Suction versus non-suction drainage strategy after uniportal thoracoscopic lung surgery: a prospective cohort study.

Background: The postoperative outcomes of suction drainage versus non-suction drainage after uniportal video-assisted thoracoscopic surgery (UniVATS) come with little consensus. This study aimed to prospectively compare the postoperative outcomes of suction drainage versus non-suction drainage in patients who underwent UniVATS. Methods: Between October 2022 and January 2023, patients undergoing UniVATS were prospectively enrolled. The choice of drainage strategy (suction or non-suction) was at the surgeon's discretion. The primary outcome was chest tube duration, with secondary outcomes including postoperative drainage volume, pain scores, postoperative complications, length of hospital stay, and hospitalization cost. Baseline characteristics and postoperative outcomes were compared. Univariable and multivariable analyses were used to identify risk factors for postoperative outcomes. Results: A total of 206 patients were enrolled in this study, with 103 patients in each group. Baseline characteristics were well-balanced. The chest tube duration did not significantly differ between the two groups. However, suction drainage exhibited a significantly lower total drainage volume compared to non-suction drainage (280.00 vs. 400.00 mL, P=0.03). Suction drainage was associated with a significantly shorter postoperative hospital stay (3.00 vs. 4.00 days, P<0.001) and lower pain score on the second postoperative day (POD). Multivariable analyses also confirmed that suction drainage was significantly correlated with a lower total drainage volume and a shorter postoperative hospital stay. Conclusions: These findings suggested that the suction drainage was superior to non-suction drainage in terms of postoperative drainage volume and length of hospital stay in patients undergoing UniVATS.

A miRNA-7704/IL2RB/AKT feedback loop regulates tumorigenesis and chemoresistance in ovarian cancer.

Ovarian cancer is one of the most common gynecological tumors worldwide. Despite the availability of multiple treatments for ovarian cancer, its resistance to chemotherapy remains a significant challenge. miRNAs play crucial roles in the initiation and progression of cancer by affecting processes such as differentiation, proliferation, and chemoresistance. According to microarray and qPCR analyses, miR-7704 is significantly downregulated in cisplatin-resistant cells compared to parental cells. In this study, we found that miR-7704 inhibited the proliferation and promoted cisplatin sensitivity of ovarian cancer cells in vitro and in vivo. Moreover, ectopic expression of miR-7704 had the same effect as IL2RB knockdown. Further mechanistic studies revealed that miR-7704 played an inhibitory role by regulating IL2RB expression to inactivate the AKT signaling pathway. Furthermore, IL2RB reversed the miR-7704 mediated resistance to cisplatin in ovarian cancer. Based on these findings, miR-7704 and IL2RB show the potential as novel therapeutic targets for ovarian cancer.

[A survey on the application of convolutional neural networks in the diagnosis of occupational pneumoconiosis].

Pneumoconiosis ranks first among the newly-emerged occupational diseases reported annually in China, and imaging diagnosis is still one of the main clinical diagnostic methods. However, manual reading of films requires high level of doctors, and it is difficult to discriminate the staged diagnosis of pneumoconiosis imaging, and due to the influence of uneven distribution of medical resources and other factors, it is easy to lead to misdiagnosis and omission of diagnosis in primary healthcare institutions. Computer-aided diagnosis system can realize rapid screening of pneumoconiosis in order to assist clinicians in identification and diagnosis, and improve diagnostic efficacy. As an important branch of deep learning, convolutional neural network (CNN) is good at dealing with various visual tasks such as image segmentation, image classification, target detection and so on because of its characteristics of local association and weight sharing, and has been widely used in the field of computer-aided diagnosis of pneumoconiosis in recent years. This paper was categorized into three parts according to the main applications of CNNs (VGG, U-Net, ResNet, DenseNet, CheXNet, Inception-V3, and ShuffleNet) in the imaging diagnosis of pneumoconiosis, including CNNs in pneumoconiosis screening diagnosis, CNNs in staging diagnosis of pneumoconiosis, and CNNs in segmentation of pneumoconiosis foci to conduct a literature review. It aims to summarize the methods, advantages and disadvantages, and optimization ideas of CNN applied to the images of pneumoconiosis, and to provide a reference for the research direction of further development of computer-aided diagnosis of pneumoconiosis.

Mitochondrial dysfunction affects hepatic immune and metabolic remodeling in patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). However, the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear. AIM: To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders. METHODS: Liver samples were collected from 16 healthy donors (HDs) and 17 advanced HBV-ACLF patients who were eligible for liver transplantation. The mitochondrial ultrastructure, metabolic characteristics, and immune microenvironment of the liver were assessed. More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF. RESULTS: Compared with HDs, there was extensive hepatocyte necrosis, immune cell infiltration, and ductular reaction in patients with ACLF. In patients, the liver suffered severe hypoxia, as evidenced by increased expression of hypoxia-inducible factor-1α. Swollen mitochondria and cristae were observed in the liver of patients. The number, length, width, and area of mitochondria were adaptively increased in hepatocytes. Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased, while anaerobic glycolysis was enhanced in patients with HBV-ACLF. These findings suggested that, to a greater extent, hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source. Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate, which stimulates peripheral monocyte infiltration into the liver. Characterization and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68+ HLA-DR+ macrophages and elevated levels of both interleukin-1ß and transforming growth factor-ß1 in their livers. The abundance of CD206+ CD163+ macrophages and expression of interleukin-10 decreased. The correlation analysis revealed that hepatic organic acid metabolites were closely associated with macrophage-derived cytokines/chemokines. CONCLUSION: The results indicated that bioenergetic alteration driven by hypoxia and mitochondrial dysfunction affects hepatic immune and metabolic remodeling, leading to advanced HBV-ACLF. These findings highlight a new therapeutic target for improving the treatment of HBV-ACLF.

From hepatitis B virus infection to acute-on-chronic liver failure: The dynamic role of hepatic macrophages.

Acute-on-chronic liver failure (ACLF) is a progressive disease that is associated with rapid worsening of clinical symptoms and high mortality. A multicentre prospective study from China demonstrated that patients with hepatitis B virus-related ACLF (HBV-ACLF) exhibited worse clinical characteristics and higher mortality rates compared to non-HBV-ACLF patients. Immune dysregulation is closely linked to the potential mechanisms of initiation and progression of ACLF. Innate immune response, which is represented by monocytes/macrophages, is up-regulated across ACLF development. This suggests that monocytes/macrophages play an essential role in maintaining the immune homeostasis of ACLF. Information that has been published in recent years shows that the immune status and function of monocytes/macrophages vary in ACLF precipitated by different chronic liver diseases. Monocytes/macrophages have an immune activation effect in hepatitis B-precipitated-ACLF, but they exhibit an immune suppression in cirrhosis-precipitated-ACLF. Therefore, this review aims to explain whether this difference affects the clinical outcome in HBV-ACLF patients as well as the mechanisms involved. We summarize the novel findings that highlight the dynamic polarization phenotype and functional status of hepatic macrophages from the stage of HBV infection to ACLF development. Moreover, we discuss how different HBV-related liver disease tissue microenvironments affect the phenotype and function of hepatic macrophages. In summary, increasing developments in understanding the differences in immune phenotype and functional status of hepatic macrophages in ACLF patients will provide new perspectives towards the effective restoration of ACLF immune homeostasis.

Inhibition of Bromodomain Proteins Enhances Oncolytic HAdVC5 Replication and Efficacy in Pancreatic Ductal Adenocarcinoma (PDAC) Models.

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive type of pancreatic cancer, which rapidly develops resistance to the current standard of care. Several oncolytic Human AdenoViruses (HAdVs) have been reported to re-sensitize drug-resistant cancer cells and in combination with chemotherapeutics attenuate solid tumour growth. Obstacles preventing greater clinical success are rapid hepatic elimination and limited viral replication and spread within the tumour microenvironment. We hypothesised that higher intratumoural levels of the virus could be achieved by altering cellular epigenetic regulation. Here we report on the screening of an enriched epigenetics small molecule library and validation of six compounds that increased viral gene expression and replication. The greatest effects were observed with three epigenetic inhibitors targeting bromodomain (BRD)-containing proteins. Specifically, BRD4 inhibitors enhanced the efficacy of Ad5 wild type, Ad∆∆, and Ad-3∆-A20T in 3-dimensional co-culture models of PDAC and in vivo xenografts. RNAseq analysis demonstrated that the inhibitors increased viral E1A expression, altered expression of cell cycle regulators and inflammatory factors, and attenuated expression levels of tumour cell oncogenes such as c-Myc and Myb. The data suggest that the tumour-selective Ad∆∆ and Ad-3∆-A20T combined with epigenetic inhibitors is a novel strategy for the treatment of PDAC by eliminating both cancer and associated stromal cells to pave the way for immune cell access even after systemic delivery of the virus.

Preoperative H. pylori Eradication Therapy Facilitates Precise Delineation in Early Gastric Cancer with Current H. pylori Infection.

INTRODUCTION: Early gastric cancer with current Helicobacter pylori infection (HpC-EGC) is common, but it is still unclear whether H. pylori eradication therapy (Hp-ET) or endoscopic submucosal dissection (ESD) should be performed first. We evaluated Hp-ETs short-term effects on horizontal boundary delineations of HpC-EGC in ESD. METHODS: Prospectively enrolled HpC-EGC patients were randomly assigned to eradication or control groups. Operation scopes of HpC-EGC lesions were delineated with marking dots at 5 mm out of the endoscopic demarcation line by an independent endoscopist, unaware of eradication status, before formal circumferential incision. As representatives, precise delineation rate, the shortest distance of all marking dots to the pathological demarcation line in all slices of one intact resected specimen (Dmin), and negative marking dot specimen rate were examined. RESULTS: Twenty-three HpC-EGC patients (25 lesions) were allocated to eradication group and 26 patients (27 lesions) were allocated to the control group with similar eradication success rates and all were differentiated type. With improving background mucosa inflammation after Hp-ET and similar gastritis-like epithelium rates, 10 lesions (40.0%) in the eradication group were of precise delineation compared to control group with 2 lesions (7.4%) (relative risk = 5.40, 95% CI 1.31-22.28). Dmin of eradication and control groups were 4.17 ± 2.52 mm and 2.67 ± 2.30 mm (p = 0.029), accompanied by 4 (14.8%) and none (0.0%) specimens that exhibited positive marking dots (p = 0.11), respectively. CONCLUSION: For HpC-EGC patients, administrating eradication medication before ESD is beneficial for the precise delineation of lesions and reducing the risk of positive horizontal resection margins.

Effect of a prior thyroid cancer on the survival of lung cancer patients: a retrospective study based on SEER database.

PURPOSE: The effect of a history of thyroid cancer on the prognosis of lung cancer patients has not been fully investigated. Therefore, we aimed to evaluate this effect based on a large cohort. METHODS: Data of 154844 lung cancer patients, of whom 406 had prior thyroid cancer, were collected from SEER database. Primary survival analysis was conducted between patients with and without prior thyroid cancer using Kaplan-Meier method. Secondary survival analysis was conducted to investigate the effects of the stage and histological subtype of the prior thyroid cancer on the survival of lung cancer patients. Propensity adjustment was used to reduce confounding effect. RESULTS: Compared to patients without prior malignancy, patients with prior thyroid cancer were predominantly female (72.4% vs. 48.7%, p < 0.001), had lower stage (proportion of localized tumor: 40.4% vs. 25.6%, p < 0.001), and larger proportion of surgery (52.2% vs. 29.4%, p < 0.001), and had better survival (5-year survival rate: 55.53% vs. 33.16%, p < 0.001). After propensity adjustment, the survival was similar between the groups (5-year survival rate: 55.53% vs. 51.78%, p = 0.24). The survival of patients with different stages (localized tumor vs. regional tumor: p = 0.88) or different histological subtypes (p = 0.46) of prior thyroid cancer were comparable. CONCLUSION: Survival of lung cancer patients with or without prior thyroid cancer was similar after propensity adjustment, and the stage or histological subtype of the prior thyroid cancer had no significant effect on the survival of lung cancer patients.

Free water alterations in different inflammatory subgroups in schizophrenia.

BACKGROUND: Accumulating evidence suggests that inflammatory dysregulation both in blood and the brain is implicated in the pathogenesis of schizophrenia. Alterations in peripheral cytokines are not evident in all patients and there may be discrete altered inflammatory subgroups in schizophrenia. Recent studies using a novel and in vivo free-water imaging to detect inflammatory processes, have shown increased free water in white matter in schizophrenia. However, no studies to date have investigated the free water alterations in different inflammatory subgroups in schizophrenia. METHODS: Forty-four patients with schizophrenia and 49 controls were recruited. The serum levels of interleukin-1 beta (IL-1ß), IL-6, IL-10, and IL-12p70 were measured and used for cluster analysis with K-means and hierarchical algorithms. Diffusion tensor imaging (DTI) images were collected for all participants and voxel-wise free water and fractional anisotropy of tissue (FA-t) were compared between groups with Randomise running in FSL. Partial correlation analysis was employed to explore the association of the peripheral cytokine levels with free water. RESULTS: We identified two statistically quantifiable discrete subgroups of patients based on the cluster analysis of cytokine measures. The peripheral levels of IL-1ß (P < 0.001), IL-10 (P = 0.041), and IL-12p70 (P < 0.001) showed significant differences between the two different inflammatory subgroups. In the inflammatory subgroup with a predominantly higher IL-1ß level, increased free water values in white matter were found mainly in the left posterior limb of the internal capsule, posterior corona radiata, and partly in the left sagittal stratum. These affected areas did not overlap with the regions that showed significant free water differences between patients and healthy controls. In the inflammatory subgroup with lower IL-1ß levels, peripheral IL-1ß was significantly associated with free water values in white matter while no such association was detected in the patient group. CONCLUSIONS: Localized free water differences were demonstrated between the two identified inflammatory subgroups in our data, and free water appears to be a feasible in vivo neuroimaging biomarker guiding the target of inflammatory intervention and development of new therapeutic strategies in an individualized manner in schizophrenia.

Shaoyao decoction alleviates TNBS-induced ulcerative colitis by decreasing inflammation and balancing the homeostasis of Th17/Treg cells.

BACKGROUND: Ulcerative colitis (UC) is a persistent and non-specific inflammatory condition that mainly affects the bowels and has challenging treatment. UC has a growing incidence and significantly affects the well-being of patients. Many medications used to treat UC can disrupt the metabolism and immune system homeostasis, frequently leading to significant adverse effects. Hence, exploring alternative therapies, such as traditional Chinese medicine and probiotics, has recently emerged as a primary research hotspot owing to their safety. Although the therapeutic mechanism of Shaoyao decoction has not been clarified, it has demonstrated a beneficial clinical effect on UC. AIM: This study aimed to assess the effect of Shaoyao decoction on a rat model of UC and investigate its underlying mechanisms. METHODS: The rat model of UC was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). The extent of damage to the intestines was assessed using the disease activity index (DAI), colonic mucosa damage index (CMDI), and histological scores. Immunohistochemistry was employed to detect the tissue levels of interleukin (IL)-17, transforming growth factor (TGF)-ß1, and IL-10. Additionally, the proportion of Th17 and Treg cells was detected using flow cytometry. In colon tissue, the levels of forkhead box (Fox)p3, RAR-related orphan receptor (ROR)γt, IL-6, p-STAT3, and STAT3 proteins were quantified by Western blotting. RESULTS: Treatment with Shaoyao decoction enhanced the overall health of rats and reduced colonic damage. Additionally, Shaoyao decoction significantly alleviated the severity of DAI, CMDI, and HS. The proportion of Th17 cells was reduced, and the proportion of Treg cells was increased by Shaoyao decoction. The expression of IL-17 and RORγt was suppressed by Shaoyao decoction, while the expression of IL-10, TGF-ß1, and Foxp3 was increased. The expression of IL-6, p-STAT3, and STAT3 was decreased by Shaoyao decoction. CONCLUSION: The Shaoyao decoction alleviates the symptoms of TNBS-induced UC by decreasing inflammation and mitigating intestinal damage while preserving the balance between Th17 and Treg. Shaoyao decoction modulates the IL-6/STAT3 axis, thereby regulating the balance between Th17 and Treg cells.

Genetically predicted childhood body mass index and lung cancer susceptibility: A two-sample Mendelian randomization study.

BACKGROUND: The association between adult body mass index (BMI) and lung cancer (LC) susceptibility have been reported, but the causal relationship with childhood BMI remains largely unclear. To evaluate the causal effect of childhood BMI on LC susceptibility, a two-sample Mendelian randomization (MR) study was performed. METHODS: The two-sample MR analysis utilized 25 single nucleotide polymorphisms (SNPs) as instrumental variables for childhood BMI. Genetic summary data from the International Lung Cancer Consortium and FinnGen databases were analyzed to estimate the causal effect of these SNPs on LC susceptibility. The IVW method was employed as the primary analysis, supplemented by the Weighted Median, MR-Egger, and MR pleiotropy residual sum and outlier test. RESULTS: Our findings indicated that there was no causal association between childhood BMI and the susceptibility of LC (odds ratio [OR]: 1.03, 95% confidence interval [CI]: 0.90-1.17, p = 0.705), lung adenocarcinoma (OR: 0.99, 95% CI: 0.86-1.13, p = 0.832), lung squamous cell carcinoma (OR: 0.97, 95% CI: 0.84-1.13, p = 0.726), and small cell LC (OR: 1.09, 95% CI: 0.82-1.45, p = 0.554) based on the IVW as well as other methods employed. Furthermore, these findings indicated no causal effect of childhood BMI on the LC susceptibility in both ever smokers and never smokers. CONCLUSION: This study did not conclude a causal effect between childhood BMI and LC susceptibility. However, given the complex nature of cancer development, further studies are needed to verify these findings.

Risk-based screening for second primary extrapulmonary malignancies in stage I lung cancer patients: A study based on SEER database.

OBJECTIVES: We conducted this study to identify the risk for second primary malignancy (SPM), especially for second primary extrapulmonary malignancy (SPEM), in resected stage I lung cancer patients. MATERIALS AND METHODS: Resected stage I lung cancer patients were retrospectively enrolled from the SEER database (2008-2017). Standardized incidence ratio (SIR) was used to evaluate the relative risk of SPM of patients as compared to general population. Competing risk model was utilized to identify the risk factors for SPEM of increased risk (rSPEM). A simplified nomogram based on the factors was developed to stratify patients at different risks of rSPEM. RESULTS: A total of 14,495 patients were enrolled, and 1779 (12.27%) patients developed SPM during follow-up, of which 896 (50.37%) were SPEM. Enrolled patients had higher risk of SPM than general population (SIR: 1.92, 95% CI: 1.83 - 2.01). The yearly morbidity of SPM was about 3% - 4% over time. The three most frequent SPEM were prostate cancer, breast cancer, and urinary bladder cancer. The competing-risk multivariable analysis showed that increasing age, male, and white race were independent risk factors for rSPEM. The simplified nomogram showed favorable performance in stratifying patients at different risks of rSPEM (P < 0.001). CONCLUSION: The risk of SPM in stage I lung cancer patients was high. Risk factors for rSPEM were identified and the corresponding simplified nomogram based on the risk factors could discriminate patients at different risks well. The nomogram might help physicians to make more appropriate screening strategy for the SPEM.

Endoscopic ultrasound-guided tissue acquisition with or without rapid on-site evaluation for solid pancreatic lesions: five years of experience from a single center.

BACKGROUND: Endoscopic ultrasound (EUS)-guided tissue acquisition (TA) by EUS-guided fine needle aspiration (FNA) or fine needle biopsy (FNB) is a standard diagnostic procedure for solid pancreatic lesions. Whether rapid on-site evaluation (ROSE) should be used to support EUS-TA remains controversial. Here we assessed the diagnostic performance of EUS-TA with or without self-ROSE for solid pancreatic masses. METHODS: Three hundred and seventy EUS-TA cases with self-ROSE and 244 cases without ROSE were retrospectively enrolled between August 2018 and June 2022. All procedures including ROSE were performed by the attending endoscopist. Clinical data, EUS characteristics, and diagnostic performance for distinguishing benign from malignant solid pancreatic masses including accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared between groups. RESULTS: Self-ROSE improved the diagnostic accuracy of solid pancreatic lesions by 16.7% in the EUS-TA group (p < 0.001) and by 18.9% in the EUS-FNA alone group (p < 0.001). Self-ROSE also improved the diagnostic sensitivity by 18.6% in the EUS-TA group (p < 0.001) and by 21.2% in the EUS-FNA alone group (p < 0.001). Improvements in the diagnostic accuracy by self-ROSE in the EUS-FNB group were not significant. 2.2 ± 0.7, 2.4 ± 0.9, 2.3 ± 0.7, 2.5 ± 0.9, 2.1 ± 0.6, and 2.1 ± 0.7 needle passes were required in the EUS-TA, EUS-FNA, and EUS-FNB with or without self-ROSE groups, respectively. CONCLUSIONS: Self-ROSE significantly improved the accuracy and sensitivity of EUS-FNA alone and EUS-TA diagnosis of solid pancreatic lesions and helped to reduce needle passes during the procedure. Whether self-ROSE benefits EUS-FNB and whether EUS-FNB alone is comparable to EUS-FNA with self-ROSE require further clarification.

A Competing Risk Model Nomogram to Predict the Long-Term Prognosis of Lung Carcinoid.

BACKGROUND: The prediction of long-term, cancer-specific survival of lung carcinoid remains controversial. We aimed to build a prognostic model by using competing-risk analysis to predict the long-term, cancer-specific survival of lung carcinoid patients. METHODS: Patients were retrospectively enrolled from the SEER database, and clinicopathological data were collected. Univariable and multivariable competing-risk analyses were conducted to identify prognostic factors. A competing-risk model and a nomogram were developed by using independent prognostic factors. The model was assessed by using concordance index and calibration curves. RESULTS: A total of 2496 patients were enrolled, of which 267 (10.7%) died of diagnosed carcinoma; 316 (12.7%) died because of other reasons. The 5-year, 10-year, and 15-year cancer-specific survival of carcinoid patients were 91.35%, 86.60%, and 84.39%, respectively. Multivariable analysis demonstrated that increasing age, male, larger tumor size, higher N stage, M1, atypical carcinoid, and undergoing no surgery were independent risk factors. A competing-risk model based on the risk factors and a corresponding nomogram were developed. Concordance index of the developed model for 5-year, 10-year, and 15-year were 0.891, 0.856, 0.836 respectively in the training cohort and 0.876, 0.841, 0.819 respectively in the validation cohort after bootstrap adjustment. The calibration curves of 5-year, 10-year, and 15-year showed good agreement. CONCLUSIONS: Increasing age, male, larger tumor size, higher N stage, M1, atypical carcinoid, and undergoing no surgery were independent risk factors. A competing risk model of excellent performance in predicting long-term survival was developed, and a nomogram was established.

Roles of alternative splicing in infectious diseases: from hosts, pathogens to their interactions.

ABSTRACT: Alternative splicing (AS) is an evolutionarily conserved mechanism that removes introns and ligates exons to generate mature messenger RNAs (mRNAs), extremely improving the richness of transcriptome and proteome. Both mammal hosts and pathogens require AS to maintain their life activities, and inherent physiological heterogeneity between mammals and pathogens makes them adopt different ways to perform AS. Mammals and fungi conduct a two-step transesterification reaction by spliceosomes to splice each individual mRNA (named cis -splicing). Parasites also use spliceosomes to splice, but this splicing can occur among different mRNAs (named trans -splicing). Bacteria and viruses directly hijack the host's splicing machinery to accomplish this process. Infection-related changes are reflected in the spliceosome behaviors and the characteristics of various splicing regulators (abundance, modification, distribution, movement speed, and conformation), which further radiate to alterations in the global splicing profiles. Genes with splicing changes are enriched in immune-, growth-, or metabolism-related pathways, highlighting approaches through which hosts crosstalk with pathogens. Based on these infection-specific regulators or AS events, several targeted agents have been developed to fight against pathogens. Here, we summarized recent findings in the field of infection-related splicing, including splicing mechanisms of pathogens and hosts, splicing regulation and aberrant AS events, as well as emerging targeted drugs. We aimed to systemically decode host-pathogen interactions from a perspective of splicing. We further discussed the current strategies of drug development, detection methods, analysis algorithms, and database construction, facilitating the annotation of infection-related splicing and the integration of AS with disease phenotype.

The Duck RXRA Gene Promotes Adipogenesis and Correlates with Feed Efficiency.

BACKGROUND: The accumulation of fat in ducks is the main cause of low feed efficiency and metabolic diseases in ducks. Retinoic acid X receptor alpha (RXRA) is a member of the nuclear receptor superfamily involved in lipid, glucose, energy, and hormone metabolism. The effect of the RXRA gene on lipid metabolism in duck preadipocytes (DPACs) and the relationship between SNPs and the feed efficiency traits of ducks are unclear. METHODS: qRT-PCR and Western blotting analyses were used to detect changes in mRNA and protein in cells. Intracellular triglycerides (TGs) were detected using an ELISA kit. A general linear model analysis was used to determine the association between RXRA SNPs and feed efficiency. RESULTS: The duck RXRA gene was highly expressed on the fourth day of DPAC differentiation. The RXRA gene increased the content of fat and TG in DPACs and promoted the expression of cell differentiation genes; g.5,952,667 correlated with average daily feed intake (ADFI), residual feed intake (RFI), and feed conversion ratio (FCR). CONCLUSIONS: Duck RXRA can accelerate fat accumulation, and the polymorphism of the RXRA gene is closely related to feed efficiency, which provides basic data for breeding high feed efficiency ducks.

A Novel in Duck Myoblasts: The Transcription Factor Retinoid X Receptor Alpha (RXRA) Inhibits Lipid Accumulation by Promoting CD36 Expression.

Retinoid X receptor alpha (RXRA) is a well-characterized factor that regulates lipid metabolism; however, the regulatory mechanism in muscle cells of poultry is still unknown. The overexpression and the knockdown of RXRA in myoblasts (CS2 cells), RT-PCR, and western blotting were used to detect the expression levels of genes and proteins related to PPAR-signaling pathways. Intracellular triglycerides (TGs), cholesterol (CHOL), and nonesterified free fatty acids (NEFAs) were detected by the Elisa kit. Fat droplets were stained with Oil Red O. The double-fluorescein reporter gene and chromatin immunoprecipitation (CHIP) were used to verify the relationship between RXRA and candidate target genes. The RXRA gene was highly expressed in duck breast muscle, and its mRNA and its protein were reduced during the differentiation of CS2 cells. The CS2 cells, with the overexpression of RXRA, showed reduced content in TGs, CHOL, NEFAs, and lipid droplets and upregulated the mRNA expression of CD36, ACSL1, and PPARG genes and the protein expression of CD36 and PPARG. The knockdown of RXRA expression in CS2 cells enhanced the content of TGs, CHOL, NEFAs, and lipid droplets and downregulated the mRNA and protein expression of CD36, ACLS1, ELOVL6, and PPARG. The overexpression of the RXRA gene, the activity of the double-luciferase reporter gene of the wild-type CD36 promoter was higher than that of the mutant type. RXRA bound to -860/-852 nt, -688/-680 nt, and -165/-157 nt at the promoter region of CD36. Moreover, the overexpression of CD36 in CS2 cells could suppress the content of TGs, CHOL, NEFAs, and lipid droplets, while the knockdown expression of CD36 increased the content of TGs, CHOL, NEFAs, and lipid droplets. In this study, the transcription factor, RXRA, inhibited the accumulation of TGs, CHOL, NEFAs, and fat droplets in CS2 cells by promoting CD36 expression.

A Clinical Prediction Model for Postoperative Pneumonia After Lung Cancer Surgery.

INTRODUCTION: Postoperative pneumonia (POP) is a common complication following lung cancer surgery and is associated with increased hospitalization costs and mortalities. We aimed to identify risk factors associated with POP and to develop a reliable predictive model. METHODS: Patients who underwent lung cancer surgery between January 2015 and December 2021 in our hospital were enrolled. Least absolute shrinkage and selection operator regression analysis was used to select predictors of POP. Multivariable logistic regression was performed to construct the nomogram. Bootstrap resampling was conducted for internal validation. The performance of the model was evaluated by discrimination and calibration. RESULTS: A total of 5269 consecutive patients were enrolled. POP occurred in 1.7% of patients (92/5269). Five independent predictors were identified: age, predicted forced expiratory volume in 1 s, predicted diffusing capacity of the lungs for carbon monoxide, tuberculosis history, and surgery duration. The multivariable regression model showed good discrimination (C-index: 0.821, 95% confidence interval, 0.783-0.859), which was well validated by internal validation. The calibration curve illustrated good agreement between the predicted probability and observed probability of POP. CONCLUSIONS: Based on the easily available risk factors, our nomogram could predict the risk of POP with good discrimination and calibration. The model has good clinical practicability, enabling precise and targeted interventions to reduce the incidence of POP in high-risk patients.