The development and external validation of a web-based nomogram for predicting overall survival with Ewing sarcoma in children.

Background: Ewing sarcoma remains the second most prevalent primary aggressive bone tumor in teens and young adults. The aim of our study was to develop and validate a web-based nomogram to predict the overall survival for Ewing sarcoma in children. Methods: A total of 698 patients, with 640 cases from the Surveillance, Epidemiology, and End Results (the training set) and 58 cases (the external validation set), were included in this study. Cox analyses were carried out to determine the independent prognostic indicators, which were further included to establish a web-based nomogram. The predictive abilities were tested through the concordance index, calibration curve, decision curve analysis, and area under the receiver operating characteristic curve. Results: As suggested by univariate and multivariate Cox analyses, age, primary site, tumor size, metastasis stage (M stage), and chemotherapy were included as the independent predictive variables. The area under the receiver operating characteristic curve values, calibration curves, concordance index, and decision curve analysis from training and validation groups suggested the model has great clinical applications. Conclusion: We developed a convenient and precise web-based nomogram to evaluate overall survival for Ewing sarcoma in children. The application of this nomogram would assist physicians and patients in making decisions.

Genetically predicted mood swings increased risk of cardiovascular disease: Evidence from a Mendelian randomization analysis.

BACKGROUND: Mood swings is linked to a higher risk of cardiovascular diseases (CVDs). However, the causal relationships between them remain unknown. METHODS: We conducted this Mendelian randomization (MR) analysis to evaluate the causal associations between mood swings (n = 373,733) and 5 CVDs, including CAD, MI, HF, AF, and stroke using summary data of large-scale genome-wide association studies (GWAS). FinnGen datasets validated the results. Various MR approaches, sensitivity analyses, multivariable MR (MVMR), and two-step MR mediation analyses were applied. RESULTS: The MR analysis revealed significant causal effects of mood swings on CAD (OR = 1.45, 95 % CI 1.24-1.71; P = 5.52e-6), MI (OR = 1.60, 95 % CI 1.32-1.95; P = 1.77e-6), HF (OR = 1.42, 95 % CI 1.18-1.71; P = 2.32e-4), and stroke (OR = 1.48, 95 % CI 1.19-1.83; P = 3.46e-4), excluding AF (P = 0.16). In the reverse MR analysis, no causal relationships were observed. The results were reproducible using FinnGen data. In the MVMR analysis, the causal effects of mood swings on CAD, MI, HF and stroke still remain significant after adjusting potential confounding factors including BMI, smoking and T2DM, but not for LDL and hypertension. Further mediation analysis indicated hypertension may mediate the causal pathways from mood swings to CAD (18.11 %, 95 % CI: 8.83 %-27.39 %), MI (16.40 %, 95 % CI: 7.93 %-24.87 %), HF (13.06 %, 95 % CI: 6.25 %-19.86 %), and stroke (18.04 %, 95 % CI: 8.73 %-27.34 %). CONCLUSION: Mood swings has a significant causal impact on the development of CAD, MI, HF, and stroke, partly mediated by hypertension.

Single-cell RNA sequencing in donor and end-stage heart failure patients identifies NLRP3 as a therapeutic target for arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Dilation may be the first right ventricular change and accelerates the progression of threatening ventricular tachyarrhythmias and heart failure for patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), but the treatment for right ventricular dilation remains limited. METHODS: Single-cell RNA sequencing (scRNA-seq) of blood and biventricular myocardium from 8 study participants was performed, including 6 end-stage heart failure patients with ARVC and 2 normal controls. ScRNA-seq data was then deeply analyzed, including cluster annotation, cellular proportion calculation, and characterization of cellular developmental trajectories and interactions. An integrative analysis of our single-cell data and published genome-wide association study-based data provided insights into the cell-specific contributions to the cardiac arrhythmia phenotype of ARVC. Desmoglein 2 (Dsg2)mut/mut mice were used as the ARVC model to verify the therapeutic effects of pharmacological intervention on identified cellular cluster. RESULTS: Right ventricle of ARVC was enriched of CCL3+ proinflammatory macrophages and TNMD+ fibroblasts. Fibroblasts were preferentially affected in ARVC and perturbations associated with ARVC overlap with those reside in genetic variants associated with cardiac arrhythmia. Proinflammatory macrophages strongly interact with fibroblast. Pharmacological inhibition of Nod-like receptor protein 3 (NLRP3), a transcriptional factor predominantly expressed by the CCL3+ proinflammatory macrophages and several other myeloid subclusters, could significantly alleviate right ventricular dilation and dysfunction in Dsg2mut/mut mice (an ARVC mouse model). CONCLUSIONS: This study provided a comprehensive analysis of the lineage-specific changes in the blood and myocardium from ARVC patients at a single-cell resolution. Pharmacological inhibition of NLRP3 could prevent right ventricular dilation and dysfunction of mice with ARVC.

Formation and toxicity contribution of chlorinated and dechlorinated halobenzoquinones from dichlorophenols after ozonation.

Halobenzoquinones (HBQs) are a class of disinfection byproducts with high cytotoxicity and potential carcinogenicity, which have been widely detected in chlorination of drinking water and swimming pool water. However, to date, the formation of HBQs upon ozonation and the HBQ precursors have been overlooked. This study investigated the formation of chlorinated and dechlorinated HBQs from six dichlorophenol (DCP) isomers. The monomeric and dimeric HBQs were identified in all the ozonation effluents, exhibiting 1-100 times higher toxicity levels than their precursors. The sum of detected HBQs intensity had a satisfactory linear relation with the maximum toxic unit (R2 = 0.9657), indicating the primary toxicity contribution to the increased overall toxicity of effluents. Based on density functional theory calculations, when ozone attacks the para carbon to the hydroxyl group of 2,3-DCP, the probability of producing chlorinated HBQs is 80.41 %, indicating that the para carbon attack mainly resulted in the formation of monomeric HBQs. 2,3-dichlorophenoxy radicals were successfully detected in ozonated 2,3-DCP effluent through electron paramagnetic resonance and further validated using theoretical calculation, revealing the formation pathway of dimeric HBQs. The results indicate that chlorinated phenols, regardless of the positions of chlorine substitution, can potentially serve as precursors for both chlorinated and dechlorinated HBQs formation during ozonation.

A cascade signal-amplified fluorescent biosensor combining APE1 enzyme cleavage-assisted target cycling with rolling circle amplification.

A cascade signal-amplified fluorescent biosensor was developed for miRNA-21 detection by combining APE1 enzyme-assisted target recycling and rolling circle amplification strategy. A key feature of this biosensor is its dual-trigger mechanism, utilizing both tumor-endogenous miRNA-21 and the APE1 enzyme in the initial amplification step, followed by a second rolling circle amplification reaction. This dual signal amplification cascade significantly enhanced sensitivity, achieving a detection limit of 3.33 pM. Furthermore, this biosensor exhibited excellent specificity and resistance to interference, allowing it to effectively distinguish and detect the target miRNA-21 in the presence of multiple interfering miRNAs. Moreover, the biosensor maintained its robust detection capabilities in a 10% serum environment, demonstrating its potential for clinical disease diagnosis applications.

Catheter-directed thrombolysis versus systemic anticoagulation in the treatment of symptomatic splanchnic venous thrombosis secondary to acute pancreatitis: a retrospective cohort study.

BACKGROUND: Catheter-directed thrombolysis (CDT) has been an important therapy and seems effective in patients with splanchnic venous thrombosis (SVT) secondary to some diseases, but this intervention hasn't been formally evaluated in the setting of acute pancreatitis (AP). METHODS: This was a retrospective study enrolled patients between January 2013 and December 2018. AP patients who developed SVT-induced symptoms, including intractable ascites and/or enteral nutrition intolerance, were included. Demographics, SVT associated parameters, clinical features and outcomes, long-term quality of life evaluated by using SF-36 questionnaire were compared between CDT group and systemic anticoagulation (SAC) group. RESULTS: 6 patients underwent CDT and 17 received SAC. Patients in CDT group had a higher recanalization rate (100% versus 35.3%; p = 0.014) and shorter time to symptoms resolution (median 8 days versus. 31.5 days, p = 0.004). Mortality and length of hospital stay were comparable between two groups. The association analysis indicated that CDT use exerted a significantly beneficial effect on recanalization rate (risk ratio, 2.833; 95% CI, 1.489 to 5.393; p = 0.002) and time to symptoms resolution (mean difference, -33.333; 95% CI, -64.612 to -2.055; p = 0.038). No SVT-related symptoms recurrence was recorded in survivors at six-month follow-up. There was no statistical difference in either item of SF-36 questionnaire between two groups. CONCLUSIONS: Compared with SAC, CDT may facilitate vascular recanalization and shorten symptom resolution for symptomatic SVT.

Role of Caveolin-1 on the molybdenum and cadmium exposure induces pulmonary ferroptosis and fibrosis in the sheep.

Molybdenum (Mo) is an essential trace element that exists in all tissues of the human body, but excessive Mo intake has a toxic effect. Cadmium (Cd) is a widely known and harmful heavy metal that exists in the environment. Although studies on Mo and Cd are available, it is still unknown how the combination of Mo and Cd causes pulmonary injury. Forty-eight sheep that were 2 months old were chosen and randomly separated into four groups as follows: Control group, Mo group, Cd group, and Mo + Cd group. The experiment lasted 50 days. The results showed that Mo and/or Cd caused significant pathological damage and oxidative stress in the lungs of sheep. Moreover, Mo and/or Cd exposure could downregulate the expression levels of xCT (SLC7A11 and SLC3A2), GPX4 and FTH-1 and upregulate the expression levels of PTGS2 and NCOA4, which led to iron overload and ferroptosis. Ferroptosis induced Wnt/ß-catenin-mediated fibrosis by elevating the expression levels of Caveolin-1 (CAV-1), Wnt 1, Wnt3a, ß-catenin (CTNNB1), TCF4, Cyclin D1, mmp7, α-SMA (ACTA2), Collagen 1 (COL1A1) and Vimentin. These changes were particularly noticeable in the Mo and Cd combination group. In conclusion, these data demonstrated that Mo and/or Cd exposure led to lung ferroptosis by inhibiting the SLC7A11/GSH/GPX4 axis, which in turn increases CAV-1 expression and subsequently activates the Wnt/ß-catenin pathway, leading to fibrosis in sheep lungs.

Effect of Low Dietary Folate on Mouse Spermatogenesis and Spindle Assembly Checkpoint Dysfunction May Contribute to Folate Deficiency-Induced Chromosomal Instability in Cultured Mouse Spermatogonia.

Folate, as the initial substrate in one-carbon metabolism, is involved in the synthesis of important substances such as DNA, RNA, and protein. Folate deficiency (FD) is associated with male subfertility and impaired spermatogenesis, yet the underlying mechanisms are poorly understood. In the present study, we established an animal model of FD to investigate the effect of FD on spermatogenesis. GC-1 spermatogonia were used as a model to investigate the effect of FD on proliferation, viability, and chromosomal instability (CIN). Furthermore, we explored the expression of core genes and proteins of spindle assembly checkpoint (SAC), a signaling cascade ensuring accurate chromosome segregation and preventing CIN during mitosis. Cells were maintained in medium containing 0, 20, 200, or 2000 nM folate for 14 days. CIN was measured by using a cytokinesis-blocked micronucleus cytome assay. We found that sperm counts decreased significantly (p < 0.001) and the rate of sperm with defects in the head increased significantly (p < 0.05) in FD diet mice. We also found, relative to the folate-sufficient conditions (2000 nM), cells cultured with 0, 20, or 200 nM folate exhibited delayed growth and increased apoptosis in an inverse dose-dependent manner. FD (0, 20, or 200 nM) significantly induced CIN (p < 0.001, p < 0.001, and p < 0.05, respectively). Moreover, FD significantly and inverse dose dependently increased the mRNA and protein expression of several key SAC-related genes. The results indicate that FD impairs SAC activity, which contributes to mitotic aberrations and CIN. These findings establish a novel association between FD and SAC dysfunction. Thus, FD-impaired spermatogenesis may be partly due to genomic instability and proliferation inhibition of spermatogonia.

Brown tumor of the cervical spine with primary hyperparathyroidism: A case report and literature review.

RATIONALE: Brown tumor (BT), an uncommon focal lytic bone tumor, is a non-neoplastic and reactive process caused by increased osteoclastic activity and fibroblastic proliferation in primary or secondary hyperparathyroidism. Vertebral tumor causing neural compression is relatively rare, especially in the cervical spine. PATIENT CONCERNS: A 29-year-old man developed neck pain and arm radicular pain 4 months ago, with the level of serum calcium significantly higher than normal. Computed tomography scan of the cervical spine revealed an expansile lytic lesion occupying the C6 body, left pedicle, and left lamina of C5-6. DIAGNOSES: Osteoclastoma according to imaging and histopathological results. INTERVENTIONS: A laminectomy of C5-6 was performed. OUTCOMES: One month later, he was re-hospitalized due to nausea and vomiting and the serum calcium, was still, kept at a high level. Additionally, the parathormone (PTH) was greatly higher than normal. BT with primary hyperparathyroidism due to the parathyroid tumor was considered. After the surgery of the right parathyroid gland was performed, serum calcium and PTH both decreased, and computed tomography showed good recovery. LESSONS: BTs might be misdiagnosed as other giant cell tumors, thus when giant cell tumors are considered, serum calcium and PTH examination may be needed to exclude BTs.

Analyzing bronchoalveolar fluid derived small extracellular vesicles using single-vesicle SERS for non-small cell lung cancer detection.

An emerging body of research by biologists and clinicians has demonstrated the clinical application of small extracellular vesicles (sEVs, also commonly referred to as exosomes) as biomarkers for cancer detections. sEVs isolated from various body fluids such as blood, saliva, urine, and cerebrospinal fluid have been used for biomarker discoveries with highly encouraging outcomes. Among the biomarkers discovered are those responsible for multiple cancer types and immune responses. These biomarkers are recapitulated from the tumor microenvironments. Yet, despite numerous discussions of sEVs in scientific literature, sEV-based biomarkers have so far played only a minor role for cancer diagnostics in the clinical setting, notably less so than other techniques such as imaging and biopsy. In this paper, we report the results of a pilot study (n = 10 from each of the patient and the control group) using bronchoalveolar lavage fluid to determine the presence of sEVs related to non-small cell lung cancer in twenty clinical samples examined using surface enhanced Raman spectroscopy (SERS).

Apoptin causes apoptosis in HepG-2 cells via Ca2+ imbalance and activation of the mitochondrial apoptotic pathway.

BACKGROUND: Apoptin is derived from the chicken anemia virus and exhibits specific cytotoxic effects against tumor cells. Herein, we found that Apoptin induced a strong and lasting endoplasmic reticulum (ER) stress response, Ca2+ imbalance, and triggered the mitochondrial apoptotic pathway. The aim of this study was to explore the mechanisms by which Apoptin exhibited anti-tumor effects in HepG-2 cells. METHODS: The intracellular levels of calcium (Ca2+ ) were induced by ER stress and determined by electron microscopy, flow cytometry, and fluorescence staining. The mitochondrial injury was determined by mitochondrial membrane potential and electron microscopy. Western blotting was used to investigate the levels of key proteins in ER stress and the apoptotic pathway in mitochondria. The relationship between Ca2+ levels and apoptosis in Apoptin-treated cells was analyzed using a Ca2+ chelator (BAPTA-AM), flow cytometry, and fluorescence staining. We also investigated the in vivo effects of Ca2+ imbalance on the mitochondrial apoptotic pathway using tumor tissues xenografted on nude mice. RESULTS: This study showed that Apoptin induced a strong and long- lasting ER stress and injury, which subsequently led to an imbalance of cellular Ca2+ levels, a reduction in the mitochondrial membrane potential, a significant extent image in the mitochondrial structure, and an increase in the expression levels of Smac/Diablo and Cyto-C. CONCLUSIONS: In summary, Apoptin induced apoptosis in HepG-2 cells via Ca2+ imbalance and activation of the mitochondrial apoptotic pathway. This study provided a new direction for antitumor research in Apoptin.

Cellular Landscapes of Nondiseased Human Cardiac Valves From End-Stage Heart Failure-Explanted Heart.

BACKGROUND: Exploring the mechanisms of valvular heart disease at the cellular level may be useful to identify new therapeutic targets; however, the comprehensive cellular landscape of nondiseased human cardiac valve leaflets remains unclear. METHODS: The cellular landscapes of nondiseased human cardiac valve leaflets (5 aortic valves, 5 pulmonary valves, 5 tricuspid valves, and 3 mitral valves) from end-stage heart failure patients undergoing heart transplantation were explored using single-cell RNA sequencing. Bioinformatics was used to identify the cell types, describe the cell functions, and investigate cellular developmental trajectories and interactions. Differences among the 4 types of cardiac valves at the cellular level were summarized. Pathological staining was performed to validate the key findings of single-cell RNA sequencing. An integrative analysis of our single-cell data and published genome-wide association study-based and bulk RNA sequencing-based data provided insights into the cell-specific contributions to calcific aortic valve diseases. RESULTS: Six cell types were identified among 128 412 cells from nondiseased human cardiac valve leaflets. Valvular interstitial cells were the largest population, followed by myeloid cells, lymphocytes, valvular endothelial cells, mast cells, and myofibroblasts. The 4 types of cardiac valve had distinct cellular compositions. The intercellular communication analysis revealed that valvular interstitial cells were at the center of the communication network. The integrative analysis of our single-cell RNA sequencing data revealed key cellular subpopulations involved in the pathogenesis of calcific aortic valve diseases. CONCLUSIONS: The cellular landscape differed among the 4 types of nondiseased cardiac valve, which might explain their differences in susceptibility to pathological remodeling and valvular heart disease.

Gold Nanopyramid Arrays for Non-Invasive Surface-Enhanced Raman Spectroscopy-Based Gastric Cancer Detection via sEVs.

Gastric cancer (GC) is one of the most common and lethal types of cancer affecting over one million people, leading to 768,793 deaths globally in 2020 alone. The key for improving the survival rate lies in reliable screening and early diagnosis. Existing techniques including barium-meal gastric photofluorography and upper endoscopy can be costly and time-consuming and are thus impractical for population screening. We look instead for small extracellular vesicles (sEVs, currently also referred as exosomes) sized ⌀ 30-150 nm as a candidate. sEVs have attracted a significantly higher level of attention during the past decade or two because of their potentials in disease diagnoses and therapeutics. Here, we report that the composition information of the collective Raman-active bonds inside sEVs of human donors obtained by surface-enhanced Raman spectroscopy (SERS) holds the potential for non-invasive GC detection. SERS was triggered by the substrate of gold nanopyramid arrays we developed previously. A machine learning-based spectral feature analysis algorithm was developed for objectively distinguishing the cancer-derived sEVs from those of the non-cancer sub-population. sEVs from the tissue, blood, and saliva of GC patients and non-GC participants were collected (n = 15 each) and analyzed. The algorithm prediction accuracies were reportedly 90, 85, and 72%. "Leave-a-pair-of-samples out" validation was further performed to test the clinical potential. The area under the curve of each receiver operating characteristic curve was 0.96, 0.91, and 0.65 in tissue, blood, and saliva, respectively. In addition, by comparing the SERS fingerprints of individual vesicles, we provided a possible way of tracing the biogenesis pathways of patient-specific sEVs from tissue to blood to saliva. The methodology involved in this study is expected to be amenable for non-invasive detection of diseases other than GC.

Apoptin mediates mitophagy and endogenous apoptosis by regulating the level of ROS in hepatocellular carcinoma.

BACKGROUND: Apoptin, as a tumor-specific pro-apoptotic protein, plays an important anti-tumoral role, but its mechanism of autophagy activation and the interaction between autophagy and apoptosis have not been accurately elucidated. Here, we studied the mechanism of apoptin-induced apoptosis and autophagy and the interaction between two processes. METHODS: Using crystal violet staining and the CCK-8 assay, we analyzed the effect of apoptin in the inhibition of liver cancer cells in vitro and analyzed the effect of inhibiting liver cancer in vivo by establishing a nude mouse tumor model. Flow cytometry and fluorescence staining were used to analyze the main types of apoptin-induced apoptosis and autophagy. Subsequently, the relationship between the two events was also analyzed. Flow cytometry was used to analyze the effect of ROS on apoptin-mediated apoptosis and autophagy mediated by apoptin. The effect of ROS on two phenomena was analyzed. Finally, the role of key genes involved in autophagy was analyzed using gene silencing. RESULTS: The results showed that apoptin can significantly increase the apoptosis and autophagy of liver cancer cells, and that apoptin can cause mitophagy through the increase in the expression of NIX protein. Apoptin can also significantly increase the level of cellular ROS, involved in apoptin-mediated autophagy and apoptosis of liver cancer cells. The change of ROS may be a key factor causing apoptosis and autophagy. CONCLUSION: The above results indicate that the increase in ROS levels after apoptin treatment of liver cancer cells leads to the loss of mitochondrial transmembrane potential, resulting in endogenous apoptosis and mitophagy through the recruitment of NIX. Therefore, ROS may be a key factor connecting endogenous apoptosis and autophagy induced by apoptin in liver cancer cells. Video abstract.

Ad-VT enhances the sensitivity of chemotherapy-resistant lung adenocarcinoma cells to gemcitabine and paclitaxel in vitro and in vivo.

Background One of the main challenges in the clinical treatment of lung cancer is resistance to chemotherapeutic drugs. P-glycoprotein (P-gp)-mediated drug resistance is the main obstacle to successfully implementing microtubule-targeted tumor chemotherapy. Purpose In this study, we explored the effect of Ad-hTERTp-E1a-Apoptin (Ad-VT) on drug-resistant cell lines and the molecular mechanism by which Ad-VT combined with chemotherapy affects drug-resistant cells and parental cells. Methods In vitro, cell proliferation, colony formation, resistance index (RI), apoptosis and autophagy assays were performed. Protein expression was analyzed by Western blotting. Finally, a xenograft tumor model in nude mice was used to detect tumor growth and evaluate histological characteristics. Results Our results showed that Ad-VT had an obvious killing effect on A549, A549/GEM and A549/Paclitaxel cancer cells, and the sensitivity of drug-resistant cell lines to Ad-VT was significantly higher than that of parental A549 cells. Compared with A549 cells, A549/GEM and A549/Paclitaxel cells had higher autophagy levels and higher viral replication ability. Ad-VT decreased the levels of p-PI3k, p-Akt and p-mTOR and the expression of P-gp. In vivo, Ad-VT combined with chemotherapy can effectively inhibit the growth of chemotherapy-resistant tumors and prolong the survival of mice. Conclusions Thus, the combination of Ad-VT and chemotherapeutic drugs will be a promising strategy to overcome chemoresistance.

Apoptin induces pyroptosis of colorectal cancer cells via the GSDME-dependent pathway.

Apoptin is a small molecular weight protein encoded by the VP3 gene of chicken anemia virus (CAV). It can induce apoptosis of tumor cells and play anti-tumorigenic functions. In this study, we identified a time-dependent inhibitory role of apoptin on the viability of HCT116 cells. We also demonstrated that apoptin induces pyroptosis through cleaved caspase 3, and with a concomitant cleavage of gasdermin E (GSDME) rather than GSDMD. GSDME knockdown switched the apoptin-induced cell death from pyroptosis to apoptosis in vitro. Furthermore, we demonstrated that the effect of apoptin on GSDME-dependent pyroptosis could be mitigated by caspase-3 and caspase-9 siRNA knockdown. Additionally, apoptin enhanced the intracellular reactive oxygen species (ROS), causing aggregation of the mitochondrial membrane protein Tom20. Moreover, bax and cytochrome c were released to the activating caspase-9, eventually triggering pyroptosis. Therefore, GSDME mediates the apoptin-induced pyroptosis through the mitochondrial apoptotic pathway. Finally, using nude mice xenografted with HCT116 cells, we found that apoptin induces pyroptosis and significantly inhibits tumor growth. Based on this mechanism, apoptin may provide a new strategy for colorectal cancer therapy.

Xuanbai Chengqi Decoction Ameliorates Pulmonary Inflammation via Reshaping Gut Microbiota and Rectifying Th17/Treg Imbalance in a Murine Model of Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic obstructive pulmonary disease (COPD), a prevalent obstructive airway disease, has become the third most common cause of death globally. Xuanbai Chengqi decoction (XBCQ) is a traditional Chinese medicine prescription for the acute exacerbation of COPD. Here, we aimed to reveal the therapeutic effects of XBCQ administration and its molecular mechanisms mediated by Th17/Treg balance and gut microbiota. METHODS: We determined the counts of Th17 and Treg cells in the serum of 15 COPD and 10 healthy subjects. Then, cigarette smoke extract-induced COPD mice were gavaged with low, middle, and high doses of XBCQ, respectively. Weight loss, pulmonary function and inflammation, Th17/Treg ratio, and gut microbiota were measured to evaluate the efficacy of XBCQ on COPD. RESULTS: COPD patients had a higher Th17/Treg ratio in the serum than healthy controls, which was consistent with the results in the lung and colon of COPD mice. The middle dose of XBCQ (M-XBCQ) significantly decreased the weight loss and improved the pulmonary function (FEV0.2/FVC) in COPD mice. Moreover, M-XBCQ alleviated lung inflammation by rectifying the Th17/Treg imbalance, reducing the expressions of TNF-α, IL-1ß, and MMP-9, and suppressing inflammatory cells infiltration. Meanwhile, M-XBCQ greatly improved the microbial homeostasis in COPD mice by accumulating probiotic Gordonibacter and Akkermansia but inhibiting the growth of pathogenic Streptococcus, which showed significant correlations with pulmonary injury. CONCLUSION: Oral M-XBCQ could alleviate COPD exacerbations by reshaping the gut microbiota and improving the Th17/Treg balance, which aids in elucidating the mechanism through which XBCQ as a therapy for COPD.

Staples versus sutures for skin closure in hip arthroplasty: a meta-analysis and systematic review.

OBJECTIVE: The purpose of the present study was to estimate complications and other outcomes associated with staple and suture closure after hip arthroplasty through meta-analysis techniques and a systematic review. METHODS: We searched for articles in EMBASE, PubMed, Medline, Web of Science and the Cochrane Library. To determine the eligibility of the searched trials, Cochrane Collaboration's Review Manager software was used to perform the meta-analysis. RESULTS: Five randomized controlled trials and one retrospective cohort trial were included in our study. Our study indicated that for skin closure after hip arthroplasty, the risks of superficial infection and prolonged discharge were higher with staples than with sutures. There was no significant difference between the two groups in terms of allergic reaction, dehiscence, inflammation, abscess formation, the Hollander Wound Evaluation Scale or patient's satisfaction with skin closure methods. However, suturing required a longer operating time. CONCLUSIONS: Closure with sutures is associated with lower risks of superficial infection and prolonged discharge than closure with staples following hip arthroplasty, but it may take more time.

The application of machine learning algorithms in predicting the length of stay following femoral neck fracture.

PURPOSE: Femoral neck fracture is a frequent cause of hospitalization, and length of stay is an important marker of hospital cost and quality of care provided. As an extension of traditional statistical methods, machine learning provides the possibility of accurately predicting the length of hospital stay. The aim of this paper is to retrospectively identify predictive factors of the length of hospital stay (LOS) and predict the postoperative LOS by using machine learning algorithms. METHOD: Based on the admission and perioperative data of the patients, linear regression was used to analyze the predictive factors of the LOS. Multiple machine learning models were developed, and the performance of different models was compared. RESULT: Stepwise linear regression showed that preoperative calcium level (P = 0.017) and preoperative lymphocyte percentage (P = 0.007), in addition to intraoperative bleeding (p = 0.041), glucose and sodium chloride infusion after surgery (P = 0.019), Charlson Comorbidity Index (p = 0.007) and BMI (P = 0.031), were significant predictors of LOS. The best performing model was the principal component regression (PCR) with an optimal MAE (1.525) and a proportion of prediction error within 3 days of 90.91%. CONCLUSION: Excessive intravenous glucose and sodium chloride infusion after surgery, preoperative hypocalcemia, preoperative high percentages of lymphocytes, excessive intraoperative bleeding, lower BMI and higher CCI scores were related to prolonged LOS by using linear regression. Machine learning could accurately predict the postoperative LOS. This information allows hospital administrators to plan reasonable resource allocation to fulfill demand, leading to direct care quality improvement and more reasonable use of scarce resources.

Effects of Apoptin-Induced Endoplasmic Reticulum Stress on Lipid Metabolism, Migration, and Invasion of HepG-2 Cells.

In this study, we investigated the effects of Apoptin-induced endoplasmic reticulum (ER) stress on lipid metabolism, migration and invasion of HepG-2 cells, and preliminarily explored the relationship between endoplasmic reticulum stress, lipid metabolism, migration, and invasion. The effects of Apoptin on ER function and structure in HepG-2 cells were determined by flow cytometry, fluorescence staining and western blotting by assessing the expression levels of ER stress related proteins. The effects of Apoptin on HepG-2 cells' lipid metabolism were determined by western blot analysis of the expression levels of triglyceride, cholesterol, and lipid metabolism related enzymes. The effects of Apoptin on HepG-2 cells' migration and invasion were studied using migration and invasion assays and by Western-blot analysis of the expression of proteins involved in migration and invasion. The in vivo effects of endoplasmic reticulum stress on lipid metabolism, migration and invasion of HepG-2 cells were also investigated by immunohistochemistry analysis of tumor tissues from HepG2 cells xenografted nude mice models. Both in vitro and in vivo experiments showed that Apoptin can cause a strong and lasting ER stress response, damage ER functional structure, significantly change the expression levels of lipid metabolism related enzymes and reduce the migration and invasion abilities of HepG-2 cells. Apoptin can also affect HepG-2 cells' lipid metabolism through endoplasmic reticulum stress and the abnormal expression of enzymes closely related to tumor migration and invasion. These results also showed that lipid metabolism may be one of the main inducements that reduce HepG-2 cells' migration and invasion abilities.