In situ implantable DNA hydrogel for diagnosis and therapy of postoperative rehemorrhage following intracerebral hemorrhage surgery.

Postoperative rehemorrhage following intracerebral hemorrhage surgery is intricately associated with a high mortality rate, yet there is now no effective clinical treatment. In this study, we developed a hemoglobin (Hb)-responsive in situ implantable DNA hydrogel comprising Hb aptamers cross-linked with two complementary chains and encapsulating deferoxamine mesylate (DFO). Functionally, the hydrogel generates signals upon postoperative rehemorrhage by capturing Hb, demonstrating a distinctive "self-diagnosis" capability. In addition, the ongoing capture of Hb mediates the gradual disintegration of the hydrogel, enabling the on-demand release of DFO without compromising physiological iron-dependent functions. This process achieves self-treatment by inhibiting the ferroptosis of neurocytes. In a collagenase and autologous blood injection model-induced mimic postoperative rehemorrhage model, the hydrogel exhibited a 5.58-fold increase in iron absorption efficiency, reducing hematoma size significantly (from 8.674 to 4.768 cubic millimeters). This innovative Hb-responsive DNA hydrogel not only offers a therapeutic intervention for postoperative rehemorrhage but also provides self-diagnosis feedback, holding notable promise for enhancing clinical outcomes.

Tumor-exosomal miR-205-5p as a diagnostic biomarker for colorectal cancer.

BACKGROUND: Tumor-derived exosomal miRNAs play crucial roles in cancer diagnosis. Current studies aim to identify exosomal miRNAs associated with colorectal cancer (CRC) that are noninvasive, sensitive, and specific. PATIENTS AND METHODS: Exosomes were extracted from CRC patients and healthy donors via ultracentrifugation, followed by verification via transmission electron microscopy (TEM), qNano, and Western blot analysis. The differential expression levels and clinical characteristics of miR-205-5p were analyzed in CRC via data from The Cancer Genome Atlas (TCGA). Real-time quantitative PCR was used to assess the expression levels of exosomal miRNAs in 157 primary CRC patients, 20 patients with benign diseases, and 135 healthy donors. Predictions regarding target genes were made to guide further exploration of the disease's etiopathogenesis through bioinformatics. RESULTS: Compared with that in healthy donors, the expression of miR-205-5p in colorectal cancer (CRC) patients was significantly lower, as determined through analysis of the TCGA database. We conducted a prediction and analysis of the functional enrichment of downstream target genes regulated by miR-205-5p. A lower level of exosomal miR-205-5p in the serum of CRC patients than in that of healthy controls (p < 0.0001) and patients with benign disease (p < 0.0001) was observed. Furthermore, the expression levels of exosomal miR-205-5p were significantly lower in early-stage CRC patients than in the comparison groups (p<0.001 and p < 0.0001). Notably, the expression levels of exosomal miR-205-5p significantly increased postoperatively (p = 0.0053). CONCLUSIONS: The present study demonstrated that serum exosomal miR-205-5p may be a diagnostic biomarker for CRC.

Acid-Resistant Nano-antioxidants Based on Epigallocatechin Gallate Alleviate Acute Intestinal and Kidney Inflammation.

Epigallocatechin gallate (EGCG)-based nanosystems have garnered significant attention for their ability to alleviate inflammation due to their excellent anti-inflammatory properties and enhanced drug delivery capabilities. However, the degradation of EGCG in strongly acidic environments poses a challenge for potential administration, particularly in oral formulations, where gastric resistance is essential. In this study, we develop a "disintegration and reorganization" strategy to create acid-resistant antioxidant nanoparticles (EGA NPs) based on EGCG and 5-aminosalicylic acid (5-ASA) for mitigating inflammation in colitis and acute kidney injury. At acidic pH, the ester bond in EGCG breaks down, producing two building blocks. These, together with 5-ASA and formaldehyde, form oligomers through a combination of phenol-aldehyde condensation and the Mannich reaction. The resulting oligomers self-assemble into EGA NPs, which exhibit significant stability under both acidic and neutral pH conditions. This stability makes them suitable for oral administration, allowing them to withstand harsh gastric conditions, as well as for intravenous injection. Importantly, these oligomers retain the antioxidant and anti-inflammatory properties of EGCG, effectively scavenging reactive oxygen species and reducing intracellular oxidative stress. Additionally, EGA shows potential as a drug carrier, efficiently loading the anti-inflammatory agent curcumin (Cur) to form Cur@EGA NPs. In vivo studies demonstrate the efficacy of Cur@EGA and EGA in alleviating acute colitis and kidney injury following oral and intravenous administration, respectively. These nanoparticulate formulations exhibit superior inflammation reduction compared to free Cur in vivo. Overall, our findings introduce a novel acid-resistant nanoplatform based on EGCG for the treatment of acute inflammation.

Circular RNA IGF1R Promotes Cardiac Repair via Activating ß-Catenin Signaling by Interacting with DDX5 in Mice after Ischemic Insults.

The potential of circular RNAs (circRNAs) as biomarkers and therapeutic targets is becoming increasingly evident, yet their roles in cardiac regeneration and myocardial renewal remain largely unexplored. Here, we investigated the function of circIGF1R and related mechanisms in cardiac regeneration. Through analysis of circRNA sequencing data from neonatal and adult cardiomyocytes, circRNAs associated with regeneration were identified. Our data showed that circIGF1R expression was high in neonatal hearts, decreased with postnatal maturation, and up-regulated after cardiac injury. The elevation was validated in patients diagnosed with acute myocardial infarction (MI) within 1 week. In human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and myocardial tissue from mice after apical resection and MI, we observed that circIGF1R overexpression enhanced cardiomyocyte proliferation, reduced apoptosis, and mitigated cardiac dysfunction and fibrosis, while circIGF1R knockdown impeded endogenous cardiac renewal. Mechanistically, we identified circIGF1R binding proteins through circRNA precipitation followed by mass spectrometry. RNA pull-down Western blot and RNA immunoprecipitation demonstrated that circIGF1R directly interacted with DDX5 and augmented its protein level by suppressing ubiquitin-dependent degradation. This subsequently triggered the ß-catenin signaling pathway, leading to the transcriptional activation of cyclin D1 and c-Myc. The roles of circIGF1R and DDX5 in cardiac regeneration were further substantiated through site-directed mutagenesis and rescue experiments. In conclusion, our study highlights the pivotal role of circIGF1R in facilitating heart regeneration and repair after ischemic insults. The circIGF1R/DDX5/ß-catenin axis emerges as a novel therapeutic target for enhancing myocardial repair after MI, offering promising avenues for the development of regenerative therapies.

Biomaterials based on advanced oxidation processes in tooth whitening: fundamentals, progress, and models.

The increasing desire for aesthetically pleasing teeth has resulted in the widespread use of tooth whitening treatments. Clinical tooth whitening products currently rely on hydrogen peroxide formulations to degrade dental pigments through oxidative processes. However, they usually cause side effects such as tooth sensitivity and gingival irritation due to the use of high concentrations of hydrogen peroxide or long-time contact. In recent years, various novel materials and reaction patterns have been developed to tackle the issues related to H2O2-based tooth whitening. These can be broadly classified as advanced oxidation processes (AOPs). AOPs generate free radicals that have potent oxidizing properties, which can thereby increase the oxidation power and/or reduce the exposure time and can probably minimize the side effects of tooth bleaching. While there have been several reviews on clinical tooth whitening and the application of novel nanomaterials, a review based on the concept of AOPs in tooth bleaching application has not yet been conducted. This review describes the common types and mechanisms of AOPs, summarizes the latest research progress of new tooth bleaching materials based on AOPs, and proposes a model for tooth bleaching and a rate control step at the molecular level. The paper also reviews the shortcomings and suggests future development directions.

Temporal trends of ischemic stroke attributable to high fasting plasma glucose in China from the global burden of disease study 2019.

Background: Currently ischemic stroke poses a serious disease burden globally, and high fasting plasma glucose is one of the important risk factors. The aim of this study was to investigate the disease burden of ischemic stroke due to fasting glucose during 1990-2019 in China, to estimate the effect of age, period, and cohort on the trend of ischemic stroke disease burden, and to predict the disease burden of ischemic stroke in 2020-2030. Methods: Ischemic stroke burden data were obtained by screening from the Global Burden of Disease Study 2019 (GBD 2019) database for high-risk populations in China. Annual average percentage change (AAPC) was calculated using the Joinpoint regression model to assess the trend of ischemic stroke burden between 1990 and 2019. Age-period-cohort models were introduced to estimate the independent effects of age, period, and cohort on ischemic stroke burden, and to predict the ischemic stroke burden in 2020-2030 based on Bayesian age-period-cohort models. Results: From 1990 to 2019, the number of ischemic stroke deaths due to high fasting plasma glucose in China continued to increase with an AAPC of 3.61. Trends in age-standardized incidence rates did not show statistical significance. In the age-period-cohort analysis, the age effect of ischemic stroke burden showed a continuously increasing trend over the study period. The period effect showed an overall favorable trend over the study period. The overall and cohort effects for males showed an overall increasing trend, whereas the cohort effect for females showed a decreasing trend after a decreasing trend for the 1945 birth cohort. Conclusions: This study found that ischemic stroke due to high fasting plasma glucose in China has generally fluctuated between 1990 and 2019, with a decreasing trend in recent years, and projections also suggest that it will continue to show a decreasing trend in the future. Age and period of birth were the main elements influencing the burden of disease, especially among the elderly and men. Policies should be used to promote the prevention of known risk factors and to strengthen health management for key populations.

Causal associations of BAFF-R on IgD+ CD24- B cell immune cell trait with hepatocellular carcinoma and the mediating role of phenylacetylglutamate levels: a Mendelian randomization study.

We conducted a bi-directional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between immune cell traits and hepatocellular carcinoma (HCC) and identified the mediating factor of metabolites. The exposure factors were immune cell traits, the mediators were metabolites, and the outcome variable was HCC. Inverse-variance weighted method (IVW) was the main method. Weighted median, MR-Egger regression, weighted mode, simple mode, and MR pleiotropy residual sum and outlier (MRPRESSO) methods were used as complementary methods. The results were tested by using the Bayesian weighted Mendelian randomization (BWMR) approach in our MR study. Subsequently, the potential mediating effect was investigated by conducting a two-step mediation analysis. We identified 26 traits with suggestive correlations between immune cell traits and HCC, with 4 immune cell traits among them having causal correlations with HCC. There were no causal correlations between HCC and immune cell traits in the reverse MR analysis. In the mediation analysis, we found a positive causal association between B cell-activating factor receptors (BAFF-R) on IgD+ CD24- B cell and HCC [IVW: odd ratio (OR), 0.845; 95% CI, 0.759-0.942; p = 0.002]. Phenylacetylglutamate (PAG) levels mediated 7.353% of the causal pathway from BAFF-R on IgD+ CD24- B cell and HCC. In conclusion, BAFF-R on IgD+ CD24- B cell lowers risk of HCC, with PAG levels playing a mediating role.

PRIORITI: Phase 4 study of triptorelin or active surveillance in high-risk prostate cancer.

AIM: To evaluate the efficacy and safety of triptorelin after radical prostatectomy (RP) in patients with negative lymph nodes. METHODS: PRIORITI (NCT01753297) was a prospective, open-label, randomized, controlled, phase 4 study conducted in China and Russia. Patients with high-risk (Gleason score ≥ 8 and/or pre-RP prostate-specific antigen [PSA] ≥ 20 ng/mL and/or primary tumor stage 3a) prostate adenocarcinoma without evidence of lymph node or distant metastases were randomized to receive triptorelin 11.25 mg at baseline (≤ 8 weeks after RP) and at 3 and 6 months, or active surveillance. The primary endpoint was biochemical relapse-free survival (BRFS), defined as the time from randomization to biochemical relapse (BR; increased PSA > 0.2 ng/mL). Patients were monitored every 3 months for at least 36 months; the study ended when 61 BRs were observed. RESULTS: The intention-to-treat population comprised 226 patients (mean [standard deviation] age, 65.3 [6.4] years), of whom 109 and 117 were randomized to triptorelin or surveillance, respectively. The median BRFS was not reached. The 25th percentile time to BRFS (95% confidence interval) was 39.1 (29.9-not estimated) months with triptorelin and 30.0 (18.6-42.1) months with surveillance (p = 0.16). There was evidence of a lower risk of BR with triptorelin versus surveillance but this was not statistically significant at the 5% level (p = 0.10). Chemical castration was maintained at month 9 in 93.9% of patients who had received triptorelin. Overall, triptorelin was well tolerated and had an acceptable safety profile. CONCLUSION: BRFS was observed to be longer with triptorelin than surveillance, but the difference was not statistically significant.

LILRB4 regulates multiple myeloma development through STAT3-PFKFB1 pathway.

Although multiple myeloma (MM) responds well to immunotherapeutic treatment, certain portions of MM are still unresponsive or relapse after immunotherapy. Other immune molecules are needed for the immunotherapy of MM. Here, we revealed that leukocyte immunoglobulin-like receptor B4 (LILRB4) was highly expressed in multiple myeloma cell lines and patient samples and that the expression of LILRB4 was adversely correlated with the overall survival of MM patients. Knockdown of LILRB4 efficiently delayed the growth of MM cells both in vitro and in vivo. Mechanistically, IKZF1 transactivated LILRB4 expression to trigger the downstream of STAT3-PFKFB1 pathways to support MM cell proliferation. Blockade of LILRB4 signaling by blocking antibodies can effectively inhibit MM progression. Our data show that targeting LILRB4 is potentially an additional therapeutic strategy for the immunotherapeutic treatment of MM.

Cu Single-Atom Nanozyme-Mediated Electrochemiluminescence Biosensor for Highly Sensitive Detection of MicroRNA-622.

MicroRNA (miRNA) detection is a critical aspect of disease diagnosis, and recent studies indicate that miRNA-622 could be a potential target for lung cancer. Herein, Cu single atoms were anchored on graphitic carbon nitride (Cu SAs@CN) as a coreaction accelerator applied in luminol-H2O2 system, thereby establishing an efficient and sensitive electrochemiluminescence (ECL) biosensor for miRNA-622 detection. Cu SAs@CN was explored to possess excellent enzyme-like activities that promote the generation of abundant reactive oxygen species, which amplified ECL emission. Meanwhile, in order to improve the accuracy and sensitivity for miRNA-622 detection, the highly specific trans-cleavage ability of CRISPR/Cas12a was combined with a catalytic hairpin assembly strategy. Therefore, an ECL biosensor for miRNA-622 detection was systematically constructed as a proof of concept, achieving an ultralow limit of detection of 1.09 fM, and the feasibility was demonstrated in human serum samples. The findings of this research provide a promising strategy to enhance the ECL response using versatile single-atom catalysts, thus advancing the development of ECL biosensing applications.

Ultrahigh proton conductivity of four ionic hydrogen-bonded organic frameworks based on functionalized terephthalates.

Recently, the utilization of hydrogen-bonded organic frameworks (HOFs) with high crystallinity and inherent well-defined H-bonding networks in the field of proton conduction has received increasing attention, but obtaining HOFs with excellent water stability and prominent proton conductivity (σ) remains challenging. Herein, by employing functionalized terephthalic acids, 2,5-dihydroxyterephthalic acid, 2-hydroxyterephthalic acid, 2-nitro terephthalic acid, and terephthalic acid, respectively, four highly water-stable ionic HOFs (iHOFs), [(C8H5O6)(Me2NH2)]∙2H2O (iHOF 1), [(C8H5O5)(Me2NH2)] (iHOF 2), [(C8H4NO6)(Me2NH2)] (iHOF 3) and [(C8H5O4)(Me2NH2)] (iHOF 4) were efficiently prepared by a straightforward synthesis approach in DMF and H2O solutions. The alternating-current (AC) impedance testing in humid conditions revealed that all four iHOFs were temperature- and humidity-dependent σ, with the greatest value reaching 10-2 S·cm-1. As expected, the high density of free carboxylic acid groups, crystallization water, and protonated [Me2NH2]+ units offer adequate protons and hydrophilic environments for effective proton transport. Furthermore, the σ values of these iHOFs with different functional groups were compared. It was discovered that it dropped in the following order under 100 °C and 98 % relative humidity (RH): σ iHOF 1 (1.72 × 10-2 S·cm-1) > σ iHOF 2 (4.03 × 10-3 S·cm-1) > σ iHOF 3 (1.46 × 10-3 S·cm-1) > σ iHOF 4 (4.86 × 10-4 S·cm-1). Finally, we investigated the causes of the above differences and the proton transport mechanism inside the framework using crystal structure data, water contact angle tests, and activation energy values. This study provides new motivation to develop highly proton-conductive materials.

Predicting the Risk of Postoperative Delirium in Elderly Patients Undergoing Hip Arthroplasty: Development and Assessment of a Novel Nomogram.

OBJECTIVE: To construct and internally validate a nomogram that predicts the likelihood of postoperative delirium in a cohort of elderly individuals undergoing hip arthroplasty. METHODS: Data for a total of 681 elderly patients underwent hip arthroplasty were retrospectively collected and divided into a model (n = 477) and a validation cohort (n = 204) according to the principle of 7:3 distribution temporally. The assessment of postoperative cognitive function was conducted through the utilization of The Confusion Assessment Method (CAM). The nomogram model for postoperative cognitive impairments was established by a combination of Lasso regression and logistic regression. The receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were used to evaluate the performance. RESULTS: The nomogram utilized various predictors, including age, body mass index (BMI), education, preoperative Barthel Index, preoperative hemoglobin level, history of diabetes, and history of cerebrovascular disease, to forecast the likelihood of postoperative delirium in patients. The area under the ROC curves (AUC) for the nomogram, incorporating the aforementioned predictors, was 0.836 (95% CI: 0.797-0.875) for the training set and 0.817 (95% CI: 0.755-0.880) for the validation set. The calibration curves for both sets indicated a good agreement between the nomogram's predictions and the actual probabilities. CONCLUSION: The use of this novel nomogram can help clinicians predict the likelihood of delirium after hip arthroplasty in elderly patients and help prevent and manage it in advance.

Efficacy and Safety of Chidamide in Combination with PD-1 Inhibitor and Radiotherapy for HER2-Negative Advanced Breast Cancer: Study Protocol of a Single Arm Prospective Study.

Purpose: As one of the most important breakthroughs in cancer therapy, immune checkpoint inhibitors have greatly prolonged survival of patients with breast cancer. However, their application and efficacy are limited, especially for advanced HER2-negative breast cancer. It has been reported that epigenetic modulation of the histone deacetylase (HDAC) inhibitor chidamide, as well as immune microenvironment modulation of radiotherapy are potentially synergistic with immunotherapy. Thus, the combination of chidamide, radiotherapy and immunotherapy is expected to improve prognosis of patients with advanced HER2-negative breast cancer. Patients and Methods: This is a single-arm, open, prospective clinical trial investigating the efficacy and safety of the combination of HDAC inhibitor chidamide, anti-PD-1 antibody sintilimab, and the novel immuno-radiotherapy, which aims to enhance efficacy of immunotherapy, in subsequent lines of therapy of HER2-negative breast cancer. Our study will include 35 patients with advanced breast cancer that has failed endocrine therapy and first-line chemotherapy. Participants will receive 30 mg of chidamide twice a week, 200 mg of sintilimab once every 3 weeks, combined with immuno-radiotherapy. Radiotherapy will be centrally 8 Gy for at least one lesion, and at least 1 Gy for the other lesions. We will complete three fractions of radiotherapy in one cycle. The primary endpoint is progression-free survival, and secondary endpoints are objective response rate, disease control rate and safety. Moreover, biomarkers including cytokines and lymphocyte subgroups will be explored. Conclusion: As a single-arm clinical trial, the analysis of the influence of each single treatment is limited. Besides, our study is an open study, which involves neither randomization nor blinding. In spite of the abovementioned limitations, this prospective clinical trial will give an insight into subsequent lines of therapy of HER2-negative advanced breast cancer, prolong the survival or achieve long remission for these participants, and identify potential responders.

Elucidating the role of angiogenesis-related genes in colorectal cancer: a multi-omics analysis.

Background: Angiogenesis plays a pivotal role in colorectal cancer (CRC), yet its underlying mechanisms demand further exploration. This study aimed to elucidate the significance of angiogenesis-related genes (ARGs) in CRC through comprehensive multi-omics analysis. Methods: CRC patients were categorized according to ARGs expression to form angiogenesis-related clusters (ARCs). We investigated the correlation between ARCs and patient survival, clinical features, consensus molecular subtypes (CMS), cancer stem cell (CSC) index, tumor microenvironment (TME), gene mutations, and response to immunotherapy. Utilizing three machine learning algorithms (LASSO, Xgboost, and Decision Tree), we screen key ARGs associated with ARCs, further validated in independent cohorts. A prognostic signature based on key ARGs was developed and analyzed at the scRNA-seq level. Validation of gene expression in external cohorts, clinical tissues, and blood samples was conducted via RT-PCR assay. Results: Two distinct ARC subtypes were identified and were significantly associated with patient survival, clinical features, CMS, CSC index, and TME, but not with gene mutations. Four genes (S100A4, COL3A1, TIMP1, and APP) were identified as key ARCs, capable of distinguishing ARC subtypes. The prognostic signature based on these genes effectively stratified patients into high- or low-risk categories. scRNA-seq analysis showed that these genes were predominantly expressed in immune cells rather than in cancer cells. Validation in two external cohorts and through clinical samples confirmed significant expression differences between CRC and controls. Conclusion: This study identified two ARG subtypes in CRC and highlighted four key genes associated with these subtypes, offering new insights into personalized CRC treatment strategies.

TRIM50 inhibits glycolysis and the malignant progression of gastric cancer by ubiquitinating PGK1.

Ubiquitination plays a pivotal regulatory role in tumor progression. Among the components of the ubiquitin-proteasome system (UPS), ubiquitin-protein ligase E3 has emerged as a key molecule. Nevertheless, the biological functions of E3 ubiquitin ligases and their potential mechanisms orchestrating glycolysis in gastric cancer (GC) remain to be elucidated. In this study, we conducted a comprehensive transcriptomic analysis to identify the core E3 ubiquitin ligases in GC, followed by extensive validation of the expression patterns and clinical significance of Tripartite motif-containing 50 (TRIM50) both in vitro and in vivo. Remarkably, we found that TRIM50 was downregulated in GC tissues, associated with malignant progression and poor patient survival. Functionally, overexpression of TRIM50 suppressed GC cell proliferation and indirectly mitigated the invasion and migration of GC cells by inhibiting the M2 polarization of tumor-associated macrophages (TAMs). Mechanistically, TRIM50 inhibited the glycolytic pathway by ubiquitinating Phosphoglycerate Kinase 1 (PGK1), thereby directly suppressing GC cell proliferation. Simultaneously, the reduction in lactate led to diminished M2 polarization of TAMs, indirectly inhibiting the invasion and migration of GC cells. Notably, the downregulation of TRIM50 in GC was mediated by the METTL3/YTHDF2 axis in an m6A-dependent manner. In our study, we definitively identified TRIM50 as a tumor suppressor gene (TSG) that effectively inhibits glycolysis and the malignant progression of GC by ubiquitinating PGK1, thus offering novel insights and promising targets for the diagnosis and treatment of GC.

ETS1-mediated Regulation of SOAT1 Enhances the Malignant Phenotype of Oral Squamous Cell Carcinoma and Induces Tumor-associated Macrophages M2-like Polarization.

Oral squamous cell carcinoma (OSCC) is an aggressive cancer that poses a substantial threat to human life and quality of life globally. Lipid metabolism reprogramming significantly influences tumor development, affecting not only tumor cells but also tumor-associated macrophages (TAMs) infiltration. SOAT1, a critical enzyme in lipid metabolism, holds high prognostic value in various cancers. This study revealed that SOAT1 is highly expressed in OSCC tissues and positively correlated with M2 TAMs infiltration. Increased SOAT1 expression enhanced the capabilities of cell proliferation, tumor sphere formation, migration, and invasion in OSCC cells, upregulated the SREBP1-regulated adipogenic pathway, activated the PI3K/AKT/mTOR pathway and promoted M2-like polarization of TAMs, thereby contributing to OSCC growth both in vitro and in vivo. Additionally, we explored the upstream transcription factors that regulate SOAT1 and discovered that ETS1 positively regulates SOAT1 expression levels. Knockdown of ETS1 effectively inhibited the malignant phenotype of OSCC cells, whereas restoring SOAT1 expression significantly mitigated this suppression. Based on these findings, we suggest that SOAT1 is regulated by ETS1 and plays a pivotal role in the development of OSCC by facilitating lipid metabolism and M2-like polarization of TAMs. We propose that SOAT1 is a promising target for OSCC therapy with tremendous potential.

Molecular epidemiology and genomic features of Bordetella parapertussis in Shanghai, China, 2017-2022.

Background: Pertussis is a highly contagious respiratory illness mainly caused by Bordetella pertussis (BP). Bordetella parapertussis (BPP) can induce symptoms compatible with pertussis, but has been underdiagnosed and underreported. The current pertussis vaccines offer low protection against BPP. Herein, we aim to reveal the epidemiology and genomic evolution of BPP in Shanghai, China. Methods: Children diagnosed with BPP infection from January 2017 to December 2022 in Shanghai, China were enrolled. We performed antimicrobial susceptibility testing (AST), multiple locus variable-number tandem repeat analysis (MLVA), and whole genome sequencing (WGS) analysis. A total of 260 international BPP genomes were chosen for comparison to investigate the genomic diversity and phylogenetic characteristics of Chinese strains within a global context. Results: Sixty patients were diagnosed with BPP infection by culture, with the positive ratio of 3.5‰ (60/17337) for BPP in nasopharyngeal swap samples. The average age of patients was 4.5 ± 0.3 years. BPPs contained four MLVA types including MT6 (65.0%), MT4 (26.7%), untype-1 (6.7%) and MT5 (1.7%), and none of strains showed resistance to macrolides. All strains carried virulence genotype of ptxP37/ptxA13/ptxB3/ptxC3/ptxD3/ptxE3/fim2-2/fim3-10. MT4 and MT5 strains carried prn54, whereas MT6 and untype-1 BPPs expressed prn101. We identified two outbreaks after 2020 caused by MT4 and MT6 strains, each corresponding to distinct WGS-based phylogenetic lineages. The MT4-lineage is estimated to have originated around 1991 and has since spread globally, being introduced to China between 2005 and 2010. In contrast, the MT6-lineage was exclusively identified in China and is inferred to have originated around 2002. Conclusion: We revealed the genomic diversity of BPPs circulating in Shanghai, China, and reported the outbreaks of MT6 and MT4 BPPs after 2020. This is the first report on the emergence and regional outbreak of MT6 BPPs in the world, indicating that continuous surveillance on BPPs are thus required.

Traumatic brain injury in elderly population: A global systematic review and meta-analysis of in-hospital mortality and risk factors among 2.22 million individuals.

BACKGROUND: Traumatic brain injury (TBI) among elderly individuals poses a significant global health concern due to the increasing ageing population. METHODS: We searched PubMed, Cochrane Library, and Embase from database inception to Feb 1, 2024. Studies performed in inpatient settings reporting in-hospital mortality of elderly people (≥60 years) with TBI and/or identifying risk factors predictive of such outcomes, were included. Data were extracted from published reports, in-hospital mortality as our main outcome was synthesized in the form of rates, and risk factors predicting in-hospital mortality was synthesized in the form of odds ratios. Subgroup analyses, meta-regression and dose-response meta-analysis were used in our analyses. FINDINGS: We included 105 studies covering 2217,964 patients from 30 countries/regions. The overall in-hospital mortality of elderly patients with TBI was 16 % (95 % CI 15 %-17 %) from 70 studies. In-hospital mortality was 5 % (95 % CI, 3 %-7 %), 18 % (95 % CI, 12 %-24 %), 65 % (95 % CI, 59 %-70 %) for mild, moderate and severe subgroups from 10, 7, and 23 studies, respectively. A decrease in in-hospital mortality over years was observed in overall (1981-2022) and in severe (1986-2022) elderly patients with TBI. Older age 1.69 (95 % CI, 1.58-1.82, P < 0.001), male gender 1.34 (95 % CI, 1.25-1.42, P < 0.001), clinical conditions including traffic-related cause of injury 1.22 (95 % CI, 1.02-1.45, P = 0.029), GCS moderate (GCS 9-12 compared to GCS 13-15) 4.33 (95 % CI, 3.13-5.99, P < 0.001), GCS severe (GCS 3-8 compared to GCS 13-15) 23.09 (95 % CI, 13.80-38.63, P < 0.001), abnormal pupillary light reflex 3.22 (95 % CI, 2.09-4.96, P < 0.001), hypotension after injury 2.88 (95 % CI, 1.06-7.81, P = 0.038), polytrauma 2.31 (95 % CI, 2.03-2.62, P < 0.001), surgical intervention 2.21 (95 % CI, 1.22-4.01, P = 0.009), pre-injury health conditions including pre-injury comorbidity 1.52 (95 % CI, 1.24-1.86, P = 0.0020), and pre-injury anti-thrombotic therapy 1.51 (95 % CI, 1.23-1.84, P < 0.001) were related to higher in-hospital mortality in elderly patients with TBI. Subgroup analyses according to multiple types of anti-thrombotic drugs with at least two included studies showed that anticoagulant therapy 1.70 (95 % CI, 1.04-2.76, P = 0.032), Warfarin 2.26 (95 % CI, 2.05-2.51, P < 0.001), DOACs 1.99 (95 % CI, 1.43-2.76, P < 0.001) were related to elevated mortality. Dose-response meta-analysis of age found an odds ratio of 1.029 (95 % CI, 1.024-1.034, P < 0.001) for every 1-year increase in age on in-hospital mortality. CONCLUSIONS: In the field of elderly patients with TBI, the overall in-hospital mortality and its temporal-spatial feature, the subgroup in-hospital mortalities according to injury severity, and dose-response meta-analysis of age were firstly comprehensively summarized. Substantial key risk factors, including the ones previously not elucidated, were identified. Our study is thus of help in underlining the importance of treating elderly TBI, providing useful information for healthcare providers, and initiating future management guidelines. This work underscores the necessity of integrating elderly TBI treatment and management into broader health strategies to address the challenges posed by the aging global population. REVIEW REGISTRATION: PROSPERO CRD42022323231.

Efficacy and Safety of Vonoprazan-Based Quadruple Therapy for the Eradication of Helicobacter pylori in Patients with Peptic Ulcers: A Pooled Analysis of Two Randomized, Double-Blind, Double-Dummy, Phase 3 Trials.

Helicobacter pylori eradication is crucial in the treatment of peptic ulcers caused by H. pylori infection, a disease highly prevalent in Asia. We present a pooled analysis of two randomized, double-blind, double-dummy, phase 3 studies evaluating the efficacy and safety of vonoprazan-based bismuth-containing quadruple therapy for H. pylori eradication. Patients aged ≥18 years with endoscopically confirmed duodenal or gastric ulcers were randomized 1 : 1 to receive vonoprazan 20 mg or lansoprazole 30 mg once daily for up to 6 (duodenal ulcers) or 8 weeks (gastric ulcers). H. pylori-positive patients received vonoprazan- or lansoprazole-based bismuth-containing quadruple therapy for the first 2 weeks. H. pylori eradication was determined using the carbon-13 urea breath test at a follow-up visit 4 weeks post-treatment. The H. pylori eradication rate was 90.6% with vonoprazan vs. 85.2% with lansoprazole (difference: 5.4%; 95% confidence interval (CI): -0.1, 10.8). H. pylori eradication rates were 7.1% (95% CI: 1.4, 12.8) and 12.6% (95% CI: 3.9, 22.0) higher in patients aged <65 years and current smokers, respectively, with vonoprazan vs. lansoprazole. In the Chinese subpopulation, the H. pylori eradication rate was 92.0% with vonoprazan vs. 86.0% with lansoprazole (difference: 6.1%; 95% CI: 0.5, 11.7). Treatment-emergent adverse events occurred in 72.7 vs. 62.6% of H. pylori-positive patients at baseline in the vonoprazan vs. lansoprazole arm. H. pylori eradication with vonoprazan-based quadruple therapy was noninferior to lansoprazole-based quadruple therapy and exceeded 90%, a clinically relevant threshold for determining the efficacy of H. pylori eradication regimens (ClinicalTrials.gov identifier: NCT03050359; NCT03050307).

Multi-kernel support vector regression with improved moth-flame optimization algorithm for software effort estimation.

In this paper, a novel Moth-Flame Optimization (MFO) algorithm, namely MFO algorithm enhanced by Multiple Improvement Strategies (MISMFO) is proposed for solving parameter optimization in Multi-Kernel Support Vector Regressor (MKSVR), and the MISMFO-MKSVR model is further employed to deal with the software effort estimation problems. In MISMFO, the logistic chaotic mapping is applied to increase initial population diversity, while the mutation and flame number phased reduction mechanisms are carried out to improve the search efficiency, as well the adaptive weight adjustment mechanism is used to accelerate convergence and balance exploration and exploitation. The MISMFO model is verified on fifteen benchmark functions and CEC 2020 test set. The results show that the MISMFO has advantages over other meta-heuristic algorithms and MFO variants in terms of convergence speed and accuracy. Additionally, the MISMFO-MKSVR model is tested by simulations on five software effort datasets and the results demonstrate that the proposed model has better performance in software effort estimation problem. The Matlab code of MISMFO can be found at https://github.com/loadstar1997/MISMFO .