Effects of industrial-scale pickling processes on the dynamic changes in the physicochemical indicators and microbial diversities of Yacai.

The effects of dry-salted and salt-fermented processing on the physicochemical characteristics and microbial communities of Yacai were systematically investigated. The results showed that the contents of total acid, amino acid nitrogen (AAN) and nitrite in the final products of dry-salted Yacai were greater than those in salt-fermented Yacai. Lactic acid was the dominant organic acid in the two types of Yacai. Dry-salted processing is more conducive to forming a high-quality reddish-brown color. During whole pickling process, the microbial diversity of dry-salted Yacai was higher than that of salt-fermented Yacai, particularly in the early and middle stages of fermentation. For dry-salted Yacai, 8 bacteria (Natribacillus, Chromohalobacter, Marinococcus, Lentibacillus, Nesterenkonia, Gracilibacillus, Oceanobacillus and Tetragenococcus) and 1 fungus (Zygosaccharomyces) showed a significant positive correlation with AAN. For salt-fermented Yacai, 8 bacteria (Gracilibacillus, Alkalibacillus, Oceanobacillus, Virgibacillus, Lentibacillus, Salibacterium, Chromohalobacter and Tetragenococcus) and 3 fungi (Zygosaccharomyces, Millerozyma, and Wickerhamomyces) exhibited significant positive correlations with AAN.

Machine learning-based CT radiomics enhances bladder cancer staging predictions: A comparative study of clinical, radiomics, and combined models.

BACKGROUND: Predicting the accurate preoperative staging of bladder cancer (BLCA), which markedly affects treatment decisions and patient outcomes, using traditional clinical parameters is challenging. Nevertheless, emerging studies in radiomics, especially machine learning-based computed tomography (CT) image-based radiomics, hold promise in improving stage prediction accuracy in various tumors. However, the comparative performance and clinical utility of models for BLCA are under investigation. PURPOSE: We aimed to investigate the application value of machine learning-based CT radiomics in preoperative staging prediction by comparing the performance of clinical, radiomics, and clinical-radiomics combined models. METHODS: A retrospective cohort of 105 patients with initial BLCA was randomized into training (70%) and testing (30%) cohorts. Radiomics features were extracted from CT images using the optimal feature filter, followed by the application of the least absolute shrinkage and selection operator algorithm for optimum feature selection. Furthermore, machine learning algorithms were used to establish a radiomics model within the training cohort. Independent risk factors for muscle-invasive BLCA (MIBC) obtained by multivariate logistic regression (LR) analysis were separately used to construct a clinical model. For a clinical-radiomics fusion model, radiomics features were combined with clinical parameters. Performance was evaluated based on receiver operating characteristic curves, calibration curves, decision curve analysis (DCA), and standard performance metrics. RESULTS: Patients exhibited a significantly higher age (p = 0.029), larger tumor size (p = 0.01), and an increased neutrophil-to-lymphocyte ratio (NLR; p = 0.045) in the MIBC group than in the NMIBC group. LR analysis revealed age (p = 0.026), tumor size (p = 0.007), and NLR (p = 0.019) as significant predictors for constructing the clinical model. In the testing cohort, the radiomics model, which used an Support Vector Machine classifier, achieved the highest area under the curve (AUC) value of 0.857. The clinical-radiomics model outperformed the remaining two models, with AUC values of 0.958 and 0.893 in the training and testing cohorts, respectively. DeLong's test indicated significant differences between the three models. Calibration curves showed good agreement, and DCA confirmed the superior clinical utility of the clinical-radiomics model. CONCLUSIONS: Machine learning-based CT radiomics combined with clinical parameters was a promising approach in staging BLCA accurately, which outperformed the individual models. Integrating radiomics features with clinical information holds the potential to improve personalized treatment planning and patient outcomes in BLCA.

Synthetic macrolides overcoming MLSBK-resistant pathogens.

Conventional macrolide-lincosamide-streptogramin B-ketolide (MLSBK) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLSBK in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties. Our effort led to the discovery of two potent compounds, MCX-219 and MCX-190, demonstrating enhanced antibacterial efficacy against a broad spectrum of formidable pathogens, including A2058-methylated Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and notably, the clinical Mycoplasma pneumoniae isolates harboring A2058G mutations which are implicated in the recent pneumonia outbreak in China. Mechanistic studies reveal that the modified quinolone moiety of MCX-190 establishes a distinctive secondary binding site within the nascent peptide exit tunnel. Structure-activity relationship analysis underscores the importance of this secondary binding, maintained by a sandwich-like π-π stacking interaction and a water-magnesium bridge, for effective engagement with A2058-methylated ribosomes rather than topoisomerases targeted by quinolone antibiotics. Our findings not only highlight MCX-219 and MCX-190 as promising candidates for next-generation MLSBK antibiotics to combat antibiotic resistance, but also pave the way for the future rational design of the class of MLSBK antibiotics, offering a strategic framework to overcome the challenges posed by escalating antibiotic resistance.

Preoperative prediction of histopathological grading in patients with chondrosarcoma using MRI-based radiomics with semantic features.

BACKGROUND: Distinguishing high-grade from low-grade chondrosarcoma is extremely vital not only for guiding the development of personalized surgical treatment but also for predicting the prognosis of patients. We aimed to establish and validate a magnetic resonance imaging (MRI)-based nomogram for predicting preoperative grading in patients with chondrosarcoma. METHODS: Approximately 114 patients (60 and 54 cases with high-grade and low-grade chondrosarcoma, respectively) were recruited for this retrospective study. All patients were treated via surgery and histopathologically proven, and they were randomly divided into training (n = 80) and validation (n = 34) sets at a ratio of 7:3. Next, radiomics features were extracted from two sequences using the least absolute shrinkage and selection operator (LASSO) algorithms. The rad-scores were calculated and then subjected to logistic regression to develop a radiomics model. A nomogram combining independent predictive semantic features with radiomic by using multivariate logistic regression was established. The performance of each model was assessed by the receiver operating characteristic (ROC) curve analysis and the area under the curve, while clinical efficacy was evaluated via decision curve analysis (DCA). RESULTS: Ultimately, six optimal radiomics signatures were extracted from T1-weighted imaging (T1WI) and T2-weighted imaging with fat suppression (T2WI-FS) sequences to develop the radiomics model. Tumour cartilage abundance, which emerged as an independent predictor, was significantly related to chondrosarcoma grading (p < 0.05). The AUC values of the radiomics model were 0.85 (95% CI, 0.76 to 0.95) in the training sets, and the corresponding AUC values in the validation sets were 0.82 (95% CI, 0.65 to 0.98), which were far superior to the clinical model AUC values of 0.68 (95% CI, 0.58 to 0.79) in the training sets and 0.72 (95% CI, 0.57 to 0.87) in the validation sets. The nomogram demonstrated good performance in the preoperative distinction of chondrosarcoma. The DCA analysis revealed that the nomogram model had a markedly higher clinical usefulness in predicting chondrosarcoma grading preoperatively than either the rad-score or clinical model alone. CONCLUSION: The nomogram based on MRI radiomics combined with optimal independent factors had better performance for the preoperative differentiation between low-grade and high-grade chondrosarcoma and has potential as a noninvasive preoperative tool for personalizing clinical plans.

A clinical-radiomics nomogram based on automated segmentation of chest CT to discriminate PRISm and COPD patients.

Purpose: It is vital to develop noninvasive approaches with high accuracy to discriminate the preserved ratio impaired spirometry (PRISm) group from the chronic obstructive pulmonary disease (COPD) groups. Radiomics has emerged as an image analysis technique. This study aims to develop and confirm the new radiomics-based noninvasive approach to discriminate these two groups. Methods: Totally 1066 subjects from 4 centers were included in this retrospective research, and classified into training, internal validation or external validation sets. The chest computed tomography (CT) images were segmented by the fully automated deep learning segmentation algorithm (Unet231) for radiomics feature extraction. We established the radiomics signature (Rad-score) using the least absolute shrinkage and selection operator algorithm, then conducted ten-fold cross-validation using the training set. Last, we constructed a radiomics signature by incorporating independent risk factors using the multivariate logistic regression model. Model performance was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses (DCA). Results: The Rad-score, including 15 radiomic features in whole-lung region, which was suitable for diffuse lung diseases, was demonstrated to be effective for discriminating between PRISm and COPD. Its diagnostic accuracy was improved through integrating Rad-score with a clinical model, and the area under the ROC (AUC) were 0.82(95 %CI 0.79-0.86), 0.77(95 %CI 0.72-0.83) and 0.841(95 %CI 0.78-0.91) for training, internal validation and external validation sets, respectively. As revealed by analysis, radiomics nomogram showed good fit and superior clinical utility. Conclusions: The present work constructed the new radiomics-based nomogram and verified its reliability for discriminating between PRISm and COPD.

Antibacterial Property and Mechanisms of Au@Ag Core-Shell Nanoparticles with Near-Infrared Absorption Against E. faecalis Infection of Dentin.

Background: Enterococcus faecalis (E. faecalis) is one of the main pathogens responsible for refractory root canal infections in the teeth and shows resistance against various antibacterial managements. Effective control of E. faecalis infection is a prerequisite for successful treatment of refractory apical periodontitis. This study aimed to analyze the antibacterial activity and mechanisms of Au@Ag nanoparticles (NPs) combined with photothermal therapy (PTT) against the original and Ag+-resistant E. faecalis. Methods: Au@AgNPs with optimal shell thicknesses were synthesized and characterized. The antibacterial activity of Au@AgNPs with PTT against the original or Ag+-resistant E. faecalis was evaluated, and the antibiofilm activity was tested on E. faecalis biofilm on the dentin of teeth. The potential antibacterial mechanisms of Au@AgNPs combined with PTT against E. faecalis have also been studied. Moreover, its influence on dentin microhardness and cytotoxicity was assessed. Results: This study revealed that Au@AgNPs combined with PTT showed enhanced antibacterial and antibiofilm effects, no negative effects on dentin microhardness, and low cytotoxicity toward human periodontal ligament cells (hPDLCs). Moreover, Au@AgNPs combined with PTT effectively inhibited the growth of Ag+-resistant E. faecalis. Its antibacterial effects may be exerted through the release of silver ions (Ag+), destruction of the cell membrane, production of reactive oxygen species (ROS) and inhibition of adenosine triphosphate (ATP) production. Hyperthermia generated by Au@AgNPs with PTT reduced membrane fluidity and enhanced Ag+ sensitivity by downregulating fabF expression. The upregulated expression of heat shock genes demonstrated that the Ag+ released from Au@AgNPs compromised the heat adaptation of E. faecalis. Conclusion: PTT significantly enhanced Ag+ sensitivity of the original and Ag+-resistant E. faecalis. Au@AgNPs combined with PTT may have the potential to be developed as a new antibacterial agent to control E. faecalis infections in teeth.

Widely targeted metabolomics and flavoromics reveal the effect of Wickerhamomyces anomalus fermentation on the volatile and nonvolatile metabolites of black garlic juice.

Black garlic has a variety of biological activities, but many consumers cannot accept it because of the garlic odor and the bitter taste. In this study, fermentation with yeast Wickerhamomyces anomalus was adopted to improve the flavor of black garlic juice. Although fermentation reduced antioxidant activities, the garlicky odor and bitter taste were weakened. Metabolomic analysis revealed 141 metabolites were significantly differentially regulated. The upregulated metabolites were mainly related to nucleotides, organic acids and their derivatives, while the downregulated metabolites were mainly related to amino acids, lipids and their derivatives. Flavoromics analysis revealed that 137 metabolites were significantly differentially regulated, particularly garlicky and pungent volatiles were significantly downregulated. Correlation analysis indicated that esters are most closely related to nonvolatile metabolites, and lipids degradation was significantly correlated with volatiles. The results indicated that W. anomalus fermentation is an effective strategy to improve the flavor of black garlic juice.

Examining the impact of permissibility hypercapnia on postoperative delirium among elderly patients undergoing thoracoscopic-laparoscopic esophagectomy: A single-center investigative study.

OBJECTIVE: This study explores how permissive hypercapnia, a key aspect of lung protective ventilation, impacts postoperative delirium in elderly patients following thoracic surgery. METHODS: A single-center trial at The Second Hospital of Anhui Medical University involved 136 elderly patients undergoing thoracoscopic esophageal cancer resection. Randomly assigned to maintain PaCO2 35-45 mmHg (group N) or 46-55 mmHg (group H). Primary outcome: postoperative delirium (POD) incidence 1-3 days post-surgery. Secondary endpoints included monitoring rSO2, cardiovascular parameters (MAP, HR), pH, OI, and respiratory parameters (VT, RR, Cdyn, PIP) at specific time points. Perioperative tests assessed CRP/ALB ratio (CAR) and systemic inflammatory index (SII). VAS scores were documented for three postoperative days. RESULTS: Postoperatively, group H showed significantly lower POD incidence than group N (7.4% vs. 19.1%, P = 0.043). Group H exhibited higher PaCO2 and rSO2 during surgery (P < 0.05). Patients in group H maintained better cardiovascular stability with higher blood pressure and lower heart rate on T2-4 (P < 0.05). Respiratory parameters were more stable in group H with lower TV, RR, and PIP, and higher Cdyn during OLV (P < 0.05). Group H had lower pH and OI at T2-4 (P < 0.05). CRP and CAR levels rose less in group H on the first day and one week later (P < 0.05). CONCLUSIONS: Maintaining PaCO2 at 46-55 mmHg reduces POD incidence, possibly by enhancing rSO2 levels and stabilizing intraoperative respiration/circulation.

Mechanisms of Triton X-100 reducing the Ag+-resistance of Enterococcus faecalis.

To investigate the mechanism of Triton X-100 (TX-100) reducing the Ag+-resistance of Enterococcus faecalis (E. faecalis), and evaluate the antibacterial effect of TX-100 + Ag+ against the induced Ag+-resistant E. faecalis (AREf). The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of AgNO3 against E. faecalis with/without TX-100 were determined to verify the enhanced antibacterial activity. Transmission electron microscopy (TEM) was used to observe the morphological changes of E. faecalis after treatment. The intra- and extracellular concentration of Ag+ in treated E. faecalis was evaluated using inductively coupled plasma mass spectrometer (ICP-MS). The changes in cell membrane potential and integrity of treated E. faecalis were also observed using the flow cytometer. Moreover, AREf was induced through continuous exposure to sub-MIC of Ag+ and the antibacterial effect of TX-100 + Ag+ on AREf was further evaluated. The addition of 0.04% TX-100 showed maximal enhanced antibacterial effect of Ag+ against E. faecalis. The TEM and ICP-MS results demonstrated that TX-100 could facilitate Ag+ to enter E. faecalis through changing the membrane structure and integrity. Flow cytometry further showed the effect of TX-100 on membrane potential and permeability of E. faecalis. In addition, the enhanced antibacterial effect of TX-100 + Ag+ was also confirmed on induced AREf. TX-100 can facilitate Ag+ to enter E. faecalis through disrupting the membrane structure and changing the membrane potential and permeability, thus reducing the Ag+-resistance of E. faecalis and enhancing the antibacterial effect against either normal E. faecalis or induced AREf.

Triton X-100 counteracts antibiotic resistance of Enterococcus faecalis: An in vitro study.

OBJECTIVES: The high prevalence of antibiotic-resistant bacteria poses a threat to the global public health. The appropriate use of adjuvants to restore the antimicrobial activity of antibiotics against resistant bacteria could be an effective strategy for combating antibiotic resistance. In this study, we investigated the counteraction of Triton X-100 (TX-100) and the mechanisms underlying the antibiotic resistance of Enterococcus faecalis (E. faecalis). METHODS: Standard, wild-type (WT), and induced antibiotic-resistant E. faecalis strains were used in this study. In vitro antibacterial experiments were conducted to evaluate the antimicrobial activities of gentamicin sulfate and ciprofloxacin hydrochloride in the presence and absence of 0.02 % TX-100 against both planktonic and biofilm bacteria. Transcriptomic and untargeted metabolomic analyses were performed to explore the molecular mechanisms of TX-100 as an antibiotic adjuvant. Additionally, membrane permeability, membrane potential, glycolysis-related enzyme activity, intracellular adenosine triphosphate (ATP), and expression levels of virulence genes were assessed. The biocompatibility of different drug combinations was also evaluated. RESULTS: A substantially low TX-100 concentration improved the antimicrobial effects of gentamicin sulfate or ciprofloxacin hydrochloride against antibiotic-resistant E. faecalis. Mechanistic studies demonstrated that TX-100 increased cell membrane permeability and dissipated membrane potential. Moreover, antibiotic resistance and pathogenicity of E. faecalis were attenuated by TX-100 via downregulation of the ABC transporter, phosphotransferase system (PTS), and ATP supply. CONCLUSIONS: TX-100 enhanced the antimicrobial activity of gentamicin sulfate and ciprofloxacin hydrochloride at a low concentration by improving antibiotic susceptibility and attenuating antibiotic resistance and pathogenicity of E. faecalis. CLINICAL SIGNIFICANCE: These findings provide a theoretical basis for developing new root canal disinfectants that can reduce antibiotic resistance.

Dental pulp regeneration strategies: A review of status quo and recent advances.

Microorganisms, physical factors such as temperature or mechanical injury, and chemical factors such as free monomers from composite resin are the main causes of dental pulp diseases. Current clinical treatment methods for pulp diseases include the root canal therapy, vital pulp therapy and regenerative endodontic therapy. Regenerative endodontic therapy serves the purpose of inducing the regeneration of new functional pulp tissues through autologous revascularization or pulp tissue engineering. This article first discusses the current clinical methods and reviews strategies as well as the research outcomes regarding the pulp regeneration. Then the in vivo models, the prospects and challenges for regenerative endodontic therapy were further discussed.

Targeting programmed cell death in inflammatory bowel disease through natural products: New insights from molecular mechanisms to targeted therapies.

Inflammatory bowel disease (IBD) is an autoimmune disorder primarily characterized by intestinal inflammation and recurrent ulceration, leading to a compromised intestinal barrier and inflammatory infiltration. This disorder's pathogenesis is mainly attributed to extensive damage or death of intestinal epithelial cells, along with abnormal activation or impaired death regulation of immune cells and the release of various inflammatory factors, which contribute to the inflammatory environment in the intestines. Thus, maintaining intestinal homeostasis hinges on balancing the survival and functionality of various cell types. Programmed cell death (PCD) pathways, including apoptosis, pyroptosis, autophagy, ferroptosis, necroptosis, and neutrophil extracellular traps, are integral in the pathogenesis of IBD by mediating the death of intestinal epithelial and immune cells. Natural products derived from plants, fruits, and vegetables have shown potential in regulating PCD, offering preventive and therapeutic avenues for IBD. This article reviews the role of natural products in IBD treatment by focusing on targeting PCD pathways, opening new avenues for clinical IBD management.

Risk of secondary autoimmune diseases with alemtuzumab treatment for multiple sclerosis: a systematic review and meta-analysis.

Background and purpose: The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a meta-analysis. Methods: PubMed, Web of Science, OVID, EMBASE, and Cochrane central register of controlled trials were searched. Information and data were screened and extracted by 2 researchers. The obtained data were analyzed using the R software meta package. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger's test. Results: The search retrieved a total of 3530 papers from the databases. After screening, a total of 37 studies were included in the meta-analysis. The analysis results indicate that the pooled incidence rate of overall secondary autoimmune events (SAEs) in the included studies was 0.2824 [0.2348, 0.3300] (I²=94%, p<0.01). The overall incidence of autoimmune thyroid events (ATE) was 0.2257 [0.1810, 0.2703] (I²=94%, p<0.01). Among them, the rate of serious autoimmune thyroid events (SATE) was 0.0541 [0.0396, 0.0687] (I²=0%, p=0.44). The incidence rates of different thyroid events were as follows: Graves' disease (GD), 0.2266 [0.1632, 0.2900] (I²=83%, p<0.01); Hashimoto thyroiditis (HT), 0.0844 [0.0000, 0.2262] (I²=81%, p=0.02); Hashimoto thyroiditis with hypothyroidism (HTwH), 0.0499 [0.0058, 0.0940] (I²=37%, p=0.21); fluctuating thyroid dysfunction (FTD), 0.0219 [0.0015, 0.0424] (I²=0%, p=0.40); transient thyroiditis (TT), 0.0178 [0.0062, 0.0295] (I²=0%, p=0.94). The overall incidence of hematological events was 0.0431 [0.0274, 0.0621] (I²=70%, p<0.01). The incidence rates from high to low were as follows: lymphopenia, 0.0367 [0.0000, 0.0776] (I²=81%, p=0.02); Idiopathic thrombocytopenic purpura (ITP), 0.0258 [0.0199, 0.0323] (I²=25%, p=0.15); Hemolytic anemia (HA), 0.0177 [0.0081, 0.0391] (I²=29%, p=0.23); pancytopenia, 0.0136 [0.0000, 0.0314] (I²=0%, p=0.67); Neutropenia, 0.0081 [0.0000, 0.0183] (I²=0%, p=0.42). After excluding thyroid and hematological diseases, the combined incidence of other related SAEs was 0.0061 [0.0014, 0.0109] (I²=50%, p=0.02). The incidence of each disease ranked from highest to lowest as: skin psoriasis (SP), 0.0430 [0.0000, 0.0929] (I²=0%, p=0.57); alopecia areata (AA), 0.0159 [0.0024, 0.0372] (I²=19%, p=0.29); vitiligo, 0.0134 [0.0044, 0.0223] (I²=0%, p=0.81); inflammatory atrichia (IA), 0.0103 [0.0000, 0.0232] (I²=0%, p=0.43); chronic urticaria (CU), 0.0107 [0.0000, 0.0233] (I²=0%, p=0.60); and nephropathy, 0.0051 [0.0000, 0.0263] (I²=62%, p=0.02). Conclusion: The occurrence of secondary autoimmune diseases in patients with MS treated with ALZ is noteworthy, particularly in the form of thyroid events and hematological events. Clinicians should monitor the overall condition of patients promptly for early management and avoid delayed diagnosis and treatment. Systematic review registration: inplasy.com/inplasy-2024-4-0048/, identifier INPLASY202440048.

Triton X-100 enhanced antibacterial effect of photodynamic therapy against Enterococcus faecalis infection: an in vitro study.

Photodynamic therapy (PDT) is an effective method for bacterial infection control in root canals of teeth with a broad-spectrum antibacterial activity. However, its application in root canal treatment is limited due to its inefficiency under hypoxic conditions and dentin staining. Triton X-100 (TX) shows great potential in enhancing the efficiency of antimicrobial agents through improving bacterial membrane permeability. The present study employed a combination of toluidine blue O (TB)-mediated PDT with TX to target the Enterococcus faecalis (E. faecalis), a bacterium with strong resistance to various antibacterial agents and mostly detected in infected root canals. PDT combined with TX showed enhanced antibacterial efficiency against both planktonic cells and biofilms of E. faecalis. At the same time, TX enhanced the antibacterial effect in dentinal tubules and reduced the incubation time. Mechanism studies revealed that TX improved reactive oxygen species (ROS) production through increasing the proportion of TB monomers. Additionally, increased membrane permeability and wettability were also observed. The findings demonstrated the PDT combined with TX could be used as a highly effective method for the root canal disinfection of teeth.

[The Efficacy and Safety of Venetoclax Combined with Azacitidine in the Treatment of Adult Patients with Acute Myeloid Leukemia Who Are Unfit for Intensive Chemotherapy].

OBJECTIVE: To observe the clinical efficacy and safety of venetoclax (VEN) combined with azacitidine (AZA) in the treatment of adult acute myeloid leukemia (AML) patients who are unfit for intensive chemotherapy. METHODS: The clinical data of 21 adult patients with unfit AML who were treated with VEN combined with AZA in the Second Hospital of Shanxi Medical University from January 2021 to May 2022 were collected, and the efficacy and safety were analyzed retrospectively. RESULTS: After one course of treatment with VEN and AZA, 16 out of 21 unfit AML patients reached complete remission (CR)/CR with incomplete hematologic recovery (CRi), 2 patients reached partial remission (PR), the overall response rate (ORR) was 85.7%. Among the 16 patients with CR/CRi, 13 achieved minimal residual disease (MRD) negativity. Among the 11 patients with adverse prognosis, 8 achieved CR/CRi. By the deadline of follow-up, the median overall suivival (OS) of the entire cohort was not reached, with 1-year OS rate of 61.7%. The main adverse events of VEN combined with AZA were myelosuppression, gastrointestinal reactions and infections. There were 13 cases of leukopenia, 7 cases of neutropenia, 7 cases of anemia, 4 cases of thrombocytopenia, and these hematologic adverse events were all grade 3-4. There were 11 cases with gastrointestinal reactions and 7 cases with infections. The above adverse events were controllable and tolerable. No tumor lysis syndrome or infection related death occurred. CONCLUSION: VEN combined with AZA can quickly achieve deep remission in adult patients with unfit AML, and it shows a good safety profile.

Mussel-inspired PDA@PEDOT nanocomposite hydrogel with excellent mechanical strength, self-adhesive, and self-healing properties for a flexible strain sensor.

Conductive hydrogel sensors have attracted attention for use in human motion monitoring detection, but integrating excellent biocompatibility, mechanical, self-adhesive, and self-healing properties, and high sensitivity into a hydrogel remains a challenge. In this work, a novel multifunctional conductive particle was designed and added to a polyacrylamide (PAM) matrix to prepare the hydrogel. It is worth noting that with the addition of polydopamine@poly(3,4-ethylenedioxythiophene) (PDA@PEDOT), the PAM/PDA@PEDOT hydrogel (PAPP hydrogel) showed excellent mechanical properties and high adhesion strength on different substrate surfaces. Meanwhile, the PAPP hydrogel shows outstanding self-healing properties, the mechanical properties of PAPP hydrogel broken from the middle recovered 92% tensile strength and 95% elongation at break after 12 h, respectively. Furthermore, assembled as strain wireless sensors, the PAPP sensor displays high sensitivity, where the gauge factor (GF) is 2.82, which can be used to accurately detect human facial micro-expressions and movements. Overall, the PAPP hydrogel with excellent mechanical, self-adhesive, and self-healing properties, and high sensitivity, demonstrated promise for use in wearable devices and bionic skins.

Metformin switches cell death modes to soothe the apical periodontitis via ZBP1.

Apical periodontitis (AP) is a disease caused by pathogenic microorganisms and featured with the degradation of periapical hard tissue. Our recent research showed the crucial role of Z-DNA binding protein 1 (ZBP1)-mediated necroptosis and apoptosis in the pathogenesis of AP. However, the specific regulatory mechanisms of ZBP1 in AP are not fully elucidated. It was found that metformin has a regulatory role in cell necroptosis and apoptosis. But whether and how metformin regulates necroptosis and apoptosis through the ZBP1 in the context of AP remains unknown. This study provided evidence that lipopolysaccharide (LPS) promotes the synthesis of left-handed Z-nucleic acids (Z-NA), which in turn activates ZBP1. Knockout of Zbp1 by CRISPR/Cas9 technology significantly reduced LPS-induced necroptosis and apoptosis in vitro. By using Zbp1-knockout mice, periapical bone destruction was alleviated. Moreover, type I interferon induced the expression of interferon-stimulated genes (ISGs), which serve as a major source of Z-NA. In addition, the RNA-editing enzyme Adenosine Deaminase RNA specific 1 (ADAR1) prevented the accumulation of endogenous Z-NA. Meanwhile, metformin suppressed the ZBP1-mediated necroptosis by inhibiting the expression of ZBP1 and the accumulation of ISGs. Metformin also promoted mitochondrial apoptosis, which is critical for the elimination of intracellular bacterial infection. The enhanced apoptosis further promoted the healing of infected apical bone tissues. In summary, these results demonstrated that the recognition of Z-NA by ZBP1 plays an important role in AP pathogenesis. Metformin suppressed ZBP1-mediated necroptosis and promoted apoptosis, thereby contributing to the soothing of inflammation and bone healing in AP.

Expert consensus on irrigation and intracanal medication in root canal therapy.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes. Additionally, ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified. Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes. Indeed, clinicians have been aware of these concerns for years. Based on the current evidence of studies, this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions. The evolution of different kinetic irrigation methods, their effects, limitations, the paradigm shift, current indications, and effective operational procedures regarding intracanal medication are also discussed. This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication, thus facilitating a better understanding of infection control, standardizing clinical practice, and ultimately improving the success of endodontic therapy.

Clinical efficacy of acupuncture in treating postoperative gastrointestinal dysfunction of colorectal cancer, a systematic review and Meta analysis. / é’ˆåˆºæ²»ç–—ç»“ç›´è‚ ç™Œæœ¯åŽèƒƒè‚ åŠŸèƒ½éšœç¢ç–—æ•ˆçš„ 系统评价和Meta分析.

OBJECTIVES: To evaluate the efficacy of acupuncture in the treatment of postoperative gastrointestinal dysfunction(POGD) of colorectal cancer. METHODS: Randomized controlled trials of acupuncture in the treatment of POGD were retrieved from 7 databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP Chinese Journal Service Platform, WanFang Data Knowledge Service Platform, and China Biology Medicine disc. The search period ranged from the inception of the databases to November 10th, 2022. The quality of the included literature was assessed using the Cochrane bias risk assessment tool and the modified Jadad scale. Meta analysis was conducted using RevMan 5.4. Regression analysis and bias risk analysis were performed using Stata 16.0. Trial sequential analysis was conducted using TSA 0.9 software. RESULTS: A total of 27 randomized controlled trials involving 2 629 patients were included. Intervention measures included manual acupuncture, electroacupuncture, transcutaneous acupoint electrical stimulation, warm acupuncture, and thumb-tack needle. The results showed that acupuncture treatment significantly reduced time to tolerance of liquid diet after surgery (MD=-13.70, 95% CI=ï¼»-17.94, -9.46ï¼½, P<0.000 01), time to first defecation (MD=-18.20, 95% CI=ï¼»-22.62, -13.78ï¼½, P<0.000 01), time to first flatus (MD=-16.31, 95% CI=ï¼»-20.32, -12.31ï¼½, P<0.000 01), time to bowel sounds recovery (MD=-11.91, 95% CI=ï¼»-14.01, -9.81ï¼½, P<0.000 01), and length of hospital stay (MD=-1.49, 95% CI=ï¼»-2.27, -0.70ï¼½, P=0.000 2). Regression analysis indicated that cancer type, study quality and number of acupuncture were the main sources of heterogeneity. Bias analysis suggested potential publication bias risks. Trial sequential analysis indicated that the required number of cases had been met and the conclusion was reliable. CONCLUSIONS: Acupuncture is an effective intervention for promoting gastrointestinal recovery in patients undergoing colorectal cancer surgery. Further large-sample and well-designed clinical trials are still needed to compare different acupuncture techniques.

CT whole lung radiomic nomogram: a potential biomarker for lung function evaluation and identification of COPD.

BACKGROUND: Computed tomography (CT) plays a great role in characterizing and quantifying changes in lung structure and function of chronic obstructive pulmonary disease (COPD). This study aimed to explore the performance of CT-based whole lung radiomic in discriminating COPD patients and non-COPD patients. METHODS: This retrospective study was performed on 2785 patients who underwent pulmonary function examination in 5 hospitals and were divided into non-COPD group and COPD group. The radiomic features of the whole lung volume were extracted. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied for feature selection and radiomic signature construction. A radiomic nomogram was established by combining the radiomic score and clinical factors. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the predictive performance of the radiomic nomogram in the training, internal validation, and independent external validation cohorts. RESULTS: Eighteen radiomic features were collected from the whole lung volume to construct a radiomic model. The area under the curve (AUC) of the radiomic model in the training, internal, and independent external validation cohorts were 0.888 [95% confidence interval (CI) 0.869-0.906], 0.874 (95%CI 0.844-0.904) and 0.846 (95%CI 0.822-0.870), respectively. All were higher than the clinical model (AUC were 0.732, 0.714, and 0.777, respectively, P < 0.001). DCA demonstrated that the nomogram constructed by combining radiomic score, age, sex, height, and smoking status was superior to the clinical factor model. CONCLUSIONS: The intuitive nomogram constructed by CT-based whole-lung radiomic has shown good performance and high accuracy in identifying COPD in this multicenter study.