk of high-degree atrioventricular block (HAVB) or complete heart block (CHB) following transcatheter aortic valve replacement (TAVR). OBJECTIVE: This study aimed to explore the incidence and evolution of arrhythmias by monitoring patients at risk of HAVB or CHB after TAVR using smartwatches. METHODS: We analyzed 188 consecutive patients in the prospective SMART TAVR (smartwatch-facilitated early discharge in patients undergoing TAVR) trial. Patients were divided into 2 groups according to the risk of HAVB or CHB. Patients were required to trigger a single-lead electrocardiogram (ECG) recording and send it to the Heart Health App via their smartphone. Physicians in the central ECG core lab would then analyze the ECG. The incidence and timing of arrhythmias and pacemaker implantation within a 30-day follow-up were compared. All arrhythmic events were adjudicated in a central ECG core lab. RESULTS: The mean age of the patients was 73.1 (SD 7.3) years, of whom 105 (55.9%) were men. The mean discharge day after TAVR was 2.0 (SD 1.8) days. There were no statistically significant changes in the evolution of atrial fibrillation or atrial flutter, Mobitz I, Mobitz II, and third-degree atrial ventricular block over time in the first month after TAVR. The incidence of the left bundle branch block (LBBB) increased in the first week and decreased in the subsequent 3 weeks significantly (P<.001). Patients at higher risk of HAVB or CHB received more pacemaker implantation after discharge (n=8, 9.6% vs n=2, 1.9%; P=.04). The incidence of LBBB was higher in the group with higher HAVB or CHB risk (n=47, 56.6% vs n=34, 32.4%; P=.001). The independent predictors for pacemaker implantation were age, baseline atrial fibrillation, baseline right bundle branch block, Mobitz II, and third-degree atrioventricular block detected by the smartwatch. CONCLUSIONS: Except for LBBB, no change in arrhythmias was observed over time in the first month after TAVR. A higher incidence of pacemaker implantation after discharge was observed in patients at risk of HAVB or CHB. However, Mobitz II and third-degree atrioventricular block detected by the smartwatch during follow-ups were more valuable indicators to predict pacemaker implantation after discharge from the index TAVR. TRIAL REGISTRATION: ClinicalTrials.gov NCT04454177; https://clinicaltrials.gov/study/NCT04454177.

A modified Carpentier classification in transcatheter edge-to-edge repair for mitral regurgitation.

Mitral regurgitation (MR) is the most common heart valve disease, and transcatheter edge-to-edge repair (TEER) has been recommended as a therapy for severe MR patients by guidelines. The classic Carpentier classification used to guide surgical mitral valve repair but is inadequate for mitral TEER (M-TEER). We herein proposed a new modified Carpentier classification named after "type + segment," which is suitable for M-TEER. We shared our strategies in M-TEER procedure for screening and performing the M-TEER according to the new modified Carpentier classification.

An Automatic Coronary Microvascular Dysfunction Classification Method Based on Hybrid ECG Features and Expert Features.

OBJECTIVE: In recent years, the early diagnosis and treatment of coronary microvascular dysfunction (CMD) have become crucial for preventing coronary heart disease. This paper aims to develop a computer-assisted autonomous diagnosis method for CMD by using ECG features and expert features. APPROACH: Clinical electrocardiogram (ECG), myocardial contrast echocardiography (MCE), and coronary angiography (CAG) are used in our method. Firstly, morphological features, temporal features, and T-wave features of ECG are extracted by multi-channel residual network with BiLSTM (MCResnet-BiLSTM) model and the multi-source T-wave features (MTF) extraction model, respectively. And these features are fused to form ECG features. In addition, the CFR[Formula: see text] is calculated based on the parameters related to the MCE at rest and stress state, and the Angio-IMR is calculated based on CAG. The combination of CFR[Formula: see text] and Angio-IMR is termed as expert features. Furthermore, the hybrid features, fused from the ECG features and the expert features, are input into the multilayer perceptron to implement the identification of CMD. And the weighted sum of the softmax loss and center loss is used as the total loss function for training the classification model, which optimizes the classification ability of the model. RESULT: The proposed method achieved 93.36% accuracy, 94.46% specificity, 92.10% sensitivity, 95.89% precision, and 93.95% F1 score on the clinical dataset of the Second Affiliated Hospital of Zhejiang University. CONCLUSION: The proposed method accurately extracts global ECG features, combines them with expert features to obtain hybrid features, and uses weighted loss to significantly improve diagnostic accuracy. It provides a novel and practical method for the clinical diagnosis of CMD.

Comparison of downsizing strategy (HANGZHOU Solution) and standard annulus sizing strategy in type 0 bicuspid aortic stenosis patients undergoing transcatheter aortic valve replacement: Rationale and design of a randomized clinical trial.

BACKGROUND: There has not been a consensus on the prothesis sizing strategy in type 0 bicuspid aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR). Modifications to standard annular sizing strategies might be required due to the distinct anatomical characteristics. We have devised a downsizing strategy for TAVR using a self-expanding valve specifically for patients with type 0 bicuspid AS. The primary aim of this study is to compare the safety and efficacy of downsizing strategy with the Standard Annulus Sizing Strategy in TAVR for patients with type 0 bicuspid AS. TRIAL DESIGN: It is a prospective, multi-center, superiority, single-blinded, randomized controlled trial comparing the Down Sizing and Standard Annulus Sizing Strategy in patients with type 0 bicuspid aortic stenosis undergoing transcatheter aortic valve replacement. Eligible participants will include patients with severe type 0 bicuspid AS, as defined by criteria such as mean gradient across aortic valve ≥40 mmHg, peak aortic jet velocity ≥4.0 m/s, aortic valve area (AVA) ≤1.0 cm², or AVA index ≤0.6 cm2/m2. These patients will be randomly assigned, in a 1:1 ratio, to either the Down Sizing Strategy group or the Standard Sizing Strategy group. In the Down Sizing Strategy group, a valve one size smaller will be implanted if the "waist sign" manifests along with less than mild regurgitation during balloon pre-dilatation. The primary end point of the study is a composite of VARC-3 defined device success, absence of both permanent pacemaker implantation due to high-degree atrioventricular block and new-onset complete left bundle branch block. CONCLUSION: This study will compare the safety and efficacy of Down Sizing Strategy with the Standard Annulus Sizing Strategy and provide valuable insights into the optimal approach for sizing in TAVR patients with type 0 bicuspid AS. We hypothesize that the Down Sizing Strategy will demonstrate superiority when compared to the Standard Annulus Sizing Strategy. (Down Sizing Strategy (HANGZHOU Solution) vs Standard Sizing Strategy TAVR in Bicuspid Aortic Stenosis (Type 0) (TAILOR-TAVR), NCT05511792).

Structural and functional alteration of the gut microbiota in elderly patients with hyperlipidemia.

Objective: To investigate the structure, composition, and functions of the gut microbiota in elderly patients with hyperlipidemia. Methods: Sixteen older patients diagnosed with hyperlipidemia (M group) and 10 healthy, age-matched normal volunteers (N group) were included. These groups were further subdivided by sex into the male normal (NM, n = 5), female normal (NF, n = 5), male hyperlipidemia (MM, n = 8), and female hyperlipidemia (MF, n = 8) subgroups. Stool samples were collected for high-throughput sequencing of 16S rRNA genes. Blood samples were collected for clinical biochemical index testing. Results: Alpha- and beta-diversity analyses revealed that the structure and composition of the gut microbiota were significantly different between the M and N groups. The relative abundances of Bacteroides, Parabacteroides, Blautia, Peptococcus, and Bifidobacterium were significantly decreased, while those of Lactobacillus, Helicobacter, and Desulfovibrio were significantly higher in the M group. There were also significant sex-related differences in microbial structure between the NM and NF groups, and between the MM and MF groups. Through functional prediction with PICRUSt 2, we observed distinct between-group variations in metabolic pathways associated with the gut microbiota and their impact on the functionality of the nervous system. Pearson's correlation coefficient was used as a distance metric to build co-abundance networks. A hypergeometric test was used to detect taxonomies with significant enrichment in specific clusters. We speculated that modules with Muribaculaceae and Lachnospiraceae as the core microbes play an important ecological role in the intestinal microbiota of the M group. The relative intestinal abundances of Agathobacter and Faecalibacterium in the M group were positively correlated with serum triglyceride and low-density lipoprotein levels, while the relative abundance of Bifidobacterium was negatively correlated with the serum lipoprotein a level.

Chitin nanocrystals-stabilized emulsion as template for fabricating injectable suspension containing polylactide hollow microspheres.

One of the promising applications of rod-like chitin nanocrystals (ChNCs) is the use as particle emulsifier to develop Pickering emulsions. We reported a ChNC-stabilized oil-in-water emulsion system, and developed a Pickering emulsion-templated method to prepare polylactide (PLA) hollow microspheres here. The results showed that both non-modified ChNCs and acetylated ChNCs could well emulsify the dichloromethane (DCM) solution of PLA-in-aqueous mannitol solution systems, forming very stable emulsions. At the same oil-to-water ratios and ChNC loadings, the emulsion stability was improved with increasing acetylation levels of ChNCs, accompanied by reduced size of droplets. Through the solvent evaporation, the PLA hollow microspheres were templated successfully, and the surface structure was also strongly dependent on the acetylation level of ChNCs. At a low level of acetylation, the single-hole or multi-hole surface structure formed, which was attributed to the out-diffusion of DCM caused by the solvent extraction and evaporation. These surface defects decreased with increased acetylation levels of ChNCs. Moreover, the aqueous suspension with as-obtained PLA microspheres revealed shear-thinning property and good biocompatibility, thereby had promising application as injectable fillers. This work can provide useful information around tuning surface structures of the Pickering emulsion-templated polymer hollow microspheres by regulating acetylation level of ChNCs.

Three new pterosins from Pteris semipinnata.

Three new pterosins, named as semipterosin A (1), B (2) and C (3), together with 11 known pterosins (4-14), were isolated from the aerial parts of Pteris semipinnata. Their structures were elucidated by HRESI-MS, NMR spectral data, CD and literature comparisons. Three new pterosins were assessed for their anti-inflammatory activity. Compounds 1-3 inhibited the NF-kB induction by 40.7%, 61.9% and 34.0%, respectively. This is the first report of the isolation of compounds 6-14 from this plant.

Cerium-Luteolin Nanocomplexes in Managing Inflammation-Related Diseases by Antioxidant and Immunoregulation.

Oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) production and the antioxidant defense system, plays a pivotal role in inflammation-related diseases. Excessive ROS levels can induce cellular damage and impair normal physiological functions, triggering the release of inflammatory mediators and exacerbating the inflammatory response, ultimately leading to irreversible tissue damage. In this study, we synthesized cerium ion-luteolin nanocomplexes (CeLutNCs) by coordinating Ce ions with the natural product luteolin, aiming to develop a therapeutic agent with excellent antioxidant and immunoregulation properties for ROS-related inflammation treatment. In vitro experiments demonstrated that the prepared CeLutNCs effectively scavenged excess ROS, prevented cell apoptosis, down-regulated levels of important inflammatory cytokines, regulated the response of inflammatory macrophages, and suppressed the activation of the nuclear factor-κ-gene binding (NF-κB) pathway. In an acute kidney injury (AKI) animal model, CeLutNCs exhibited significant efficacy in improving kidney function, repairing damaged renal tissue, and reducing oxidative stress, inflammatory response, and cellular apoptosis. Moreover, the therapeutic potential of CeLutNCs in an acute lung injury (ALI) model was confirmed through the assessment of inflammatory responses and histopathological studies. This study emphasizes the effectiveness of these metal-natural product coordination nanocomplexes as a promising therapeutic approach for preventing AKI and other diseases associated with oxidative stress.

Ultralight Electrolyte with Protective Encapsulation Solvation Structure Enables Hybrid Sulfur-Based Primary Batteries Exceeding 660 Wh/kg.

An electrochemical couple of lithium and sulfur possesses the highest theoretical energy density (>2600 Wh/kg) at the material level. However, disappointingly, it is out of place in primary batteries due to its low accessible energy density at the cell level (≤500 Wh/kg) and poor storage performance. Herein, a low-density methyl tert-butyl ether was tailored for an ultralight electrolyte (0.837 g/mL) with a protective encapsulation solvation structure which reduced electrolyte weight (23.1%), increased the utilization of capacity (38.1%), and simultaneously forfended self-discharge. Furthermore, active fluorinated graphite partially replaced inactive carbon to construct a hybrid sulfur-based cathode to bring the potential energy density into full play. Our demonstrated pouch cell achieved an incredible energy density of 661 Wh/kg with a negligible self-discharge rate based on the above innovations. Our work is anticipated to provide a new direction to realize the practicality of lithium-sulfur primary batteries.

Mechanical study of alisol B 23-acetate on methionine and choline deficient diet-induced nonalcoholic steatohepatitis based on untargeted metabolomics.

Alisol B 23-acetate (AB23A) has been demonstrated to have beneficial effects on nonalcoholic steatohepatitis (NASH). However, the mechanisms of AB23A on NASH remain unclear. This study aimed to investigate the mechanisms underlying the metabolic regulatory effects of AB23A on NASH. We used AB23A to treat mice with NASH, which was induced by a methionine and choline deficient (MCD) diet. We initially investigated therapeutic effect and resistance to oxidation and inflammation of AB23A on NASH. Subsequently, we performed untargeted metabolomic analyses and relative validation assessments to evaluate the metabolic regulatory effects of AB23A. AB23A reduced lipid accumulation, ameliorated oxidative stress and decreased pro-inflammatory cytokines in the liver. Untargeted metabolomic analysis found that AB23A altered the metabolites of liver. A total of 55 differential metabolites and three common changed pathways were screened among the control, model and AB23A treatment groups. Further tests validated the effects of AB23A on modulating common changed pathway-involved factors. AB23A treatment can ameliorate NASH by inhibiting oxidative stress and inflammation. The mechanism of AB23A on NASH may be related to the regulation of alanine, aspartate and glutamate metabolism, d-glutamine and d-glutamate metabolism, and arginine biosynthesis pathways.

Effects of neoadjuvant stereotactic body radiotherapy plus adebrelimab and chemotherapy for triple-negative breast cancer: A pilot study.

Background: Emerging data have supported the immunostimulatory role of radiotherapy, which could exert a synergistic effect with immune checkpoint inhibitors (ICIs). With proven effective but suboptimal effect of ICI and chemotherapy in triple-negative breast cancer (TNBC), we designed a pilot study to explore the efficacy and safety of neoadjuvant stereotactic body radiotherapy (SBRT) plus adebrelimab and chemotherapy in TNBC patients. Methods: Treatment-naïve TNBC patients received two cycles of intravenous adebrelimab (20 mg/kg, every 3 weeks), and SBRT (24 Gy/3 f, every other day) started at the second cycle, then followed by six cycles of adebrelimab plus nab-paclitaxel (125 mg/m² on days 1 and 8) and carboplatin (area under the curve 6 mg/mL per min on day 1) every 3 weeks. The surgery was performed within 3-5 weeks after the end of neoadjuvant therapy. Primary endpoint was pathological complete response (pCR, ypT0/is ypN0). Secondary endpoints included objective response rate (ORR), residual cancer burden (RCB) 0-I, and safety. Results: 13 patients were enrolled and received at least one dose of therapy. 10 (76.9%) patients completed SBRT and were included in efficacy analysis. 90% (9/10) of patients achieved pCR, both RCB 0-I and ORR reached 100% with three patients achieved complete remission. Adverse events (AEs) of all-grade and grade 3-4 occurred in 92.3% and 53.8%, respectively. One (7.7%) patient had treatment-related serious AEs. No radiation-related dermatitis or death occurred. Conclusions: Adding SBRT to adebrelimab and neoadjuvant chemotherapy led to a substantial proportion of pCR with acceptable toxicities, supporting further exploration of this combination in TNBC patients. Funding: None. Clinical trial number: NCT05132790.

Crocin Ameliorates Diabetic Nephropathy through Regulating Metabolism, CYP4A11/PPARγ, and TGF-ß/Smad Pathways in Mice.

INTRODUCTION: Crocin is one of the main components of Crocus sativus L. and can alleviate oxidative stress and inflammation in diabetic nephropathy (DN). However, the specific mechanism by which crocin treats DN still needs to be further elucidated. METHOD: In the present study, a mouse model of DN was first established to investigate the therapeutic effect of crocin on DN mice. Subsequently, non-targeted metabolomics techniques were used to analyze the mechanisms of action of crocin in the treatment of DN. The effects of crocin on CYP4A11/PPARγ and TGF-ß/Smad pathway were also investigated. RESULT: Results showed that crocin exhibited significant therapeutic and anti-inflammatory, and anti-oxidative effects on DN mice. In addition, the non-targeted metabolomics results indicated that crocin treatment affected several metabolites in kidney. These metabolites were mainly associated with biotin metabolism, riboflavin metabolism, and arachidonic acid metabolism. Furthermore, crocin treatment upregulated the decreased levels of CYP4A11 and phosphorylated PPARγ, and reduced the increased levels of TGF-ß1 and phosphorylated Smad2/3 in the kidneys of DN mice. CONCLUSION: In conclusion, our study validated the considerable therapeutic, anti-inflammatory, and antioxidative impacts of crocin on DN mice. The mechanism of crocin treatment may be related to the regulation of biotin riboflavin and arachidonic acid metabolism, the activation of CYP4A11/PPARγ pathway, and the inhibition of TGF-ß/Smad pathway in the kidney.

Enterococcus faecium R-026 combined with Bacillus subtilis R-179 alleviate hypercholesterolemia and modulate the gut microbiota in C57BL/6 mice.

Probiotics have been demonstrated to lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in individuals with mild hypercholesterolemia. Our previous study found that intervention with Bacillus subtilis R-179 and Enterococcus faecium R-026, well-known probiotics, improved obesity-associated dyslipidemia through ameliorating the gut microbiota, but similar studies on hypercholesterolemia have not been reported to date. Here, we investigated the therapeutic effect of live combined B. subtilis R-179 and E. faecium R-026 (LCBE) in a C57BL/6 mouse model of hypercholesterolemia. A total of 40 mice were administered with a high-cholesterol diet (containing 1.2% cholesterol) to establish a state of hypercholesterolemia for 4 weeks. Then, mice were divided into one model group (group M) and three treatment groups (n = 10 per group), which were administered with LCBE at 0.023 g/mouse/day (group L) or 0.230 g/mouse/day (group H), or atorvastatin 0.010 g/kg/day (group A), for 5 weeks while on a high-cholesterol diet. LCBE at high doses significantly alleviated the symptoms of group M and reduced serum TC, LDL-C, and lipopolysaccharide (LPS). LCBE improved liver steatosis and adipocyte enlargement caused by a high-cholesterol diet. In addition, the administration of LCBE regulated the change in gut microbiota and diversity (Shannon index). Compared with group M, the relative abundance of Actinobacteriota, Colidextribacter, and Dubosiella dramatically decreased in the treatment groups, which were positively correlated with serum TC and LPS. These findings indicated that the mechanism of action of LCBE in treating hypercholesterolemia may be modulation of the gut microbiota. In conclusion, LCBE ameliorated lipid accumulation, reduced inflammation, and alleviated the gut microbiota imbalance in hypercholesterolemic mice. These findings support the probiotic role of LCBE as a clinical candidate for the treatment of hypercholesterolemia.

Predictive models for sepsis in children with Staphylococcus aureus bloodstream infections: a retrospective cohort study.

BACKGROUND: The presence of Staphylococcus aureus in the bloodstream can lead to the development of sepsis; however, the severity and risk factors of the systemic inflammatory response to Staphylococcus aureus bloodstream infections were unclear. This study is aimed to build a model to predict the risk of sepsis in children with Staphylococcus aureus bloodstream infections. METHODS: A retrospective analysis of hospitalized pediatric patients diagnosed with Staphylococcus aureus bloodstream infections was performed between January 2013 and December 2019. Each patient was assessed using the pediatric version of the Sequential Organ Failure Assessment score (pSOFA) within 24 h of blood culture collection. A nomogram based on logistic regression models was constructed to predict the risk factors for sepsis in children with Staphylococcus aureus bloodstream infections. It was validated using the area under the receiver-operating characteristic curve (AUC). RESULTS: Of the 94 patients included in the study, 35 cases (37.2%) developed sepsis. The pSOFA scores ranged from 0 to 8, with 35 patients having a pSOFA score of ≥ 2. Six children (6.4%) died within 30 days, who were all from the sepsis group and had different pSOFA scores. The most common organs involved in sepsis in children with staphylococcal bloodstream infections were the neurologic system (68.6%), respiratory system (48.6%), and coagulation system (45.7%). Hospital-acquired infections (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.3-7.2), implanted catheters (aOR, 10.4; 95% CI, 3.8-28.4), procalcitonin level ≥ 1.7 ng/mL (aOR, 15.4; 95% CI, 2.7-87.1), and underlying diseases, especially gastrointestinal malformations (aOR, 14.0; 95% CI, 2.9-66.7) were associated with Staphylococcus aureus sepsis. However, methicillin-resistant Staphylococcus aureus infection was not a risk factor for sepsis. The nomogram had high predictive accuracy for the estimation of sepsis risk, with an AUC of 0.85. CONCLUSIONS: We developed a predictive model for sepsis in children with Staphylococcus aureus infection.

Dalpiciclib and pyrotinib in women with HER2-positive advanced breast cancer: a single-arm phase II trial.

CDK4/6 inhibitors have shown a synergistic effect with anti-HER2 therapy in hormone receptor (HR)-positive and HER2-positive breast cancer (BC). In this phase 2 study (NCT04293276), we aim to evaluate a dual-oral regimen of CDK4/6 inhibitor dalpiciclib combined with HER2 tyrosine kinase inhibitor pyrotinib as front-line treatment in women with HER2-positive advanced BC (n = 41) including those with HR-negative disease. The primary endpoint is the objective response rate, and secondary endpoints include progression-free survival (PFS), overall survival (OS), and safety. With a median follow-up of 25.9 months, 70% (28/40) of assessable patients have a confirmed objective response, meeting the primary endpoint. The median PFS is 11.0 months (95% CI = 7.3-19.3), and OS data are not mature. The most common grade 3 or 4 treatment-related adverse events (AEs) are decreased white blood cell count (68.3%), decreased neutrophil count (65.9%), and diarrhea (22.0%). Most AEs are manageable, and no treatment-related deaths occur. These findings suggest that this combination may have promising activity and manageable toxicity. Further investigation is needed.

The gut microbiome: an important factor influencing therapy for pediatric acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most prevalent form of pediatric leukemia. The gut microbiome (GM) is crucial for proper nutrition, immunity, and biological conflict. Since the relationship between ALL and GM is bidirectional, ALL occurrence and treatment are closely related to GM destruction and the development of impaired immunity. Studies have discovered significant GM alterations in patients with ALL, including decreased diversity, that are likely directly caused by the development of ALL. Chemotherapy, antibiotic therapy, and hematopoietic stem cell transplantation (HSCT) are the mainstays of treatment for pediatric ALL. These approaches affect the composition, diversity, and abundance of intestinal microorganisms, which in turn affects therapeutic efficiency and can cause a variety of complications. Modulating the GM can aid the recovery of patients with ALL. This article discusses the various treatment modalities for pediatric ALL and their corresponding effects on the GM, as well as the changes in the GM that occur in children with ALL from diagnosis to treatment. Gaining a greater understanding of the link between ALL and the GM is expected to help improve treatment for pediatric ALL in the future.

Beer-gut microbiome alliance: a discussion of beer-mediated immunomodulation via the gut microbiome.

As a long-established fermented beverage, beer is rich in many essential amino acids, vitamins, trace elements, and bioactive substances that are involved in the regulation of many human physiological functions. The polyphenols in the malt and hops of beer are also important active compounds that interact in both directions with the gut microbiome. This review summarizes the mechanisms by which polyphenols, fiber, and other beneficial components of beer are fermentatively broken down by the intestinal microbiome to initiate the mucosal immune barrier and thus participate in immune regulation. Beer degradation products have anti-inflammatory, anticoagulant, antioxidant, and glucolipid metabolism-modulating potential. We have categorized and summarized reported data on changes in disease indicators and in vivo gut microbiota abundance following alcoholic and non-alcoholic beer consumption. The positive effects of bioactive substances in beer in cancer prevention, reduction of cardiovascular events, and modulation of metabolic syndrome make it one of the candidates for microecological modulators.

San-Huang-Yi-Shen capsule ameliorates diabetic nephropathy in mice through inhibiting ferroptosis.

Diabetic nephropathy (DN) is one of the main complications of diabetes. However, effective therapy to block or slow down the progression of DN is still lacking. San-Huang-Yi-Shen capsule (SHYS) has been shown to significantly improve renal function and delay the progression of DN. However, the mechanism of SHYS on DN is still unclear. In this study, we established a mouse model of DN. Then, we investigated the anti-ferroptotic effects of SHYS including the reduction of iron overload and the activation of cystine/GSH/GPX4 axis. Finally, we used a GPX4 inhibitor (RSL3) and ferroptosis inhibitor (ferrostatin-1) to determine whether SHYS ameliorates DN through inhibiting ferroptosis. The results showed that SHYS treatment was effective for mice with DN in terms of improving renal function, and reducing inflammation and oxidative stress. Besides, SHYS treatment reduced iron overload and upregulated the expression of cystine/GSH/GPX4 axis-related factors in kidney. Moreover, SHYS exhibited similar therapeutic effect on DN as ferrostatin-1, RSL3 could abolish the therapeutic and anti- ferroptotic effects of SHYS on DN. In conclusion, SHYS can be used to treat mice with DN. Furthermore, SHYS could inhibit ferroptosis in DN through reducing iron overload and upregulating the expression of cystine/GSH/GPX4 axis.