Cigarette Smoke Extract-Treated Mouse Airway Epithelial Cells-Derived Exosomal LncRNA MEG3 Promotes M1 Macrophage Polarization and Pyroptosis in Chronic Obstructive Pulmonary Disease by Upregulating TREM-1 via m6A Methylation.

Cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs)-derived exosomes accelerate the progression of chronic obstructive pulmonary disease (COPD) by upregulating triggering receptor expressed on myeloid cells 1 (TREM-1); however, the specific mechanism remains unclear. We aimed to explore the potential mechanisms of CSE-treated MAECs-derived exosomes on M1 macrophage polarization and pyroptosis in COPD. In vitro, exosomes were extracted from CSE-treated MAECs, followed by co-culture with macrophages. In vivo, mice exposed to cigarette smoke (CS) to induce COPD, followed by injection or/and intranasal instillation with oe-TREM-1 lentivirus. Lung function and pathological changes were evaluated. CD68+ cell number and the levels of iNOS, TNF-α, IL-1ß (M1 macrophage marker), and pyroptosis-related proteins (NOD-like receptor family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-1 recruitment domain, caspase-1, cleaved-caspase-1, gasdermin D [GSDMD], and GSDMD-N) were examined. The expression of maternally expressed gene 3 (MEG3), spleen focus forming virus proviral integration oncogene (SPI1), methyltransferase 3 (METTL3), and TREM-1 was detected and the binding relationships among them were verified. MEG3 increased N6-methyladenosine methylation of TREM-1 by recruiting SPI1 to activate METTL3. Overexpression of TREM-1 or METTL3 negated the alleviative effects of MEG3 inhibition on M1 polarization and pyroptosis. In mice exposed to CS, EXO-CSE further aggravated lung injury, M1 polarization, and pyroptosis, which were reversed by MEG3 inhibition. TREM-1 overexpression negated the palliative effects of MEG3 inhibition on COPD mouse lung injury. Collectively, CSE-treated MAECs-derived exosomal long non-coding RNA MEG3 may expedite M1 macrophage polarization and pyroptosis in COPD via the SPI1/METTL3/TREM-1 axis.

An investigative meta-analysis on the effectiveness and safety of integrating VEGF/VEGFR inhibitors with PD-1/PD-L1 inhibitors in cases with R/M HNSCC.

OBJECTIVES: Exploration into the use of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) inhibitors alongside programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has been undertaken for treating recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). We conducted a meta-analysis to provide a more precise assessment of the efficacy and safety of this integrated approach in managing R/M HNSCC. METHODS: A systematic exploration encompassing PubMed, Embase, the Cochrane Library, and Web of Science databases was undertaken to figure out relevant studies. It was attempted to analyze critical endpoints, such as overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) utilizing a random-effects model. RESULTS: Eleven studies, encompassing 413 patients, were analyzed. The combined data revealed an ORR of 41 % (95 % CI: 34-49 %), a DCR of 67 % (95 % CI: 51-83 %), a median PFS of 5.87 months (95 % CI: 3.90-7.85), and a median OS of 9.63 months (95 % CI: 6.78-12.49). Furthermore, the rates for 1-year PFS and OS were 45 % (95 % CI: 27-64 %) and 65 % (95 % CI: 49-81 %), respectively. The occurrence of grade 3 or higher adverse events related to the drugs was 20 % (95 % CI: 10-30 %). Subgroup analysis within the tyrosine kinase inhibitor (TKI) group revealed an ORR of 47 % (95 % CI: 39 %-55 %) and a DCR of 67 % (95 % CI: 46 %-88 %). CONCLUSIONS: In summary, combining VEGF/VEGFR inhibitors with PD-1/PD-L1 inhibitors shows considerable effectiveness with manageable side effects in cases with R/M HNSCC. SYSTEMATIC REVIEW REGISTRATION: Registered with the International Prospective Register of Systematic Reviews, identifier CRD42023486345.

A combined model using pre-treatment CT radiomics and clinicopathological features of non-small cell lung cancer to predict major pathological responses after neoadjuvant chemoimmunotherapy.

OBJECTIVE: To investigate the relationship between clinical pathological characteristics, pretreatment CT radiomics, and major pathologic response (MPR) of non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy, and to establish a combined model to predict the major pathologic response of neoadjuvant chemoimmunotherapy. METHODS: A retrospective study of 211 patients with NSCLC who underwent neoadjuvant chemoimmunotherapy and surgical treatment from January 2019 to April 2021 was conducted. The patients were divided into two groups: the MPR group and the non-MPR group. Pre-treatment CT images were segmented using ITK SNAP software to extract radiomics features using Python software. Then a radiomics model, a clinical model, and a combined model were constructed and validated using a receiver operating characteristic (ROC) curve. Finally, Delong's test was used to compare the three models. RESULTS: The radiomics model achieved an AUC of 0.70 (95 % CI: 0.62-0.78) in the training group and 0.60 (95 % CI: 0.45-0.76) in the validation group. RECIST assessment results were screened from all clinical characteristics as independent factors for MPR with multivariate logistic regression analysis. The AUC of the clinical model for predicting MPR was 0.66 (95 % CI: 0.59-0.73) in the training group and 0.77 (95 % CI: 0.66-0.87) in the validation group. The combined model with combined radiomics and clinicopathological characteristics achieved an AUC was 0.76 (95 % CI: 0.68-0.84) in the training group, and 0.80 (95 % CI: 0.67-0.92) in the validation group. Delong's test showed that the AUC of the combined model was significantly higher than that of the radiomics model alone in both the training group (P = 0.0067) and the validation group (P = 0.0009).The calibration curve showed good agreement between predicted and actual MPR. Clinical decision curve analysis showed that the combined model was superior to radiomics alone. CONCLUSIONS: Radiomics model can predict MPR in NSCLC after neoadjuvant chemoimmunotherapy with similar accuracy to RECIST assessment criteria. The combined model based on pretreatment CT radiomics and clinicopathological features showed better predictive power than independent radiomics model or independent clinicopathological features, suggesting that it may be more useful for guiding personalized neoadjuvant chemoimmunotherapy treatment strategies.

Stromal B Lymphocytes Affecting Prognosis in Triple-Negative Breast Cancer by Opal/TSA Multiplexed Immunofluorescence.

Objective: Immune cells play a key role in tumor microenvironment. The purpose of this study was to investigate the infiltration and clinical indication of immune cells including their combined prognostic value in microenvironment of triple negative breast cancer. Methods: We investigated 100 patients with triple negative breast cancer by Opal/Tyramide Signal Amplification multispectral immunofluorescence between 2003 and 2017 at Zhejiang Provincial people's Hospital. Intratumoral and stromal immune cells of triple negative breast cancer were classified and quantitatively analyzed. Survival outcomes were compared using the Kaplan-Meier method and further analyzed with multivariate analysis. Results: Infiltration level of stromal B lymphocytes, stromal and intratumoral CD8+ T cells, stromal CD4+ T cells, stromal PD-L1 and intratumoral tumor associated macrophages 2 cells were shown as independent factors affecting disease-free survival and overall survival in univariate analysis. Stromal B lymphocytes, T stage, N stage and pathological type were independent predictive factors for both DFS and OS in multivariate analysis. We firstly found that patients with B lymphocytes-enriched subtypes have a better prognosis than those with T lymphocytes-enriched subtypes and tumor-associated macrophage-enriched subtypes. Conclusion: The present study identified a bunch of immune targets and subtypes, which could be exploited in future combined immunotherapy/chemotherapy strategies for triple negative breast cancer patients.

Application of interpretable machine learning algorithms to predict distant metastasis in ovarian clear cell carcinoma.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. METHODS: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). RESULTS: In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762-0.823), 0.904 (0.835-0.973), 0.759 (0.731-0.787), 0.221 (0.186-0.256), 0.974 (0.967-0.982), 0.353 (0.306-0.399), and 0.834 (0.696-0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753-0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. CONCLUSIONS: This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions.

Smoking and idiopathic pulmonary fibrosis: A meta-analysis.

INTRODUCTION: In this study, we aimed to systematically explore the relationship between smoking and idiopathic pulmonary fibrosis (IPF). METHODS: The PubMed, Web of Science and Embase databases were searched to systematically identify eligible studies. The Newcastle‒Ottawa Quality Assessment Scale (NOS) was used to evaluate the quality of the selected studies. The pooled odds ratio (OR) and survival hazard ratio (HR) were calculated with a random effects model using Stata 16.0 software. RESULTS: Thirty studies were enrolled. All of the included studies were considered to have intermediate or high quality. Nine studies were suitable for meta-analysis of ORs, and twenty-one studies were suitable for meta-analysis of survival HR. The pooled analysis revealed a significant difference in the risk of IPF between the smoking group and the never smoking group (OR 1.71, 95% CI 1.27-2.30, P < 0.001), indicating that smoking is a risk factor for IPF. When analyzing pooled survival HRs, never smoking was compared to former smoking or current smoking. Former smoking was shown to be a poor prognostic factor for IPF (HR 1.43, 95% CI 1.18-1.74, P < 0.001), but current smoking was not a significant factor. CONCLUSIONS: Our results indicated that smoking is a risk factor for IPF patients. IMPLICATIONS: In this study, we mainly concluded that smoking is a risk factor for IPF and that former smoking is a poor prognostic factor for IPF. To our knowledge, this is the first meta-analysis report focusing on the association between smoking per se and IPF. Through our current study, we hope to further raise awareness of the relationship between smoking and IPF.

Acupressure bladder meridian alleviates anxiety disorder in rats by regulating MAPK and BDNF signal pathway.

The aim of this study was to investigate the effects of acupressure bladder meridian (ABM) on anxiety in rats. Chronic stress was induced rats to establish rat anxiety model. Shuttle experiment and open field experiments of were used to measure behaviors. The levels of cytokines in serum and hippocampus of rats were detected. Brain neurotransmitters (dopamine, 5- hydroxy tryptamine, norepinephrine) were detected by Enzyme linked immunosorbent assay (ELISA) kits. Immunohistochemistry and western blotting were used to detect MAPK and BDNF signal pathway in hippocampus of rats. ABM significantly improve behaviors, decreased cytokine levels in serum and hippocampus. ABM restored the changes of neurotransmitters and significantly decreased protein expressions of MAPK signal pathway and increased protein expressions of BDNF signal pathway in hippocampus of rats. The results shown that ABM significantly improved anxiety via inhibition of MAPK signal pathway and increased BDNF signal pathway.

[Research progress of novel functional materials in extraction of algal toxins].

Algal toxins are secondary metabolites produced by harmful algae; these metabolites are characterized with strong toxicity, diverse structure and bioaccumulation. Aquatic organisms that feed on harmful algae can accumulate algal toxins in their bodies, and the consumption of these organisms by humans can cause symptoms of paralysis, diarrhea, and even death. The onset of poisoning can occur within as little as 30 min; in many cases, no suitable antidote for algal toxins is available. Thus, algal toxins present significant threats to human health, the aquaculture industry, and aquatic ecosystems. Because the potential risks of algal toxins are a critical issue, these toxins have become a research hotspot. The water environment and various types of aquatic products should be monitored and analyzed to ensure their safety. However, because of possible matrix effects and the low content of algal toxins in actual samples, an efficient pretreatment method is necessary prior to instrumental analyses. Efficient sample pretreatment techniques can not only reduce or eliminate interferences from the sample matrix during analysis but also enrich the target analytes to meet the detection limit of the analytical instrument, thereby ensuring the sensitivity and accuracy of the detection method. In recent years, sample pretreatment techniques such as solid-phase extraction (SPE), solid-phase microextraction (SPME), magnetic SPE (MSPE), dispersive SPE (DSPE), and pipette tip-based SPE (PT-SPE) have gained wide attention in the field of algal-toxin separation and analysis. The performance of these pretreatment techniques largely depends on the characteristics of the extraction materials. Given the diverse physicochemical properties of algal toxins, including their different molecular sizes, hydrophobicity/hydrophilicity, and charges, the design and preparation of materials suitable for algal-toxin extraction is an essential undertaking. The optimal extraction material should be capable of reversible algal-toxin adsorption and preferably possess a porous structure with a large surface area to allow for high recovery rates and good interfacial contact with the toxins. Additionally, the extraction material should exhibit good chemical stability in the sample solution and elution solvent within the working pH range; otherwise, it may dissolve or lose its functional groups. Many research efforts have sought to develop novel adsorbent materials with these properties in the separation and analysis of algal toxins, focusing on carbon-based materials, metal organic frameworks (MOFs), covalent organic frameworks (COFs), molecularly imprinted polymers (MIPs), and their functionalized counterparts. Carbon-based materials, MOFs, and COFs have advantages such as large surface areas and abundant adsorption sites. These extraction materials are widely used in the separation and analysis of target substances in complex environmental, biological, and food samples owing to their excellent performance and unique microstructure. They are also the main adsorbents used for the extraction of algal toxins. These extraction materials play an essential role in the extraction of algal toxins, but they also present a number of limitations: (1) Carbon-based materials, MOFs, and COFs have relatively poor selective-adsorption ability towards target substances; (2) Most MOFs are unstable in aqueous solutions and challenging to apply during extraction from water-based sample solutions; (3) COFs mainly consist of lightweight elements, rendering them difficult to completely separate from sample solutions using centrifugal force, which limits their application range; (4) Although MIPs have good selectivity, issues such as template-molecule loss, slow mass-transfer rates, and low adsorption capacity must be addressed. Therefore, the design and preparation of novel functionalized extraction materials specifically tailored for algal toxins and studies on new composite extraction materials are highly desirable. This article collects representative literature from domestic and international research on algal-toxin analysis over the past decade, summarizes the relevant findings, categorizes the applications of novel functional materials in algal-toxin-extraction processes, and provides an outlook on their future development prospects.

Chinese medicine Phragmites communis (Lu Gen) for acute respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials.

Background: Acute respiratory tract infections (ARTIs) are the most common cause of morbidity and mortality worldwide, with most people experiencing at least one episode per year. Current treatment options are mainly symptomatic therapy. Antivirals, antibiotics, and glucocorticoids are of limited benefit for most infections. Traditional Chinese medicine has shown potential benefits in the treatment of ARTIs. Objective: The objective of this study was to determine the efficacy, effectiveness, and safety of Phragmites communis Trin. (P. communis, a synonym of Phragmites australis (Cav.) Trin. ex Steud) as monotherapy or as part of an herb mixture for ARTIs. Method: Eight databases and two clinical trial registries were searched from inception to 8 February 2023 for randomized controlled trials (RCTs) evaluating any preparation involving P. communis without language restrictions. The Risk of Bias Tool 2.0 was used to assess the risk of bias of the included trials. RevMan 5.3 software was used for data analyses with effects estimated as risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% confidence intervals (CIs). The online GRADEpro tool was used to assess the certainty of the evidence, if available. Results: Forty-two RCTs involving 6,879 patients with ARTIs were included, with all trials investigating P. communis as part of an herbal mixture. Of the included trials, the majority (38/42) were considered high risk. Compared to the placebo, P. communis preparations improved the cure rate [RR = 1.60, 95% CI (1.13, 2.26)] and fever clearance time [MD = -2.73 h, 95% CI (-4.85, -0.61)]. Compared to usual care alone, P. communis preparations also significantly improved the cure rate [RR = 1.57, 95% CI (1.36, 1.81)] and fever clearance time [SMD = -1.24, 95% CI (-2.37, -0.11)]. P. communis preparations plus usual care compared to usual care alone increased the cure rate [RR = 1.55, 95% CI (1.35, 1.78)], shortened the fever clearance time [MD = -19.31 h, 95% CI (-33.35, -5.27)], and improved FEV1 [ MD = 0.19 L, 95% CI (0.13, 0.26)] and FVC [ MD = 0.16 L, 95% CI (0.03, 0.28)]. Conclusion: Low- or very low-certainty evidence suggests that P. communis preparations may improve the cure rate of ARTIs, shorten the fever clearance time in febrile patients, and improve the pulmonary function of patients with acute exacerbation of chronic obstructive pulmonary disease or chronic bronchitis. However, these findings are inconclusive and need to be confirmed in rigorously designed trials. Systematic review registration: PROSPERO, identifier CRD42021239936.

The effects of manual therapy in pain and safety of patients with knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Manual therapy (MT) is frequently used in combination with management of osteoarthritis of the knee, but there is no consensus on the exact efficacy of this treatment strategy. The purpose of this systematic review and meta-analysis was to evaluate the pain relief and safety of MT for treatment of knee osteoarthritis (KOA). METHODS: Randomized controlled trials evaluating MT in patients with KOA in major English and Chinese journals were searched in the following databases: Wanfang, China Science and Technology Journal Database (VIP database), China National Knowledge Infrastructure (CNKI), PubMed, Embase, Web of Science, and the Cochrane Library databases through June 2023. The methodological quality and quality of evidence of the included studies were assessed using Cochrane's risk-of-bias 2 (ROB 2) tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Data analysis was performed using Stata version 15.0 software. After use of Galbraith plots to exclude studies that could lead to heterogeneity, random effects models were used to analyze the remaining data and test the consistency of the findings. We used meta-regression to assess the effect of treatment period, patient age, and sex ratio on outcomes. Funnel plots and Egger's test were used to evaluate publication bias. Sensitivity analyses were used to determine the reliability of the results. RESULTS: A total of 25 studies, with 2376 participants, were included in this review. The overall methodological quality of the included studies was limited. Our findings suggest that MT has a positive impact on pain relief outcomes in KOA patients. The meta-analysis showed that MT was superior to usual care (SMD = 2.04, 95% CI 0.94, 3.14, I 2 = 96.3%; low evidence quality) and exercise (SMD = 1.56, 95% CI 0.41, 2.71, I 2 = 96.3%; low evidence quality) for reducing pain. In terms of improvement in visual analogue scale (VAS) scores, MT treatment beyond 4 weeks (SMD = 1.56, 95% CI 0.41, 2.71, I 2 = 96.3%) may be superior to treatments less than or equal to 4 weeks (SMD = 1.24, 95% CI 0.56, 1.95, I 2 = 94.7%). No serious adverse events associated with MT were reported. CONCLUSIONS: MT may be effective at reducing pain in patients with KOA and may be more effective after a 4-week treatment period. Compared with usual care and exercise therapy, MT may be superior at reducing KOA pain in the short term (9 weeks), but its long-term efficacy requires careful consideration of evidence-based outcomes. MT appears to be safe for KOA patients, though clinicians should inform patients of the potential risk of MT-related adverse events.

Cost-effective prognostic evaluation of breast cancer: using a STAR nomogram model based on routine blood tests.

Background: Breast cancer (BC) is the most common and prominent deadly disease among women. Predicting BC survival mainly relies on TNM staging, molecular profiling and imaging, hampered by subjectivity and expenses. This study aimed to establish an economical and reliable model using the most common preoperative routine blood tests (RT) data for survival and surveillance strategy management. Methods: We examined 2863 BC patients, dividing them into training and validation cohorts (7:3). We collected demographic features, pathomics characteristics and preoperative 24-item RT data. BC risk factors were identified through Cox regression, and a predictive nomogram was established. Its performance was assessed using C-index, area under curves (AUC), calibration curve and decision curve analysis. Kaplan-Meier curves stratified patients into different risk groups. We further compared the STAR model (utilizing HE and RT methodologies) with alternative nomograms grounded in molecular profiling (employing second-generation short-read sequencing methodologies) and imaging (utilizing PET-CT methodologies). Results: The STAR nomogram, incorporating subtype, TNM stage, age and preoperative RT data (LYM, LYM%, EOSO%, RDW-SD, P-LCR), achieved a C-index of 0.828 in the training cohort and impressive AUCs (0.847, 0.823 and 0.780) for 3-, 5- and 7-year OS rates, outperforming other nomograms. The validation cohort showed similar impressive results. The nomogram calculates a patient's total score by assigning values to each risk factor, higher scores indicating a poor prognosis. STAR promises potential cost savings by enabling less intensive surveillance in around 90% of BC patients. Compared to nomograms based on molecular profiling and imaging, STAR presents a more cost-effective, with potential savings of approximately $700-800 per breast cancer patient. Conclusion: Combining appropriate RT parameters, STAR nomogram could help in the detection of patient anemia, coagulation function, inflammation and immune status. Practical implementation of the STAR nomogram in a clinical setting is feasible, and its potential clinical impact lies in its ability to provide an early, economical and reliable tool for survival prediction and surveillance strategy management. However, our model still has limitations and requires external data validation. In subsequent studies, we plan to mitigate the potential impact on model robustness by further updating and adjusting the data and model.

Efficacy and safety of traditional Chinese manual therapy (Tuina) in patients with non-specific chronic low back pain: a study protocol for a randomised controlled trial.

INTRODUCTION: Non-pharmacological interventions play a crucial role in the management of non-specific chronic low back pain (NSCLBP). One prime example is Tuina, a traditional Chinese manual therapy that incorporates pressing, kneading and rubbing techniques to alleviate physical discomfort and enhance overall well-being. It serves as a widely used technique in China and other East Asian countries. However, the effectiveness and safety of Tuina for managing NSCLBP have not been substantiated through rigorous clinical research. We sought to carry out a randomised controlled trial with an open-label design, blinded assessors and parallel arms to assess the effectiveness and safety of Tuina as a treatment for NSCLBP. The trial aims to provide high-quality evidence regarding the efficacy and safety of Tuina in improving outcomes for patients with NSCLBP. METHODS AND ANALYSIS: A total of 150 patients aged 18-60 years with NSCLBP will be recruited. Participants will be randomly assigned to one of the two groups. Both groups will receive standard health education. In addition, the treatment group will receive Tuina therapy, while the control group will participate in core stability exercises. Each group will undergo a total of 18 interventions over 6 weeks, with the interventions administered three times per week. The primary outcome measure is the patient's pain intensity, assessed using the Numerical Rating Scale, at week 6 following randomisation. Secondary outcomes encompass disability (measured by the Roland-Morris Disability Questionnaire), quality of life (assessed using the EuroQoL-5 dimensions questionnaire), adverse emotions (evaluated with the Pain Catastrophizing Scale, Tampa Scale of Kinesiophobia and Depression Anxiety Stress Scale), biomechanical outcomes, socioeconomic indicators (medication use, healthcare utilisation and absenteeism), patient satisfaction, treatment adherence and other relevant factors.The statistical analysis will follow the intention-to-treat principle. Two-way repeated measures analysis of variance will be used to compare the clinical data across different time points within both groups. ETHICS AND DISSEMINATION: The study protocol has received approval from the Ethics Committee of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine (2023-1366-133-01). All study participants will be required to give written informed consent. The findings of the study will be submitted to a peer-reviewed journal for publication and presented at scientific conferences. Additionally, the participants will receive copies of the results. TRIAL REGISTRATION NUMBER: ChiCTR2300076257.

Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses.

The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.

Monitoring the Season-Prevalence Relationship of Vairimorpha ceranae in Honey Bees (Apis mellifera) over One Year and the Primary Assessment of Probiotic Treatment in Taichung, Taiwan.

Microsporidiosis, which is caused by the pathogen Vairimorpha ceranae, is a prevalent disease in the honey bee (Apis mellifera) and might lead to significant adult honey bee mortality. In this study, we conducted an annual survey of the mature spore load of V. ceranae in the guts of nurse bees and forager bees in the apiary of National Chung Hsing University (NCHU) in Taiwan. The results indicated that, on average, honey bees hosted approximately 2.13 × 106 mature spore counts (MSCs)/bee in their guts throughout the entire year. The highest number of MSCs was 6.28 × 106 MSCs/bee, which occurred in April 2020, and the lowest number of MSCs was 5.08 × 105 MSCs/bee, which occurred in November 2020. Furthermore, the guts of forager bees had significantly higher (>58%) MSCs than those of nurse bees. To evaluate the potential of the probiotic to treat microsporidiosis, the lactic acid bacterium Leuconostoc mesenteroides TBE-8 was applied to honey bee colonies. A significant reduction (>53%) in MSCs following probiotic treatment was observed, indicating the potential of probiotic treatment for managing microsporidiosis. This research provided information on V. ceranae MSCs in the honey bee gut at NCHU in Taiwan and the MSCs' correlation with the annual season. Furthermore, a potential probiotic treatment for microsporidiosis was assessed for future management.

Toll-like receptor 2 deficiency promotes the generation of alloreactive γδT17 cells after cardiac transplantation in mice.

Homograft rejection is the main cause of heart transplantation failure. The role of TLR2, a major member of the toll-like receptor (TLR) family, in transplantation rejection is has yet to be elucidated. In this study, we used a mouse model of acute cardiac transplantation rejection to investigate whether the TLR2 signalling pathway can regulate cardiac transplantation rejection by regulating alloreactive IL-17+γδT (γδT17) cells. We found that the expression of TLR2 on the surface of dendritic cells (DCs) and macrophages increased during acute transplantation rejection. In addition, our investigation revealed that γδT17 cells exert a significant influence on acute cardiac transplantation rejection. TLR2 gene knockout resulted in an increase in alloreactive γδT17 cells in the spleen and heart grafts of recipient mice compared with wild-type recipient mice and an increase in the mRNA expression of IL-17, IL-1ß, CCR6, and CCL20 in the heart grafts. In an in vitro experiment, a mixed lymphocyte reaction was conducted to assess the impact of TLR2 deficiency on the generation of γδT17 cells, which further substantiated a significant increase compared to that in wild-type controls. Furthermore, the mixed lymphocyte reaction showed that TLR2 regulated the production of γδT17 cells by regulating the ability of DCs to secrete IL-1ß. These results suggest that TLR2 signalling is important for regulating the generation of γδT17 cells after cardiac allograft transplantation.

A Novel DNBS-based Fluorescent Probe for the Detection of H2S in Cells and on Test Strips.

Hydrogen sulfide (H2S) plays a key role in the physiology and pathology of organisms, and H2S in the environment is easily absorbed and harmful to health. It is of great significance to develop a probe with good selectivity, high sensitivity and good stability that can detect hydrogen sulfide inside and outside organisms. In this work, we designed a novel "turn-on" fluorescent probe CIM-SDB for the detection of H2S. The probe CIM-SDB used indene-carbazole as the fluorophore and 2,4-dinitrobenzenesulfonyl as the recognition site. The probe CIM-SDB exhibited high selectivity and sensitivity to H2S (detection limit as low as 123 nM). Moreover, the probe CIM-SDB was successfully applied to the detection of intracellular exogenous and endogenous H2S, and the test strips prepared by the probe CIM-SDB could realize the convenient and rapid detection of H2S.

A nomogram to predict lung cancer in pulmonary lesions for tuberculosis infection patients.

Similar clinical features make the differential diagnosis difficult, particularly between lung cancer and pulmonary tuberculosis (TB), without pathological evidence for patients with concomitant TB infection. Our study aimed to build a nomogram to predict malignant pulmonary lesions applicable to clinical practice. We retrospectively analyzed clinical characteristics, imaging features, and laboratory indicators of TB infection patients diagnosed with lung cancer or active pulmonary TB at Xiangya Hospital of Central South University. A total of 158 cases from January 1, 2018 to May 30, 2019 were included in the training cohort. Predictive factors for lung cancer were screened by a multiple-stepwise logistic regression analysis. A nomogram model was established, and the discrimination, stability, and prediction performance of the model were analyzed. A total of 79 cases from June 1, 2019, to December 30, 2019, were used as the validation cohort to verify the predictive value of the model. Eight predictor variables, including age, pleural effusion, mediastinal lymph node, the number of positive tumor markers, the T cell spot test for TB, pulmonary lesion morphology, location, and distribution, were selected to construct the model. The corrected C-statistics and the Brier scores were 0.854 and 0.130 in the training cohort, and 0.823 and 0.163 in the validation cohort. Calibration plots showed good performance, and decision curve analysis indicated a high net benefit. In conclusion, the nomogram model provides an effective method to calculate the probability of lung cancer in TB infection patients, and it has excellent discrimination, stability, and prediction performance in detecting a malignant diagnosis of undiagnosed pulmonary lesions.

Continuous Detection of Cobalt Ions and Pyrophosphates by NAC-CdTe Quantum Dots Fluorescence Probes.

In this work, a simple and sensitive N-acetyl-L-cysteine (NAC)-covered CdTe quantum dots (NAC-CdTe QDs) fluorescence probe for continuous detection of Co2+ and pyrophosphate ions (PPi, P2O74-) was synthesized. The fluorescence of the quantum dots was significantly quenched by Co2+ through the coordination of Co2+ and the carboxyl groups on the NAC-CdTe quantum dots. Interestingly, the combination of NAC-CdTe quantum dots with Co2+ yields a new fluorescence probe of Co2+-modified NAC-CdTe QDs (Co2+@NAC-CdTe). The addition of PPi restored the fluorescence due to the competition between PPi and carboxyl groups with Co2+ causing Co2+ to detach from the surface of Co2+@NAC-CdTe quantum dots. Thus, a sensitive and reversible detection of Co2+ and PPi had been successfully established. The Co2+@NAC-CdTe quantum dots fluorescence probe exhibits excellent selectivity and high sensitivity toward PPi detection with low detection limit of 0.28 µM. In addition, the novel fluorescence probe was successfully applied to detect the concentration of PPi in environmental water samples and in-vitro cells imaging.

Drp1: Focus on Diseases Triggered by the Mitochondrial Pathway.

Drp1 (Dynamin-Related Protein 1) is a cytoplasmic GTPase protein encoded by the DNM1L gene that influences mitochondrial dynamics by mediating mitochondrial fission processes. Drp1 has been demonstrated to play an important role in a variety of life activities such as cell survival, proliferation, migration, and death. Drp1 has been shown to play different physiological roles under different physiological conditions, such as normal and inflammation. Recently studies have revealed that Drp1 plays a critical role in the occurrence, development, and aggravation of a series of diseases, thereby it serves as a potential therapeutic target for them. In this paper, we review the structure and biological properties of Drp1, summarize the biological processes that occur in the inflammatory response to Drp1, discuss its role in various cancers triggered by the mitochondrial pathway and investigate effective methods for targeting Drp1 in cancer treatment. We also synthesized the phenomena of Drp1 involving in the triggering of other diseases. The results discussed herein contribute to our deeper understanding of mitochondrial kinetic pathway-induced diseases and their therapeutic applications. It is critical for advancing the understanding of the mechanisms of Drp1-induced mitochondrial diseases and preventive therapies.

Diagnostic value of Video Electroencephalography combined with Magnetic Resonance Imaging-diffusion tensor imaging in epilepsy.

Objective: To explore the diagnostic value of video electroencephalography (VEEG) combined with magnetic resonance imaging diffusion tensor imaging (MRI-DTI) in epilepsy. Methods: In this retrospective observational study, clinical data of 60 patients who underwent both VEEG and MRI examinations at the Neurosurgery Department of Quzhou People's Hospital from December 2020 to March 2023 were retrospectively reviewed, and a total of 55 patients were finally included. We evaluated the diagnostic value of combining VEEG and MRI to determine seizure type, location of epileptic focus, and structural abnormalities of brain tissue, using surgical and pathological results as the gold standard. Results: The accuracy of the combined approach for determining the seizure type was 98.18%, which was higher than the accuracy of MRI (85.45%, P<0.05) or VEEG (81.82%, P<0.05) alone. The accuracy of joint examination for lesion location was 100.00%, which was higher than those of MRI (85.45%, P<0.05) or VEEG (83.64%, P<0.05) alone. Similar abnormal brain tissue structure detection rates was found for both MRI and VEEG (P>0.05). Conclusions: The application of MRI-DTI combined with VEEG to diagnose patients with epilepsy allows for the identification of abnormal structural changes in brain and the location of lesions. Combining both approaches can improve the diagnostic accuracy of each technique alone and provide a reference for the formulation and adjustment of disease management plans.