Spatial whole exome sequencing reveals the genetic features of highly-aggressive components in lung adenocarcinoma.

In invasive lung adenocarcinoma (LUAD), patients with micropapillary (MIP) or solid (SOL) components had a significantly poorer prognosis than those with only lepidic (LEP), acinar (ACI) or papillary (PAP) components. It is interesting to explore the genetic features of different histologic subtypes, especially the highly aggressive components. Based on a cohort of 5,933 patients, this study observed that in different tumor size groups, LUAD with MIP/SOL components showed a different prevalence, and patients with ALK alteration or TP53 mutations had a higher probability of developing MIP/SOL components. To control individual differences, this research used spatial whole-exome sequencing (WES) via laser-capture microdissection of five patients harboring these five coexistent components and identified genetic features among different histologic components of the same tumor. In tracing the evolution of components, we found that titin (TTN) mutation might serve as a crucial intratumor potential driver for MIP/SOL components, which was validated by a cohort of 146 LUAD patients undergoing bulk WES. Functional analysis revealed that TTN mutations enriched the complement and coagulation cascades, which correlated with the pathway of cell adhesion, migration, and proliferation. Collectively, the histologic subtypes of invasive LUAD were genetically different, and certain trunk genotypes might synergize with branching TTN mutation to develop highly aggressive components.

PTEN status determines therapeutic vulnerability to celastrol in cholangiocarcinoma.

BACKGROUND: A balanced protein homeostasis network helps cholangiocarcinoma (CCA) maintain their oncogenic growth, and disrupting proteostasis therapeutically will induce proteotoxic stress. Phosphatase and tensin homolog (PTEN) have been reported to be involved in proteostasis, and PTEN-associated pathways are commonly altered in CCA. Celastrol, a triterpene from plants, exhibits cytotoxic effects in various types of cancer. However, the underlying mechanisms remain unclear. PURPOSE: We investigated the therapeutic effect of celastrol in CCA and identified the molecular characteristics of tumors that were sensitive to celastrol. The target of celastrol was explored. We then evaluated the candidate combination therapeutic strategy to increase the effectiveness of celastrol in celastrol-insensitive CCA tumors. METHODS: Various CCA cells were categorized as either celastrol-sensitive or celastrol-insensitive based on their response to celastrol. The molecular characteristics of cells from different groups were determined by RNA-seq. PTEN status and its role in proteasome activity in CCA cells were investigated. The CMAP analysis, molecular docking, and functional assay were performed to explore the effect of celastrol on proteasome activities. The correlation between PTEN status and clinical outcomes, as well as proteasomal activity, were measured in CCA patients. The synergistic therapeutic effect of autophagy inhibitors on celastrol-insensitive CCA cells were measured. RESULTS: Diverse responses to celastrol were observed in CCA cells. PTEN expression varied among different CCA cells, and its status could impact cell sensitivity to celastrol: PTENhigh tumor cells were resistant to celastrol, while PTENlow cells were more sensitive. Celastrol induced proteasomal dysregulation in CCA cells by directly targeting PSMB5. Cells with low PTEN status transcriptionally promoted proteasome subunit expression in an AKT-dependent manner, making these cells more reliant on proteasomal activities to maintain proteostasis. This caused the PTENlow CCA cells sensitive to celastrol. A negative correlation was found between PTEN levels and the proteasome signature in CCA patients. Moreover, celastrol treatment could induce autophagy in PTENhigh CCA cells. Disrupting the autophagic pathway in PTENhigh CCA cells enhanced the cytotoxic effect of celastrol. CONCLUSION: PTEN status in CCA cells determines their sensitivity to celastrol, and autophagy inhibitors could enhance the anti-tumor effect in PTENhigh CCA.

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer.

As a highly invasive malignancy, esophageal cancer (EC) is a global health issue, and was the eighth most prevalent cancer and the sixth leading cause of cancer-related death worldwide in 2020. Due to its highly immunogenic nature, emer-ging immunotherapy approaches, such as immune checkpoint blockade, have demonstrated promising efficacy in treating EC; however, certain limitations and challenges still exist. In addition, tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment (TIME); thus, understanding the TIME is urgent and crucial, especially given the im-portance of an immunosuppressive microenvironment in tumor progression. The aim of this review was to better elucidate the mechanisms of the suppressive TIME, including cell infiltration, immune cell subsets, cytokines and signaling pathways in the tumor microenvironment of EC patients, as well as the downregulated expression of major histocompatibility complex molecules in tumor cells, to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies. Therefore, personalized treatments could be developed to maximize the advantages of immunotherapy.

Down-regulation of RTEL1 Improves M1/M2 Macrophage Polarization by Promoting SFRP2 in Fibroblasts-derived Exosomes to Alleviate COPD.

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease worldwide. Macrophage polarization plays a substantial role in the pathogenesis of COPD. This study is aimed to explore the regulatory mechanism of regulator of telomere elongation 1 (RTEL1) in COPD. COPD model mouse was conducted by cigarette smoke (CS). The pathological features of lung in mice were observed by histological staining. After extracting exosomes, macrophages were co-cultured with fibroblasts-derived exosomes. Then, the effects of RTEL1 and exosomal secreted frizzled-related protein 2 (SFRP2) on macrophage proliferation, inflammation, apoptosis, and M1, M2 macrophage polarization (iNOS and CD206) were evaluated by cell counting kit-8, EdU assay, enzyme-linked immuno sorbent assay, and western blotting, respectively. CS-induced COPD model mouse was successfully constructed. Through in vitro experiments, knockdown of RTEL1 inhibited macrophage proliferation, inflammation (MMP9, IL-1ß and TNF-α), and promoted apoptosis (Bax, cleaved-caspase3, Bcl-2) in CS extract-induced lung fibroblasts. Meanwhile, RTEL1 knockdown promoted M1 and suppressed M2 macrophage polarization in COPD. Additionally, silencing SFRP2 in fibroblasts-derived exosomes reversed the effects of RTEL1 knockdown on proliferation, inflammation, apoptosis, and M1, M2 macrophage polarization. Collectively, down-regulation of RTEL1 improved M1/M2 macrophage polarization by promoting SFRP2 in fibroblasts-derived exosomes to alleviate CS-induced COPD.

Efficacy and safety of eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with anthracycline/taxanes.

BACKGROUND: This prospective real-world study aimed to assess the efficacy and safety of eribulin in the clinical practice against advanced breast cancer (ABC) in China. PATIENTS AND METHODS: In this study, eligible patients with inoperable locally advanced or metastatic breast cancer who had experienced prior neo-/adjuvant or failed the palliative treatment with anthracycline/taxanes were included. Eribulin (1.4 mg/m2) was infused intravenously on Day 1 and Day 8 every 3 weeks until disease progression or intolerable toxicity occurred. The progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and safety of the treatment were assessed. RESULTS: One hundred and thirty-four patients were enrolled. The median PFS (mPFS) was 4.3 months (95% CI: 0.3-15.4). The ORR and DCR was 32.1% and 79.1%, respectively. The mPFS of patients who received eribulin as first- or second-line treatment was significantly better than those who received eribulin as ≥3-line treatment (6.9 months [95% CI: 3.2-8.8] vs. 4.0 months [95% CI: 3.4-4.6], p = 0.006). The mPFS of patients with triple-negative, HER2-positive, and HER2(-)/HR(+) was 3.4 (95% CI: 2.7-4.1), 6.2 (95% CI: 2.3-10.1) and 5.0 months (95% CI: 4.1-5.9), respectively. HER2(+) patients had significantly longer PFS than TNBC patients (p = 0.022). Patients received combination therapy had a significantly longer mPFS than those who received eribulin monotherapy (5.0 months [95% CI 3.6-6.3] vs. 4.0 months [95% CI: 3.3-4.7] [p = 0.016]). Multivariate analysis revealed that MBC patients with a molecular typing of non-TNBC receiving eribulin as ≤2-line therapy and combination therapy had a low risk of disease progression. Neutropenia (33.58%), leukopenia (11.94%), and thrombocytopenia (4.48%) were the most common treatment-related adverse events. CONCLUSION: Eribulin demonstrated effective clinical activity and a favorable tolerability profile in Chinese patients with ABC in the real-world. The efficacy and safety profile were consistent with those reported in previous randomized phase 3 trials.

Unveiling the role of the KLF4/Lnc18q22.2/ULBP3 axis in the tumorigenesis and immune escape of hepatocellular carcinoma under hypoxic condition.

Hepatocellular carcinoma (HCC) represents a significant global health burden, necessitating an in-depth exploration of its molecular underpinnings to facilitate the development of effective therapeutic strategies. This investigation delves into the complex role of long non-coding RNAs (lncRNAs) in the modulation of hypoxia-induced HCC progression, with a specific emphasis on delineating and functionally characterizing the novel KLF4/Lnc18q22.2/ULBP3 axis. To elucidate the effects of hypoxic conditions on HCC cells, we established in vitro models under both normoxic and hypoxic environments, followed by lncRNA microarray analyses. Among the lncRNAs identified, Lnc18q22.2 was found to be significantly upregulated in HCC cells subjected to hypoxia. Subsequent investigations affirmed the oncogenic role of Lnc18q22.2, highlighting its critical function in augmenting HCC cell proliferation and migration. Further examination disclosed that Kruppel-like factor 4 (KLF4) transcriptionally governs Lnc18q22.2 expression in HCC cells, particularly under hypoxic stress. KLF4 subsequently enhances the tumorigenic capabilities of HCC cells through the modulation of Lnc18q22.2 expression. Advancing downstream in the molecular cascade, our study elucidates a novel interaction between Lnc18q22.2 and UL16-binding protein 3 (ULBP3), culminating in the stabilization of ULBP3 protein expression. Notably, ULBP3 was identified as a pivotal element, exerting dual functions by facilitating HCC tumorigenesis and mitigating immune evasion in hypoxia-exposed HCC cells. The comprehensive insights gained from our research delineate a hitherto unidentified KLF4/Lnc18q22.2/ULBP3 axis integral to the understanding of HCC tumorigenesis and immune escape under hypoxic conditions. This newly unveiled molecular pathway not only enriches our understanding of hypoxia-induced HCC progression but also presents novel avenues for therapeutic intervention.

Persistence of SARS-CoV-2 colonization and high expression of inflammatory factors in cardiac tissue 6 months after COVID-19 recovery: a prospective cohort study.

Background: The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in myocardial autopsy tissues has been observed in certain individuals with coronavirus disease 2019 (COVID-19). However, the duration of cardiac involvement remains uncertain among recovered COVID-19 patients. Our study aims to evaluate the long-term persistence of SARS-CoV-2 within cardiac tissue. Methods: We prospectively and consecutively evaluated the patients undergoing mitral valve replacement (MVR) and left atrial (LA) volume reduction surgery from May 25 to June 10, 2023 at our center, who had been approximately 6 months of recovery after Omicron wave. Patients tested positive for SARS-CoV-2 upon admission were excluded. The surgical LA tissue was collected in RNA preservation solution and stored at -80 ℃ immediately. Then SARS-CoV-2, interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) RNA expression in LA tissues were assessed through thrice-repeated reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Categorical variables were assessed using the Chi-square or Fisher's exact tests, and continuous variables was analyzed using the Mann-Whitney U test. Results: Nine of 41 patients were enrolled, all of whom tested negative for SARS-CoV-2 upon admission (two antigen and PCR tests). In four of nine patients, SARS-CoV-2 RNA was detected in their LA tissue, indicating viral colonization. Among the four positive cases, the IL-6 and IL-1ß relative expression levels in the LA tissue of one patient were increased approximately 55- and 110-fold, respectively, compared to those of SARS-CoV-2 (-) patients. Increased expression of IL-6 and IL-1ß were observed in the myocardium of this patient. Another patient demonstrated a remarkable 7-fold increase in both IL-6 and IL-1ß expression, surpassing that of SARS-CoV-2 (-) patients. Additionally, no other cardiac inflammation-related diseases or conditions were presented in these two patients. The IL-6 and IL-1ß expression levels of the remaining two patients were not significantly different from those of SARS-CoV-2 (-) patients. The relative expression levels of IL-6 and IL-1ß in cardiac tissues of all SARS-CoV-2 (-) patients were relatively low. Interestingly, despite abnormally elevated levels of IL-6 and IL-1ß within their cardiac tissue, two patients did not show a significant increase in serum IL-6 and IL-1ß levels when compared to other patients. Conclusions: Our research suggests that certain COVID-19-recovered patients have persistent colonization of SARS-CoV-2 in their cardiac tissue, accompanied by a local increase in inflammatory factors.

B-ultrasound-assisted gluteal fat grafting in Asians: A prospective study of quantitative results from three-dimensional imaging and B-ultrasound analysis.

BACKGROUND: The increasing number of fatalities caused by gluteal fat grafting is concerning; thus, there is a need to determine ways to obtain the ideal aesthetic effect while ensuring a safe operation. In this study, three-dimensional (3D) measurements combined with B-ultrasound were used to evaluate the effect of gluteal fat augmentation in Asians, whose safety and effectiveness were confirmed using quantitative data. METHODS: Thirty-five consecutive female patients were evaluated in this prospective clinical study. All patients underwent B-ultrasound-assisted gluteal fat augmentation on the subcutaneous plane alone. 3D imaging and B-ultrasound analysis of the adipose tissue thickness in the gluteal region were performed preoperatively and at 1 week, 3 months and 6 months post-operatively. RESULTS: The waist circumference of the patients decreased, gluteal circumference and length of the gluteal crease increased and average waist-to-hip ratio improved from 0.78 to 0.74. At 3 months and 6 months post-operatively, the adipose tissue thickness decreased by 5.1% and 15.1%, respectively. The fat retention rates calculated using 3D imaging measurements at 3 months and 6 months post-operatively were 77.9% and 64.7%, respectively. According to the BODY-Q scale scores, patients reported a high level of satisfaction post-operatively. CONCLUSIONS: B-ultrasound guidance can effectively prevent the occurrence of fatal fat embolism during gluteal fat grafting and maximise the augmentation effect. The quantitative data obtained using 3D measurements and B-ultrasound confirmed the safety and effectiveness of fat injections for gluteal augmentation under B-ultrasound guidance.

Cannabidiol alleviates carbon tetrachloride-induced liver fibrosis in mice by regulating NF-κB and PPAR-α pathways.

Liver fibrosis has become a serious public health problem that can develop into liver cirrhosis and hepatocellular carcinoma and even lead to death. Cannabidiol (CBD), which is an abundant nonpsychoactive component in the cannabis plant, exerts cytoprotective effects in many diseases and under pathological conditions. In our previous studies, CBD significantly attenuated liver injury induced by chronic and binge alcohol in a mouse model and oxidative bursts in human neutrophils. However, the effects of CBD on liver fibrosis and the underlying mechanisms still need to be further explored. A mouse liver fibrosis model was induced by carbon tetrachloride (CCl4) for 10 weeks and used to explore the protective properties of CBD and related molecular mechanisms. After the injection protocol, serum samples and livers were used for molecular biology, biochemical and pathological analyses. The results showed that CBD could effectively improve liver function and reduce liver damage and liver fibrosis progression in mice; the expression levels of transaminase and fibrotic markers were reduced, and histopathological characteristics were improved. Moreover, CBD inhibited the levels of inflammatory cytokines and reduced the protein expression levels of p-NF-κB, NF-κB, p-IκBα, p-p38 MAPK, and COX-2 but increased the expression level of PPAR-α. We found that CBD-mediated protection involves inhibiting NF-κB and activating PPAR-α. In conclusion, these results suggest that the hepatoprotective effects of CBD may be due to suppressing the inflammatory response in CCl4-induced mice and that the NF-κB and PPAR-α signaling pathways might be involved in this process.

Clinical relevance of somatic mutations in Chinese lung adenocarcinoma and their prognostic implications for survival.

BACKGROUND: To comprehensively elucidate the genomic and mutational features of lung cancer cases, and lung adenocarcinoma (LUAD), it is imperative to conduct ongoing investigations into the genomic landscape. In this study, we aim to analyze the somatic mutation profile and assessed the significance of these informative genes utilizing a retrospective LUAD cohort. METHODS: A total of 247 Chinese samples were analyzed to exhibit the tumor somatic genomic alterations in patients with LUAD. The Cox regression analysis was employed to identify prognosis-related genes and establish a predictive model for stratifying patients with LUAD. RESULTS: In the Dianjiang People's Hospital (DPH) cohort, the top five frequent mutated genes were (Epidermal growth factor receptor) EGFR (68%), TP53 (30%), RBM10 (13%), LRP1B (9%), and KRAS (9%). Of which, EGFR is a mostly altered driver gene, and most mutation sites are located in tyrosine kinase regions. Oncogene pathway alteration and mutation signature analysis demonstrated the RTK-RAS pathway alteration, and smoking was the main carcinogenic factor of the DPH cohort. Furthermore, we identified 34 driver genes in the DPH cohort, including EGFR (68%), TP53 (30.4%), RBM10 (12.6%), KRAS (8.5%), LRP1B (8.5%), and so on, and 45 Clinical Characteristic-Related Genes (CCRGs) were found to closely related to the clinical high-risk factors. We developed a Multiple Parameter Gene Mutation (MPGM) risk model by integrating critical genes and oncogenic pathway alterations in LUAD patients from the DPH cohort. Based on publicly available LUAD datasets, we identified five genes, including BRCA2, Anaplastic lymphoma kinase (ALK), BRAF, EGFR, and Platelet-Derived Growth Factor Receptor Alpha (PDGFRA), according to the multivariable Cox regression analysis. The MPGM-low group showed significantly better overall survival (OS) compared to the MPGM-high group (p < 0.0001, area under the curve (AUC) = 0.754). The robust performance was validated in 55 LUAD patients from the DPH cohort and another LUAD dataset. Immune characteristics analysis revealed a higher proportion of primarily DCs and mononuclear cells in the MPGM-low risk group, while the MPGM-high risk group showed lower immune cells and higher tumor cell infiltration. CONCLUSION: This study provides a comprehensive genomic landscape of Chinese LUAD patients and develops an MPGM risk model for LUAD prognosis stratification. Further follow-up will be performed for the patients in the DPH cohort consistently to explore the resistance and prognosis genetic features.

Clinicopathologic factors correlated with lymph node metastasis in gastric cancer: a retrospective cohort study involving 5606 patients.

BACKGROUND: The identification of risk factors associated with lymph node metastasis (LNM) in gastric cancer will establish a crucial foundation for the implementation of endoscopic operation and multidisciplinary treatment programs. METHODS: A total of 5606 patients with gastric cancer with comprehensive clinicopathologic data were enrolled through systematic searching and rigorous screening. Of the 5606 patients, 1438 were diagnosed with early gastric cancer (EGC), which would be used for further analysis. Subsequently, univariate and multivariate logistic regression analyses were performed to identify the risk factors. RESULTS: The rates of LNM in T1a, T1b, T2, T3, T4a, and T4b stage gastric cancer were 7.0%, 19.4%, 48.4%, 77.1%, 83.8%, and 89.6%, respectively. Female (odds ratio [OR], 1.559; P = .032), lower tumor location (OR, 1.773; P = .023), tumor size of >2 cm (OR, 2.007; P < .001), mixed (OR, 2.371; P = .001) and undifferentiated histologic types (OR, 2.952; P < .001), T1b stage (OR, 2.041; P < .001), presence of ulceration (OR, 1.758; P = .027), and lymphovascular invasion (OR, 5.722; P < .001) were identified as independent risk factors for LNM in EGC. A nomogram was constructed using appropriate predictors to preoperatively predict the risk of LNM in patients with EGC. CONCLUSION: This study identified the clinicopathologic factors associated with LNM in patients with EGC and developed a prediction model, thereby facilitating the integration of diverse treatment modalities in managing patients with EGC.

Sub-lobar resection versus lobectomy for challenging intraoperative frozen sections in lung adenocarcinoma within 3 cm.

OBJECTIVES: Intraoperative frozen section (FS) analysis is pivotal in guiding surgical interventions for early-stage lung adenocarcinoma. However, the challenge arises when distinguishing between Minimally Invasive Adenocarcinoma (MIA) and Invasive Adenocarcinoma (IAC) poses diagnostic difficulties. This study investigates the prognosis and clinicopathological characteristics of patients encountering this diagnostic challenge. METHODS: We conducted a retrospective analysis of 7082 intraoperative FSs from early-stage lung adenocarcinoma cases. The cases with pulmonary nodules within 3 cm and diagnosed as indeterminate FSs were included. We analyzed baseline data, computed tomography (CT) findings, and pathological characteristics. Prognostic data were obtained from patients with confirmed IAC diagnoses through final pathological examination. RESULTS: Out of 7082 FSs, 551 cases presented challenges in distinguishing between MIA and IAC. Upon final pathological examination, 233 cases were identified as IAC, while 314 were classified as MIA. The median invasive pathological size in the IAC group was larger than that in the MIA group (0.6 cm vs 0.3 cm). 131 cases (56.2 %) with IAC underwent lobectomy, while 102 cases (43.8 %) underwent sub-lobar resection. Among the MIA cases, 220 cases (69.8 %) underwent sub-lobar resection, while 95 cases (30.2 %) underwent lobectomy. No recurrence and disease specific death was observed during the follow-up period, regardless of surgical strategy. CONCLUSIONS: Indeterminate intraoperative FSs, posing diagnostic challenges in distinguishing between MIA and IAC. Sub-lobar resection presented the same long term survival benefit compared with the lobectomy for indeterminate lung adenocarcinoma within 3 cm during intraoperative FSs.

Characterization of genital chlamydia trachomatis infection among women attending infertility and gynecology clinics in Hunan, China.

BACKGROUND: Genital infection with Chlamydia trachomatis (C. trachomatis) is a major public health issue worldwide. It can lead to cervicitis, urethritis, and infertility. This study was conducted to determine the characteristics of genital C. trachomatis infection among women attending to the infertility and gynecology clinics. METHODS: Endocervical swabs were collected from 8,221 women for C. trachomatis nucleotide screening and genotyping, while serum samples were collected for C. trachomatis pgp3 antibody determination using luciferase immunosorbent assays. RESULTS: High C. trachomatis DNA prevalence (3.76%) and seroprevalence (47.46%) rates were found, with genotype E (27.5%) being the most prevalent. C. trachomatis omp1 sense mutation was associated with cervical intraepithelial neoplasia (CIN) (odds ratio [OR] = 6.033, 95% confidence interval [CI] = 1.219-39.185, p = 0.045). No significant differences in C. trachomatis seroprevalence rates were observed between women with detectable C. trachomatis DNA in the infertility and routine physical examination groups (86.67% vs. 95%, p > 0.05); however, among women with negative C. trachomatis DNA, the former group had a markedly higher seroprevalence than the latter group (56.74% vs. 20.17%, p < 0.001). C. trachomatis DNA, but not pgp3 antibody, was significantly associated with CIN (OR = 4.087, 95% CI = 2.284-7.315, p < 0.001). CONCLUSION: Our results revealed a high prevalence, particularly seroprevalence, of C. trachomatis among women with infertility. Furthermore, we found an association between C. trachomatis omp1 sense mutations and CIN. Therefore, C. trachomatis serves as a risk factor for CIN.

A new minimal invasive technique with in-situ stent-graft fenestration for type A aortic dissection.

Background: Aortic surgery successfully improves the prognosis of patients with type A aortic dissection. However, total arch replacement and reconstruction remain challenging. This study presents a new surgical modality, the in-situ stent-graft fenestration (ISSF) technique, for simplifying aortic arch reconstruction and assesses its short-term efficacy and safety in patients with type A aortic dissection. Methods: Data from 177 patients with type A aortic dissection who underwent aortic arch reconstruction were retrospectively analyzed. Sun's procedure was performed in 90 patients and ISSF was performed in the other 87. Results: The in-hospital mortality rate was 7.8% in the Sun's procedure group and 3.4% in the ISSF group (p = 0.357). Compared to the Sun's procedure group, the ISSF group had significantly shorter surgical duration, cardiopulmonary bypass time, circulatory arrest time, mechanical ventilation time, and aortic cross-clamp time (p < 0.05). Additionally, intraoperative blood loss was lower in the ISSF group than in the Sun's procedure group (p < 0.05). Patients who underwent ISSF also had a lower incidence of postoperative complications, including lung injury, renal failure, peripheral nerve injury, and chylothorax, than those who underwent Sun's procedure (p < 0.05). During the 6-month follow-up period after surgery, both groups showed significant improvements in the true lumen diameter of the descending thoracic aorta post-operation compared with the pre-operation measurements; meanwhile, the false lumen diameter decreased (p < 0.05). Conclusions: The ISSF technique appears to be an effective and safe alternative to conventional surgical procedures for patients with type A aortic dissection, with the potential to simplify the procedure, shorten the operation time, and yield satisfactory operative results. However, further investigation is needed to determine its long-term benefits.

The chest X-ray score baseline in predicting continuous oxygen therapy failure in low-risk aged patients after thoracic surgery.

Background: Radiographic severity assessment can be instrumental in diagnosing postoperative pulmonary complications (PPCs) and guiding oxygen therapy. The radiographic assessment of lung edema (RALE) and Brixia scores correlate with disease severity, but research on low-risk elderly patients is lacking. This study aimed to assess the efficacy of two chest X-ray scores in predicting continuous oxygen therapy (COT) treatment failure in patients over 70 years of age after thoracic surgery. Methods: From January 2019 to December 2021, we searched for patients aged 70 years and above who underwent thoracic surgery and received COT treatment, with a focus on those at low risk of respiratory complications. Bedside chest X-rays, RALE, Brixia scores, and patient data were collected. Univariate, multivariate analyses, and 1:2 matching identified risk factors. Receiver operating characteristic (ROC) curves determined score sensitivity, specificity, and predictive values. Results: Among the 242 patients surviving to discharge, 19 (7.9%) patients experienced COT failure. COT failure correlated with esophageal cancer surgeries, thoracotomies (36.8% vs. 9%, P=0.003; 26.3% vs. 9.4%, P=0.004), and longer operation time (3.4 vs. 2.8 h, P=0.003). Surgical approach and RALE score were independent risk factors. The prediction model had an area under the curve (AUC) of 0.839 [95% confidence interval (CI), 0.740-0.938]. Brixia and RALE scores predicted COT failure with AUCs of 0.764 (95% CI, 0.650-0.878) with a cut-off value of 6.027 and 0.710 (95% CI, 0.588-0.832) with a cut-off value of 17.134, respectively, after 1:2 matching. Conclusions: The RALE score predict the risk of COT failure in elderly, low-risk thoracic patients better than the Brixia score. This simple, cheap, and noninvasive method helps evaluate postoperative lung damage, monitor treatment response, and provide early warning for oxygen therapy escalation. Further studies are required to confirm the validity and applicability of this model in different settings and populations.

Tobacco toxins trigger bone marrow mesenchymal stem cells aging by inhibiting mitophagy.

Smoking disrupts bone homeostasis and serves as an independent risk factor for the development and progression of osteoporosis. Tobacco toxins inhibit the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), promote BMSCs aging and exhaustion, but the specific mechanisms are not yet fully understood. Herein, we successfully established a smoking-related osteoporosis (SROP) model in rats and mice through intraperitoneal injection of cigarette smoke extract (CSE), which significantly reduced bone density and induced aging and inhibited osteogenic differentiation of BMSCs both in vivo and in vitro. Bioinformatics analysis and in vitro experiments confirmed that CSE disrupts mitochondrial homeostasis through oxidative stress and inhibition of mitophagy. Furthermore, we discovered that CSE induced BMSCs aging by upregulating phosphorylated AKT, which in turn inhibited the expression of FOXO3a and the Pink1/Parkin pathway, leading to the suppression of mitophagy and the accumulation of damaged mitochondria. MitoQ, a mitochondrial-targeted antioxidant and mitophagy agonist, was effective in reducing CSE-induced mitochondrial oxidative stress, promoting mitophagy, significantly downregulating the expression of aging markers in BMSCs, restoring osteogenic differentiation, and alleviating bone loss and autophagy levels in CSE-exposed mice. In summary, our results suggest that BMSCs aging caused by the inhibition of mitophagy through the AKT/FOXO3a/Pink1/Parkin axis is a key mechanism in smoking-related osteoporosis.

Spatiotemporal distribution of mediastinal neoplasms: A comprehensive multi-center study.

OBJECTIVES: Mediastinal neoplasms are typical but uncommon thoracic diseases with increasing incidence and unfavorable prognoses. A comprehensive understanding of their spatiotemporal distribution is essential for accurate diagnosis and timely treatment. However, previous studies are limited in scale and data coverage. Therefore, this study aims to elucidate the distribution of mediastinal lesions, offering valuable insights into this disease. MATERIALS AND METHODS: This multi-center, hospital-based observational study included 20 nationwide institutions. A retrospective search of electronic medical records from January 1st, 2009, to December 31st, 2020, was conducted, collecting sociodemographic data, computed tomography images, and pathologic diagnoses. Analysis focused on age, sex, time, location, and geographical region. Comparative assessments were made with global data from a multi-center database. RESULTS: Among 7,765 cases, thymomas (30.7%), benign mediastinal cysts (23.4%), and neurogenic tumors (10.0%) were predominant. Distribution varied across mediastinal compartments, with thymomas (39.6%), benign cysts (28.1%), and neurogenic tumors (51.9%) most prevalent in the prevascular, visceral, and paravertebral mediastinum, respectively. Age-specific variations were notable, with germ cell tumors prominent in patients under 18 and aged 18-29, while thymomas were more common in patients over 30. The composition of mediastinal lesions across different regions of China remained relatively consistent, but it differs from that of the global population. CONCLUSION: This study revealed significant heterogeneity in the spatiotemporal distribution of mediastinal neoplasms. These findings provide useful demographic data when considering the differential diagnosis of mediastinal lesions, and would be beneficial for tailoring disease prevention and control strategies.

Construction of ceRNA network mediated by circRNAs screening from microarray and identification of novel biomarkers for myasthenia gravis.

BACKGROUND: Recent studies have revealed that circRNA can serve as ceRNA to participate in multiple autoimmune diseases. Our study aims to explore the key circRNA as ceRNA and biomarker for MG. METHODS: We used circRNA microarray to explore differentially expressed circRNAs (DECs) from MG and compare with control. Then, we predicted the target miRNA associated with DECs and screened miRNAs by the algorithm of random walk with restart (RWR). Next, we constructed the circRNA-miRNA-mRNA ceRNA regulated network (CMMC) to identify the hub objects. Following, we detected the expression of hub-circRNAs by RT-PCR. We verify has_circ_0004183 (circFRMD4) sponging miR-145-5p regulate cells proliferation using luciferase assay and CCK-8. RESULTS: We found that the expression level of circFRMD4 and has_circ_0035381 (circPIGB) were upregulated and has_circ_0089153(circ NUP214) had the lowest expression level in MG. Finally, we proved circFRMD4 sponging miR-145-5p regulate Jurkat cells proliferation. CircFRMD4 take part in the genesis and development of MG via circFRMD4/miR145-5p axis. CONCLUSIONS: We found that circFRMD4, circPIGB and circNUP214 can be considered as valuable potential novel biomarkers for AchR + MG. CircFRMD4 participate in the development of AchR + MG via targeting binding with miR-145-5p.

Macrophage-derived exosomal miRNA-141 triggers endothelial cell pyroptosis by targeting NLRP3 to accelerate sepsis progression.

Sepsis, critical condition marked by severe organ dysfunction from uncontrolled infection, involves the endothelium significantly. Macrophages, through paracrine actions, play a vital role in sepsis, but their mechanisms in sepsis pathogenesis remain elusive. Objective: We aimed to explore how macrophage-derived exosomes with low miR-141 expression promote pyroptosis in endothelial cells (ECs). Exosomes from THP-1 cell supernatant were isolated and characterized. The effects of miR-141 mimic/inhibitor on apoptosis, proliferation, and invasion of Human Umbilical Vein Endothelial Cells (HUVECs) were assessed using flow cytometry, CCK-8, and transwell assays. Key pyroptosis-related proteins, including caspase-1, IL-18, IL-1ß, NLR Family Pyrin Domain Containing 3 (NLRP3), ASC, and cleaved-GSDMD, were analyzed via Western blot. The interaction between miR-141 and NLRP3 was studied using RNAhybrid v2.2 and dual-Luciferase reporter assays. The mRNA and protein level of NLRP3 after exosomal miR-141 inhibitor treatment was detected by qPCR and Western blot, respectively. Exosomes were successfully isolated. miR-141 mimic reduced cell death and pyroptosis-related protein expression in HUVECs, while the inhibitor had opposite effects, increasing cell death, and enhancing pyroptosis protein expression. Additionally, macrophage-derived exosomal miR-141 inhibitor increased cell death and pyroptosis-related proteins in HUVECs. miR-141 inhibits NLRP3 transcription. Macrophages facilitate sepsis progression by secreting miR-141 decreased exosomes to activate NLRP3-mediated pyroptosis in ECs, which could be a potentially valuable target of sepsis therapy.