Predicting lung cancer survival prognosis based on the conditional survival bayesian network.

Lung cancer is a leading cause of cancer deaths and imposes an enormous economic burden on patients. It is important to develop an accurate risk assessment model to determine the appropriate treatment for patients after an initial lung cancer diagnosis. The Cox proportional hazards model is mainly employed in survival analysis. However, real-world medical data are usually incomplete, posing a great challenge to the application of this model. Commonly used imputation methods cannot achieve sufficient accuracy when data are missing, so we investigated novel methods for the development of clinical prediction models. In this article, we present a novel model for survival prediction in missing scenarios. We collected data from 5,240 patients diagnosed with lung cancer at the Weihai Municipal Hospital, China. Then, we applied a joint model that combined a BN and a Cox model to predict mortality risk in individual patients with lung cancer. The established prognostic model achieved good predictive performance in discrimination and calibration. We showed that combining the BN with the Cox proportional hazards model is highly beneficial and provides a more efficient tool for risk prediction.

Bidirectional crosstalk of the cAMP/ROS-dependent signaling pathways in inflammatory macrophage: An activation of formononetin.

Bacterial lipopolysaccharide (LPS) is a toxic stimulant to macrophage inflammation. Inflammation intersects cell metabolism and often directs host immunopathogenesis stress. We aim here at pharmacological discovering of formononetin (FMN) action, to which anti-inflammatory signaling spans across immune membrane receptors and second messenger metabolites. In ANA-1 macrophage stimulated by LPS, and simultaneous treatment with FMN, results show the Toll-like receptor 4 (TLR4) and estrogen receptor (ER) signals, in concert with reactive oxygen species (ROS) and cyclic adenosine monophosphate (cAMP), respectively. LPS stimulates inactivation of the ROS-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) by upregulating TLR4, but it does not affect cAMP. However, FMN treatment not only activates Nrf2 signaling by TLR4 inhibition, but also it activates cAMP-dependent protein kinase activities by upregulating ER. The cAMP activity gives rise to phosphorylation (p-) of protein kinase A, liver kinase B1 and 5'-AMP activated protein kinase (AMPK). Moreover, bidirectional signal crosstalk is amplified between p-AMPK and ROS, as FMN combinational validation with AMPK activator/inhibitor/target small-interfering RNA or ROS scavenger. The signal crosstalk is well positioned serving as the 'plug-in' knot for rather long signaling axis, and the immune-to-metabolic circuit via ER/TLR4 signal transduction. Collectively, convergence of the FMN-activated signals drives significant reduction of cyclooxygenase-2, interleukin-6 and NLR family pyrin domain-containing protein 3, in LPS-stimulated cell. Although anti-inflammatory signaling is specifically related to the immune-type macrophage, the p-AMPK antagonizing effect arises from FMN combination with ROS scavenger H-bond donors. Information of our work assists in predictive traits against macrophage inflammatory challenges, using phytoestrogen discoveries.

Prevalence and risk factors of ischemic stroke-related headache in China: a systematic review and meta-analysis.

BACKGROUND: Headache accompanying ischemic stroke is considered an independent predictor of neurological deterioration. This meta-analysis aims to estimate the prevalence of ischemic stroke-related headaches and identify its risk factors in China. METHODS: PubMed, Embase, Cochrane Library database, Web of Science, PsycINFO, and four Chinese databases for the related publications were searched. Two researchers independently selected the literature, extracted the relevant data, and assessed its methodological quality. The meta-analysis applied a random-effects model with R software to calculate the pooled prevalence of ischemic stroke-related headaches in Chinese patients, and to merge the odds ratio (OR) of risk factors. Subgroup analysis, sensitivity analysis, and meta-regression analysis were conducted. Publication bias was assessed by a funnel plot and Egger test. RESULTS: Ninety-eight studies were eligible for inclusion. The overall pooled prevalence of ischemic stroke-related headache was 18.9%. Subgroup analysis showed that the prevalence of ischemic stroke related-headaches was higher among studies using self-report to diagnosis headache (18.9%; 95%CI, 8.9% to 40.2%), and those focused on age ≥ 55 years (19.7%; 95%CI, 14.9% to 25.9%), rural settings (24.9%; 95%CI, 19.7% to 31.6%). There were no significant differences in the headache prevalence between studies in the south and north, and inland and coastal studies. The prevalence of pre onset headache (13.9%) and tension-type headache (15.5%) and was higher compared with other types. History of headache (OR = 3.24; 95%CI, 2.26 to 4.65.), female gender (OR = 2.06; 95%CI, 1.44 to 2.96.), midbrain lesions (OR = 3.56; 95%CI, 1.86 to 6.83.), and posterior circulation stroke (OR = 2.13; 95%CI, 1.14 to 4.32) were major risk factors. CONCLUSION: The prevalence of ischemic stroke-associated headache is high in China. In addition, women, presence of midbrain lesions, posterior circulation stroke and a history of migraine were high-risk factors for ischemic stroke-related headaches. Designing effective interventions to prevent or alleviated headaches is necessary to promote patients' neurological recovery and quality of life.

Nanoemulsion Co-Loaded with XIAP siRNA and Gambogic Acid for Inhalation Therapy of Lung Cancer.

Lung cancer is a leading cause of cancer mortality worldwide, with a 5-year survival rate of less than 20%. Gambogic acid (GA) is a naturally occurring and potent anticancer agent that destroys tumor cells through multiple mechanisms. According to the literature, one of the most potent inhibitors of caspases and apoptosis currently known is the X-linked Inhibitor of Apoptosis Protein (XIAP). It is highly expressed in various malignancies but has little or no expression in normal cells, making it an attractive target for cancer treatment. Here we report the development of a chitosan (CS)-based cationic nanoemulsion-based pulmonary delivery (p.d.) system for the co-delivery of antineoplastic drugs (GA) and anti-XIAP small interfering RNA (siRNA). The results showed that the chitosan-modified cationic nanoemulsions could effectively encapsulate gambogic acid as well as protect siRNA against degradation. The apoptosis analysis confirmed that the cationic nanoemulsions could induce more apoptosis in the A549 cell line. In addition, most drugs and siRNAs have a long residence time in the lungs through pulmonary delivery and show greater therapeutic effects compared to systemic administration. In summary, this work demonstrates the applicability of cationic nanoemulsions for combined cancer therapy and as a promising approach for the treatment of lung cancer.

Down-regulation of miR-30b-5p protects cardiomyocytes against hypoxia-induced injury by targeting Aven.

BACKGROUND: Ischemia/hypoxia-induced cardiomyocyte apoptosis has been considered as a main cause of myocardial infarction. Here, we aimed to investigate the functional role of miR-30b-5p in hypoxic cardiomyocytes. METHODS: AC16 human cardiomyocytes were cultured under hypoxia to simulate myocardial infarction. A qRT-PCR assay was performed to determine miR-30b-5p expression in hypoxic cardiomyocytes. Cell survival, injury and apoptosis were assessed by MTT, lactate dehydrogenase (LDH) release, and flow cytometry assays, respectively. The target gene of miR-30b-5p in hypoxic cardiomyocytes was validated by luciferase reporter assay and Western blotting. RESULTS: MiR-30b-5p expression was found to be significantly upregulated in hypoxic AC16 cells. The in vitro experiments showed that downregulation of miR-30b-5p effectively alleviated hypoxia-induced cardiomyocyte injury. Furthermore, Aven is a potential target gene of miR-30b-5p and its downregulation could partially reverse the influence of miR-30b-5p knockdown on AC16 cells under hypoxia. CONCLUSIONS: Inhibition of miR-30b-5p could protect cardiomyocytes against hypoxia-induced injury by targeting Aven.

Association of blood eosinophilia and vitamin D insufficiency in young infants with cow milk allergy.

BACKGROUND AND OBJECTIVES: Cow milk allergy is the most common food allergic disease in young infants and vitamin D has a critical role in regulating intestinal inflammation. METHODS AND STUDY DESIGN: To determine roles of vitamin D in cow milk allergy, fifty-six young infants with cow milk allergy were enrolled. The serum 25-hydroxyvitamin D (25OHD), total and specific IgE, circulating regulatory T lymphocytes, and blood eosino-phil counts were determined. RESULTS: The serum 25OHD in cow milk allergy and age-matched infants were sim-ilar (68.3±38.9 nmol/L versus 72.9±33.1 nmol/L, p>0.05), 71% Cow milk allergy infants (40/56) had serum 25OHD lower than 75 nmol/L compared to 66% (37/56) in the controls. The cow milk allergy infants with 25OHD lower than 75 nmol/L had persistent blood eosinophilia and delayed resolution of symptoms after cow milk elimination compared to those with 25OHD above 75 nmol/L (odd ratio 3.7, 95% CI 1.1-12.6, p<0.05). The serum 25OHD inversely correlated with blood eosinophil counts after cow milk elimination (r=-0.37, p<0.01). Cow milk allergy infants with 25OHD lower than 50 nmol/L (vitamin D deficiency, n = 22) were in general at younger age (1.6±0.6 months) compared to infants with insufficient (50-75 nmol/L) or normal (>=75 nmol/L) group (4.3±1.2 and 4.6±0.9 months, respectively, p<0.001). CONCLUSIONS: Low serum vitamin D associates with persistent blood eosinophilia and symptoms in young cow milk allergy infants.

SLC34A2 regulates miR-25-Gsk3ß signaling pathway to affect tumor progression in gastric cancer stem cell-like cells.

A novel paradigm in tumor biology suggests that gastric cancer progression is driven by gastric cancer stem cell-like cells (GCSCs), but molecular mechanisms regulating tumorigenic and self-renewal potential of GCSCs are still unclear. Here, we aim to investigate biological function of SLC34A2 in regulating sphere formation and tumorigenicity (both are the hallmark of CSCs) of GCSCs and its underlying mechanisms. Our findings testified that CD44+ cells which were derived from fresh primary gastric cancer samples and cell lines displayed stem cell-like features. Significantly, SLC34A2 is increased in CD44+ GCSCs compared with those in adherent counterpart from CD44+ GCSCs. On clinic, SLC34A2 is overexpressed in primary tumor tissues compared with adjacent counterparts. We showed that SLC34A2 regulated sphere formation and self-renewal properties of CD44+ GCSCs in vitro and in vivo. Mechanistic investigations revealed that Gsk3ß was the most strikingly up-regulated gene in response to SLC34A2 knockdown in GCSCs and Wnt/ß-cantenin signaling was required for SLC34A2-mediated sphere formation. Furthermore, SLC34A2 directly binds specific sites in the miR-25 promoter region and that the promoter activity is decreased after the mutation of putative SLC34A2-binding sites, indicating that SLC34A2 is required for the transcriptional induction of miR-25. Meanwhile, luciferase assays showed that miR-25 directly targeted Gsk3ß in CD44+ GCSCs. Overall, our findings define a SLC34A2-miR-25-Gsk3ß pathway in the regulation of GCSCs features and gastric cancer progression, with potential therapeutic applications in blocking their progression.

Systematic analysis of genes involved in oral cancer metastasis to lymph nodes.

Oral cancer remains a deadly disease worldwide. Lymph node metastasis and invasion is one of the causes of death from oral cancer. Elucidating the mechanism of oral cancer lymph node metastasis and identifying critical regulatory genes are important for the treatment of this disease. This study aimed to identify differentially expressed genes (gene signature) and pathways that contribute to oral cancer metastasis to lymph nodes. The GSE70604-associated study compared gene profiles in lymph nodes with metastasis of oral cancer to those of normal lymph nodes. The GSE2280-associated study compared gene profiles in primary tumor of oral cancer with lymph node metastasis to those in tumors without lymph node metastasis. There are 28 common differentially expressed genes (DEGs) showing consistent changes in both datasets in overlapping analysis. GO biological process and KEGG pathway analysis of these 28 DEGs identified the gene signature CCND1, JUN and SPP1, which are categorized as key regulatory genes involved in the focal adhesion pathway. Silencing expression of CCND1, JUN and SPP1 in the human oral cancer cell line OECM-1 confirmed that those genes play essential roles in oral cancer cell invasion. Analysis of clinical samples of oral cancer found a strong correlation of these genes with short survival, especially JUN expression associated with metastasis. Our study identified a unique gene signature - CCND1, JUN and SPP1 - which may be involved in oral cancer lymph node metastasis.

Effect of Different Methods of Administration of Diltiazem on Clinical Efficacy in Patients with Acute ST-Segment Elevation Myocardial Infarction.

BACKGROUND The aim of this study was to investigate the optimal route of administration of diltiazem in emergency PCI and to provide the best clinical treatment for ASTEMI patients. MATERIAL AND METHODS A total of 90 patients with ASTEMI treated in our hospital from January 2015 to January 2016 were selected. Prior to thrombus aspiration, a thrombus aspiration catheter was used to perform diltiazem injection at the distal end of the infarct-related artery (IRA). We chose the acute ST-elevation myocardial infarction (ASTEMI) patients treated with direct PCI to compare different administration routes of diltiazem. The occurrence of major adverse cardiac events (MACEs) was closely observed during hospitalization and was obtained through outpatient visits or telephone follow-ups over the next 6 months. RESULTS Intracoronary infusion of diltiazem at the distal end of the culprit vessel, compared to conventional coronary mouth and intravenous injection, was significantly improved in thrombolysis in myocardial infarction (TIMI) frame count immediately after PCI stent implantation, ST-segment drop rate after 90 min, and left ventricular ejection fraction (LVEF) after 1 week. Furthermore, the peak value of high-sensitivity cardiac troponin I (hs-cTnI), a marker for myocardial injury, was the lowest. White blood cell count, neutrophil count, mean platelet volume (MPV), and high-sensitivity C-reactive protein (hs-CRP) were significantly lower than with the other 2 administration routes, and there was no effect on intracoronary pressure or heart rate. CONCLUSIONS Patients with ASTEMI who underwent emergency PCI treatment had good clinical outcomes using intracoronary diltiazem at the distal end of the culprit vessel.

Upregulated miR-132 in Lgr5+ gastric cancer stem cell-like cells contributes to cisplatin-resistance via SIRT1/CREB/ABCG2 signaling pathway.

Cisplatin resistance has long been a major problem that restricts its use. A novel paradigm in tumor biology suggests that gastric tumor chemo-resistance is driven by gastric cancer stem cell-like (GCSCs). Growing evidence has indicated that microRNAs (miRNAs) contributes to chemo-resistance in gastric cancer (GC). Here, Lgr5+ cells derived from gastric cancer cell lines displayed stem cell-like features. Flow cytometry demonstrated the presence of a variable fraction of Lgr5 in 19 out of 20 GC specimens. By comparing the miRNA expression profiles of Lgr5+ GCSCs and Lrg5- cells, we established the upregulation of miR-132 in Lgr5+ GCSCs. The enhanced miR-132 expression correlated chemo-resistance in GC patients. Kaplan-Meier survival curve showed that patients with low miR-132 expression survived obviously longer. Functional assays results indicated that miR-132 promoted cisplatin resistance in Lgr5+ GCSCs in vitro and in vivo. Further dual-luciferase reporter gene assays revealed that SIRT1 was the direct target of miR-132. The expression of miR-132 was inversely correlated with SIRT1 in gastric cancer specimens. Furthermore, through PCR array we discovered ABCG2 was one of the downstream targets of SIRT1. Overexpression of SIRT1 down-regulated ABCG2 expression by promoting the de-acetylation of the transcription factor CREB. CREB was further activated ABCG2 via binding to the promoter of ABCG2 to induce transcription. Thus, we concluded that miR-132 regulated SIRT1/CREB/ABCG2 signaling pathway contributing to the cisplatin resistance and might serve as a novel therapeutic target against gastric cancer.

Imbalance of peripheral blood Th17 and Treg responses in children with refractory Mycoplasma pneumoniae pneumonia.

Mycoplasma pneumoniae (MP) pneumonia is usually a benign self-limiting disease, but some patients suffer from acute lung injury in MP infections who need to use immune-modulators with conventional antibiotic treatment. The imbalance between CD4+CD25+Foxp3+regulatory T (Treg) cells and T helper (Th17) cells has been found in a number of different inflammation and autoimmune disease, while the role of the Th17/Treg balance in MP pneumonia remains largely unknown. The aim of this study was to investigate the Th17/Treg pattern and its impact on disease severity in patients with MP pneumonia. This study involved 36 healthy control and 83 patients including 25 patients with refractory MP pneumonia and 58 patients with macrolide responsive MP pneumonia. The percentages of circulating Th17 cells and Tregs were determined by flow cytometry. The concentrations of serum Th17- and Treg-related cytokines were measured by enzyme-linked immunosorbent assay (ELISA). In comparison with that in the patients with macrolide responsive MP pneumonia and healthy control, significantly higher frequencies of Th17 cells and higher levels of IL-17 were detected in patients with refractory MP pneumonia. But there are no significant difference with the frequencies of Tregs and the levels of TGF-ß1 in the patients with refractory MP pneumonia and patients with macrolide responsive MP pneumonia. However the Th17/Treg ratio was found to be significantly higher in the patients with refractory MP pneumonia than the patients with macrolide responsive MP pneumonia. An imbalance of circulating Th17 cells and Tregs is associated with the deterioration of pulmonary injury in patients with MP infections.

[Safety of implantation permanent pacemaker at different times in patients with dual antiplatelet therapy].

OBJECTIVE: To investigate the safety of implantation permanent pacemaker (PM) at different times in patients with dual antiplatelet (DAPT) therapy after implantation of drug-eluting stent (DES). METHODS: A total of 105 patients who implanted pacemakers with DAPT therapy (clopidogrel and aspirin) after implantation of DES admitted to our hospital from January 2009 to January 2015 were enrolled in the study. The patients were divided into 3 groups: dual antiplatelet therapy (DAP) group: implanting PM within 3 months after coronary stenting, continuous DAPT during perioperative period; low molecular weight heparin (LMWH) bridging group: implanting PM within 3 to 6 months after coronary stenting, DAPT interruption for 5 days replaced with subcutaneous injection of enoxaparin (1 mg/kg), twice per day, enoxaparin was stopped 12 h before operation; asprin group, implanting PM after coronary stenting 6 months, clopidogrel interruption for 5 days. Oral DAPT was returned 12-24 after operation according to the patients' condition. Peri-operative cardiovascular events and bleedings, infections were observed. RESULTS: There was no major adverse cardiac event (MACE) and pouch infection were observed among 3 groups in perioperation. The incidence of pocket hemorrhage and errhysis in bridging group was significantly higher than that of DAP group and asprin group (16.7%, 8.0%, 0.0% χ(2)=10.431, P=0.005 and 29.2%, 12.0%, 7.1% χ(2)=6.321, P=0.042 respectively). 3 patients had severe bleeding (12.5%, 3/24) in bridging group; compared with the other 2 groups, there were significant difference (χ(2)=9.161, P=0.010). The incidence of hematoma and hemorrhage of asprin group was lowest. CONCLUSIONS: LMWH bridging therapy significantly increases the risk of pacemaker pocket hematoma and hemorrhage, and the pacemaker implantation may be safer after DES implantation 6 months.

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice.

Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H×Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT.

A novel MVK missense mutation in one Chinese family with disseminated superficial actinic porokeratosis.

Disseminated superficial actinic porokeratosis (DSAP) is a severe chronic autosomal dominant cutaneous disorder with high genetic heterogeneity. mevalonate kinase, (MVK) a gene know to play an important role in regulation of calcium-induced keratinocyte differentiation and proliferation, has recently been suggested as the disease-causing gene for DSAP. Here we report a direct sequencing analysis of this gene in 3 DSAP families, 6 sporadic cases, and 100 unrelated healthy controls. We detected a heterozygous T to A transition at nucleotide 205 in exon 3 of MVK gene in one familial case. This mutation will result in an amino acid change at codon 69 (P.Ser69Thr), which is from a serine codon (TCA) to a threonine codon (ACA). No such mutation was detected in the unaffected family members or the 100 unrelated healthy controls. Our results demonstrated a novel missense mutation in MVK gene. This will be valuable for the diagnosis of DSAP as well as for genetic counseling and prenatal diagnosis of affected families.

Geographically weighted machine learning for modeling spatial heterogeneity in traffic crash frequency and determinants in US.

Spatial analyses of traffic crashes have drawn much interest due to the nature of the spatial dependence and spatial heterogeneity in the crash data. This study makes the best of Geographically Weighted Random Forest (GW-RF) model to explore the local associations between crash frequency and various influencing factors in the US, including road network attributes, socio-economic characteristics, and land use factors collected from multiple data sources. Special emphasis is put on modeling the spatial heterogeneity in the effects of a factor on crash frequency in different geographical areas in a data-driven way. The GW-RF model outperforms global models (e.g. Random Forest) and conventional geographically weighted regression, demonstrating superior predictive accuracy and elucidating spatial variations. The GW-RF model reveals spatial distinctions in the effects of certain factors on crash frequency. For example, the importance of intersection density varies significantly across regions, with high significance in the southern and northeastern areas. Low-grade road density emerges as influential in specific cities. The findings highlight the significance of different factors in influencing crash frequency across zones. Road network factors, particularly intersection density, exhibit high importance universally, while socioeconomic variables demonstrate moderate effects. Interestingly, land use variables show relatively lower importance. The outcomes could help to allocate resources and implement tailored interventions to reduce the likelihood of crashes.

Research situation, hot spots, and global trends of melasma therapy: Bibliometric insights and visual analysis from 2000 to 2023.

BACKGROUND: Melasma is a prevalent pigmented disease, yet its pathogenesis remains unclear, posing challenges for effective treatment. Bibliometric analysis, a novel approach to literature research, offers the opportunity to evaluate research trends through qualitative and quantitative methods. This study utilizes bibliometric methods to analyze the existing literature on melasma treatment, examining influential publications, institutions, countries, and authors through statistical analysis. METHODS: In order to retrieve manuscripts related to the topic of melasma treatment, we conducted a search using the search formula: (TS = (melasma or Chloasma or "mask of pregnancy")) AND TS = (treatment or therapy). We searched through the Web of Science Core Collection database, covering publications from 2000 to 2023. VOSviewer, CiteSpace and the Bibliometric online site (https://bibliometric.com/app) were used to conduct this bibliometric analysis. Our analysis focused on various factors including publications, authors co-authorship, institutions, countries, citation analysis, keywords co-occurrence, references co-citation and journal co-citation. RESULTS: A total of 943 articles and 200 reviews were published between 2000 and 2023, accumulating a total of 8628 citations. The average number of citations per item was 18.85, and the average number of citations per year was 292.69. The most prolific author, Sungeun Chang, contributed a total of 9 articles. Cario University emerged as the top research institution. The United States led in terms of article publications with a count of 276. In the past 5 years, the research trends in this field have primarily focused on tranexamic acid and epidermal melasma, as indicated by the burst analysis of publications and keywords. CONCLUSIONS: The United States continues to lead in terms of institutions and research output. The current emphasis is on the meticulous implementation of tranexamic acid and laser therapy. It is crucial to foster enhanced collaboration among countries, institutions, and authors to facilitate improved research.

Fibroblasts/three-dimensional scaffolds complexes promote wound healing in rats with skin defects.

We aim to construct a three-dimensional nano-skin scaffold material in vitro and study its promoting effect on wound healing in vivo. In this study, hybrid constructs of three-dimensional (3D) scaffolds were successfully fabricated by combination of type I collagen (COL-1) and polylactic-glycolic acid (PLGA). Fibroblasts and human umbilical cord mesenchymal stem cells (hUCMSCs) were used to implanted into 3D scaffolds and constructed into SD skin scaffolds in vitro. Finally, the fibroblasts/scaffolds complexes were inoculated on the surface of rat wound skin to study the promoting effect of the complex on wound healing. In our study, we successfully built a 3D scaffold, which had a certain porosity. Meanwhile, the content of COL-1 in the cell supernatant of fibroblast/scaffold complexes was increased. Furthermore, the expression of F-actin, CD105, integrin ß, VEGF, and COL-1 was up-regulated in hUCMSC/scaffold complexes compared with the control group. In vivo, fibroblast/scaffold complexes promoted wound healing in rats. Our data suggested that the collagen Ⅳ and vimentin were elevated and collagen fibers were neatly arranged in the fibroblast/scaffold complex group was significantly higher than that in the scaffold group. Taken together, fibroblast/scaffold complexes were expected to be novel materials for treating skin defects.

A meta-analysis of the efficacy of programmed cell death 1/its ligand inhibitors plus cytotoxic T-lymphocyte-associated antigen 4 inhibitors in non-small cell lung cancer.

Background: Immune checkpoint inhibitors (ICIs), either as monotherapy or in combination with chemotherapy, have improved the therapeutic outcome for non-small cell lung cancer (NSCLC). However, the efficacy of combination therapies, such as programmed cell death 1(PD-1)/its ligand (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, in targeting different pathways remains unclear. We performed a meta-analysis to determine whether the addition of a CTLA-4 inhibitor to PD-1/PD-L1 therapy improves the efficacy of PD-1/PD-L1 monotherapy in NSCLC. Methods: We systematically searched various electronic databases for suitable trials. Only randomized controlled trials (RCTs) comparing the clinical efficacy of PD-1/PD-L1 with and without CTLA-4 were included in the analyses. The meta-analysis software RevMan 5.3 was used for statistical analyses. Results: A total of seven RCTs were retrieved. The results suggested that the combination of CTLA-4 and PD-1/PDL-1 inhibitors did not show enhanced efficacy over PD1/PDL-1 inhibitor monotherapy as determined by overall survival (OS) (HR = 0.98, 95% CI = 0.84-1.14, p = 0.79), progression-free survival (PFS) (HR = 0.92, 95% CI = 0.81-1.06, p = 0.25), and objective response rate (ORR) (HR = 1.08, 95% CI = 0.96-1.21, p = 0.19). Furthermore, the combination immunotherapy was associated increased toxicity as evidenced by increased incidence of any type adverse events (AEs) (RR = 1.06, 95% CI = 1.00-1.13, p = 0.03), grade ≥3 immune-mediated AEs (RR = 1.58, 95% CI = 1.36-1.82, p < 0.05), and treatment discontinuation (RR = 1.83, 95% CI = 1.46-2.28, p < 0.05). Conclusion: Combining anti-CTLA-4 with anti-PD-1/PD-L1 therapy did not improve the therapeutic efficacy, and was associated with greater toxicity than anti-PD-1/PD-L1 monotherapy in patients with advanced NSCLC. Further investigation of the combination immunotherapy in specific subsets of patients is warranted to identify and define the patient-specific benefits of this combination. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023435399.

Development and trends in metabolomics studies in psoriasis: A bibliometric analysis of related research from 2011 to 2024.

Background: Psoriasis is a chronic, inflammatory skin disease with autoimmune characteristics. Recent research has made significant progress in the field of psoriasis metabolomics. However, there is a lack of bibliometric analysis on metabolomics of psoriasis. The objective of this study is to utilize bibliometrics to present a comprehensive understanding of the knowledge structure and research hotspots in psoriasis within the field of metabolomics. Methods: We conducted a bibliometric analysis by searching the Web of Science Core Collection database for publications on metabolomics in psoriasis from 2011 to 2024. To perform this analysis, we utilized tools such as VOSviewers, CiteSpace, and the R package "bibliometrix". Results: A total of 307 articles from 47 countries, with the United States and China leading the way, were included in the analysis. The publications focusing on metabolomics in psoriasis have shown a steady year-on-year growth. The Medical University of Bialystok is the main research institution. The International Journal of Molecular Sciences emerges as the prominent journal in the field, while the Journal of Investigative Dermatology stands out as the highly co-cited publication. A total of 2029 authors contributed to these publications, with Skrzydlewska Elzbieta, Baran Anna, Flisiak Iwona, Murakami Makoto being the most prolific contributors. Notably, Armstrong April W. received the highest co-citation. Investigating the mechanisms of metabolomics in the onset and progression of psoriasis, as well as exploring therapeutic strategies, represents the primary focus of this research area. Emerging research hotspots encompass inflammation, lipid metabolism, biomarker, metabolic syndrome, obesity, and arthritis. Conclusion: The results of this study indicate that metabolism-related research is thriving in psoriasis, with a focus on the investigation of metabolic targets and interventions within the metabolic processes. Metabolism is expected to be a hot topic in future psoriasis research.

Diabetes mellitus and increased risk of extrahepatic cholangiocarcinoma: a meta-analysis.

BACKGROUND/AIMS: Diabetes mellitus (DM) has been considered to be relevant to an increased risk of several different types of cancers. However, its relationship with extrahepatic cholangiocarcinoma (ECC) remains unclear. METHODOLOGY: To investigate a quantitative assessment of this relationship, we performed a meta-analysis to evaluate the association between diabetes and the risk of ECC. We identified studies by searching Embase (from 1 January 1974 to 30 June 2012), Medline (from 1 January 1966 to 30 June 2012), and the reference lists of related articles. Summary relative risks (RRs) with corresponding 95% CIs were calculated with a random-effects model. RESULTS: A total of 9 articles (4 case-control and 5 cohort studies) were included in this study. Compared with those without DM, individuals with DM had an increased risk of ECC (for case-control studies: summary OR=1.61, 95% CI: 1.05-2.49, p=0.063 for heterogeneity; for cohort studies: summary RR=1.61, 95% CI: 1.14-2.29, p=0.005 for heterogeneity). The funnel plot showed no evidence for publication bias concerning DM and the risk of ECC (Egger's test, p=0.699; Begg's test, p=0.175). CONCLUSIONS: These findings strongly reveal the positive link between DM and the increased risk of ECC.