Long-term survival outcomes of esophagectomy with off-pump CABG versus esophagectomy alone.

BACKGROUND: This study aimed to evaluate the long-term survival outcomes of esophagectomy with off-pump coronary artery bypass grafting (OPCABG) vs. esophagectomy alone. METHODS: A total of 1798 patients who received esophagectomy between January 2010 and February 2020 were included and divided into the 38 patients who underwent OPCABG followed by esophagectomy (OP + ES group) and 1760 patients had only esophagectomy (ES group). Propensity score matching (PSM) and Cox multivariable analyses were performed to compare postoperative complications, disease-free survival (DFS), and overall survival (OS) between the two groups. RESULTS: There were 37 patients in the OP + ES group matched with 74 in the ES group. The matched OP + ES group had higher total postoperative complications than the ES group, especially more pulmonary infections (P = 0.001) and arrhythmias (P = 0.018), but no other postoperative complications were the difference. The DFS was similar and the OS was a significant difference between the matching 2 groups (log-rank, P = 0.132 and 0.04, respectively). Although pT 3/4 stage, pN (+), and tumor length > 3.0 cm were independently associated with worse OS and DFS in multivariable analysis, CAD and EF < 55% were also found to be a predictive factor for OS and DFS in univariate analysis. CONCLUSION: OPCABG followed by esophagectomy for esophageal cancer associated with coronary artery disease has equivalent DFS and recurrence pattern to esophagectomy for esophageal cancer alone, but with a disadvantage in OS.

Fused in sarcoma (FUS) inhibits milk production efficiency in mammals.

Efficient milk production in mammals confers evolutionary advantages by facilitating the transmission of energy from mother to offspring. However, the regulatory mechanism responsible for the gradual establishment of milk production efficiency in mammals, from marsupials to eutherians, remains elusive. Here, we find that mammary gland of the marsupial sugar glider contained milk components during adolescence, and that mammary gland development is less dynamically cyclic compared to that in placental mammals. Furthermore, fused in sarcoma (FUS) is found to be partially responsible for this establishment of low efficiency. In mouse model, FUS inhibit mammary epithelial cell differentiation through the cyclin-dependent kinase inhibitor p57Kip2, leading to lactation failure and pup starvation. Clinically, FUS levels are negatively correlated with milk production in lactating women. Overall, our results shed light on FUS as a negative regulator of milk production, providing a potential mechanism for the establishment of milk production from marsupial to eutherian mammals.

Corrigendum: The prospective outcome of the Monkeypox outbreak in 2022 and characterization of monkeypox disease immunobiology.

[This corrects the article DOI: 10.3389/fcimb.2023.1196699.].

ROR1-AS1 might promote in vivo and in vitro proliferation and invasion of cholangiocarcinoma cells.

Long non-coding RNAs (lncRNAs) play important roles in many pathophysiological processes, including cancer progression. Namely, lncRNA Receptor-tyrosine-kinase-like orphan receptor-1 antisense 1 (ROR1-AS1) is crucial for cancer occurrence and progression in organs such as the liver or bladder. However, its expression and role in cholangiocarcinoma (CCA) have not been thoroughly explored.Firstly, we assessed cell viability, proliferation, invasion, and migration using three cell lines (HuCCT-1, QBC399, and RBE) to explore the biological characteristics of ROR1-AS1 in CCA. Secondly, to determine the in vivo effect of ROR1-AS1 on tumor growth, ROR1-AS1 knockdown (KD) HuCCT-1 cells were subcutaneously injected into nude mice to evaluate tumor growth. Finally, we conducted a bioinformatic analysis to confirm the role of ROR1-AS1 in the prognosis and immunity of CCA.In this study, we found that lncRNA ROR1-AS1 was increased in CCA samples and patients with higher ROR1-AS1 expression had a shorter overall survival period. siRNA-mediated KD of ROR1-AS1 significantly reduced cell proliferation and inhibited the migration of CCA cells. In addition, ROR1-AS1 KD HuCCT-1 cells injected into nude mice grew slower than normal CCA cells.In summary, our results show that ROR1-AS1 can promote CCA progression and might serve as a new target for diagnosis and treatment of CCA.

The prospective outcome of the monkeypox outbreak in 2022 and characterization of monkeypox disease immunobiology.

A new threat to global health re-emerged with monkeypox's advent in early 2022. As of November 10, 2022, nearly 80,000 confirmed cases had been reported worldwide, with most of them coming from places where the disease is not common. There were 53 fatalities, with 40 occurring in areas that had never before recorded monkeypox and the remaining 13 appearing in the regions that had previously reported the disease. Preliminary genetic data suggest that the 2022 monkeypox virus is part of the West African clade; the virus can be transmitted from person to person through direct interaction with lesions during sexual activity. It is still unknown if monkeypox can be transmitted via sexual contact or, more particularly, through infected body fluids. This most recent epidemic's reservoir host, or principal carrier, is still a mystery. Rodents found in Africa can be the possible intermediate host. Instead, the CDC has confirmed that there are currently no particular treatments for monkeypox virus infection in 2022; however, antivirals already in the market that are successful against smallpox may mitigate the spread of monkeypox. To protect against the disease, the JYNNEOS (Imvamune or Imvanex) smallpox vaccine can be given. The spread of monkeypox can be slowed through measures such as post-exposure immunization, contact tracing, and improved case diagnosis and isolation. Final Thoughts: The latest monkeypox epidemic is a new hazard during the COVID-19 epidemic. The prevailing condition of the monkeypox epidemic along with coinfection with COVID-19 could pose a serious condition for clinicians that could lead to the global epidemic community in the form of coinfection.

ß-Glucan Induces Training Immunity to Promote Antiviral Activity by Activating TBK1.

Many studies have shown that ß-glucan induces a trained immune phenotype in innate immune cells to defend against bacterial and fungal infections. The specific mechanism involves cellular metabolism and epigenetic reprogramming. However, it is unclear whether ß-glucan plays a role in antiviral infection. Therefore, this study investigated the role of trained immunity induced by Candida albicans and ß-glucan in antiviral innate immunity. It showed that C. albicans and ß-glucan promoted the expression of interferon-ß (IFN-ß) and interleukin-6 (IL-6) in mouse macrophages triggered by viral infection. In addition, ß-glucan pretreatment attenuated the pathological damage induced by the virus in mouse lungs and promoted the expression of IFN-ß. Mechanistically, ß-glucan could promote the phosphorylation and ubiquitination of TANK Binding Kinase 1 (TBK1), a key protein of the innate immune pathway. These results suggest that ß-glucan can promote innate antiviral immunity, and this bioactive material may be a potential therapeutic target for antiviral treatment.

Senotherapeutics: An emerging approach to the treatment of viral infectious diseases in the elderly.

In the context of the global COVID-19 pandemic, the phenomenon that the elderly have higher morbidity and mortality is of great concern. Existing evidence suggests that senescence and viral infection interact with each other. Viral infection can lead to the aggravation of senescence through multiple pathways, while virus-induced senescence combined with existing senescence in the elderly aggravates the severity of viral infections and promotes excessive age-related inflammation and multiple organ damage or dysfunction, ultimately resulting in higher mortality. The underlying mechanisms may involve mitochondrial dysfunction, abnormal activation of the cGAS-STING pathway and NLRP3 inflammasome, the role of pre-activated macrophages and over-recruited immune cells, and accumulation of immune cells with trained immunity. Thus, senescence-targeted drugs were shown to have positive effects on the treatment of viral infectious diseases in the elderly, which has received great attention and extensive research. Therefore, this review focused on the relationship between senescence and viral infection, as well as the significance of senotherapeutics for the treatment of viral infectious diseases.

Analysis of Common Respiratory Infected Pathogens in 3100 Children after the Coronavirus Disease 2019 Pandemic.

OBJECTIVE: To investigate the epidemiological features in children after the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This study collected throat swabs and serum samples from hospitalized pediatric patients of Renmin Hospital of Wuhan University, Wuhan, Hubei province, China before and after the COVID-19 pandemic. Respiratory infected pathogens [adenovirus (ADV), influenza virus A/B (Flu A/B), parainfluenza virus 1/2/3 (PIV1/2/3), respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP), and Chlamydia pneumoniae (CP)] were detected. The pathogens, age, and gender were used to analyze the epidemiological features in children after the COVID-19 pandemic. RESULTS: The pathogen detection rate was significantly higher in females than in males (P<0.05), and the infection of PIV1 and MP was mainly manifested. After the COVID-19 pandemic, PIV1, PIV3, RSV, and MP had statistically different detection rates among the age groups (P<0.05), and was mainly detected in patients aged 0-6 years, 0-3 years, 0-3 years, and 1-6 years, respectively. When comparing before the COVID-19 pandemic, the total detection rate of common respiratory pathogens was lower (P<0.05). Except for the increase in the detection rate of PIV1 and CP, the infection rate of other pathogens had almost decreased. CONCLUSION: The prevention and control measures for the COVID-19 pandemic effectively changed the epidemiological features of common respiratory tract infectious diseases in pediatric children.

Video-assisted mediastinoscopic and laparoscopic transhiatal esophagectomy for esophageal cancer.

BACKGROUND: Mediastinoscopy was originally applied for lymph node biopsy and mediastinal tumor resection. Improved video imaging with spreadable working channels enabled mediastinoscopy for inspection and tissue biopsy in the superior mediastinum but it is rarely used in minimally invasive esophageal cancer surgery. In this prospective trial, the practicability and security of spreadable video-assisted mediastinoscopic combined with laparoscopic transhiatal esophagectomy (VAME) with video-assisted thoracoscopic esophagectomy (VATE) were compared. METHODS: A total of 200 eligible patients with esophageal squamous cell carcinoma were randomly divided into VAME or VATE groups. Early postoperative outcomes and lymph node dissection between the two groups were compared. RESULTS: The operation time was significantly shorter (164.3 ± 47.0 min vs. 265.4 ± 47.2 min, P < 0.001), the number of dissected lymph nodes was less (15.8 ± 4.5 vs. 20.3 ± 6.5, P < 0.001), and the intraoperative blood loss was also significantly reduced (94.7 ± 56.7 mL vs. 184.4 ± 65.2 mL, P < 0.001) in the VAME compared to the VATE group, respectively. The incidence of pneumonia was lower (7% vs. 29%; P < 0.001) and the length of hospital stay was shorter in the VAME group compared to the VATE group (18.0 ± 7.6 days vs. 23.2 ± 7.2, P < 0.001, respectively). The chyle leak incidence appeared to be lower in the VAME group but statistical significance was not reached (1% vs. 4%; P = 0.369). There were no differences in the incidence of anastomotic leakages and recurrent laryngeal nerve paralysis between the groups. No 30-day mortality occurred in any of the cases. CONCLUSION: VAME appears to be a practicable and secure method for esophagectomy but needs further proof of concept. CLINICAL REGISTRATION NUMBER: Registered at Chinese Clinical Trial Registry, ChiCTR1900022797.

Mapping knowledge landscapes and emerging trends of sonodynamic therapy: A bibliometric and visualized study.

Background: Ultrasound-triggered sonodynamic therapy (SDT), as a non-invasive approach, has attracted considerable attention in a wide variety of malignant tumors and other diseases. Over the past 2 decades, the number of scientific publications on SDT has increased rapidly. However, there is still a lack of one comprehensive report that summarizes the global research trends and knowledge landscapes in the field of SDT in detail. Thus, we performed a bibliometric analysis on SDT from 2000 to 2021 to track the current hotspots and highlight future directions. Methods: We collected publications on SDT research from the Web of Science Core Collection database. The annual number of publications and citations, major contributors, popular journals, international collaborations, co-cited references and co-occurrence keywords were analyzed and visualized with CiteSpace, VOSviewer, and R-bibliometrix. Results: A total of 701 publications were included. The annual publication output increased from 5 in 2000 to 175 in 2021, and the average growth rate was 18.4%. China was the most productive country with 463 documents (66.05%), and Harbin Medical University was the most prolific institution (N = 73). Ultrasound in Medicine and Biology published the most papers related to SDT. Materials Science, and Chemistry were the research areas receiving the most interest. All the keywords were divided into four different clusters including studies on mechanisms, studies on drug delivery and nanoparticles, studies on cancer therapy, as well as studies on ultrasound and sonosensitizers. In addition to nanomaterials-related studies including nanoparticles, mesoporous silica nanoparticles, nanosheets, liposomes, microbubble and TiO2 nanoparticle, the following research directions such as immunogenic cell death, metal-organic framework, photothermal therapy, hypoxia, tumor microenvironment, chemodynamic therapy, combination therapy, tumor resistance, intensity focused ultrasound, drug delivery, and Staphylococcus aureus also deserve further attention and may continue to explode in the future. Conclusion: SDT has a bright future in the field of cancer treatment, and nanomaterials have increasingly influenced the SDT field with the development of nano-technology. Overall, this comprehensive bibliometric study was the first attempt to analyze the field of SDT, which could provide valuable references for later researchers to better understand the global research trends, hotspots and frontiers in this domain.

Bevacizumab biosimilar LY01008 compared with bevacizumab (Avastin) as first-line treatment for Chinese patients with unresectable, metastatic, or recurrent non-squamous non-small-cell lung cancer: A multicenter, randomized, double-blinded, phase III trial.

BACKGROUND: Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC). METHODS: Stage IIIB-IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4-6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). RESULTS: Between December 15th , 2017, and May 15th , 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th , 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1-6) and median duration of treatment of 3.0 (range 0.0-5.1) months. ORR of response-evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80-1.04, within the prespecified equivalence margin of 0.75-1.33). Up to May 15th , 2020, with a median follow-up of 13.6 (range 0.8-28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1-year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. CONCLUSIONS: LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non-squamous NSCLC patients in the first-line setting.

Exosomal Circ-MEMO1 Promotes the Progression and Aerobic Glycolysis of Non-small Cell Lung Cancer Through Targeting MiR-101-3p/KRAS Axis.

Circular RNA mediator of cell motility 1 (circ-MEMO1) was identified as an oncogene in non-small cell lung cancer (NSCLC). Nevertheless, the working mechanism behind circ-MEMO1-mediated progression of NSCLC is barely known. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circ-MEMO1, microRNA-101-3p (miR-101-3p), and KRAS proto-oncogene, GTPase (KRAS). Cell proliferation and aerobic glycolysis were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and glycolysis detection kits. Flow cytometry was used to evaluate cell cycle progression and apoptosis of NSCLC cells. Western blot assay was used to measure the protein expression of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), KRAS, CD9, CD81, tumor susceptibility 101 (TSG101), and Golgi matrix protein 130 kDa (GM130). The target relationship between miR-101-3p and circ-MEMO1 or KRAS was predicted by StarBase software and confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pull down assay. In vivo tumor growth assay was conducted to assess the effect of circ-MEMO1 in vivo. Exosomes were isolated using the ExoQuick precipitation kit. Circ-MEMO1 was up-regulated in NSCLC, and high expression of circ-MEMO1 predicted poor prognosis in NSCLC patients. Circ-MEMO1 accelerated the proliferation, cell cycle progression, and glycolytic metabolism and inhibited the apoptosis of NSCLC cells. Circ-MEMO1 negatively regulated the expression of miR-101-3p through direct interaction, and si-circ-MEMO1-induced biological effects were attenuated by the introduction of anti-miR-101-3p. MiR-101-3p directly interacted with the 3' untranslated region (3' UTR) of KRAS messenger RNA (mRNA), and KRAS level was regulated by circ-MEMO1/miR-101-3p axis. Circ-MEMO1 silencing suppressed the NSCLC tumor growth in vivo. ROC curve analysis revealed that high expression of serum exosomal circ-MEMO1 (exo-circ-MEMO1) might be a valuable diagnostic marker for NSCLC. Circ-MEMO1 facilitated the progression and glycolysis of NSCLC through regulating miR-101-3p/KRAS axis.

Long Noncoding RNA CDKN2B-AS1 Facilitates Lung Cancer Development Through Regulating miR-378b/NR2C2.

AIM: Long noncoding RNA (lncRNA) have proved to be important regulators in various diseases. CDKN2B-AS1 was a newly identified tumor-related lncRNA, and previous studies have reported its function in laryngeal squamous cancer and osteosarcoma. However, the function and mechanism of lncRNA CDKN2B-AS1 in lung cancer are still unknown. METHODS: Cell proliferation, invasion, migration and apoptosis were detected via CCK-8, transwell assay and Western blot. Bioinformatics analysis was used to predict the potential target of CDKN2B-AS1. A rescue experiment was performed to identify the relationship between CDKN2B-AS1 and miR-378b. RESULTS: The expression of lncRNA CDKN2B-AS1 was significantly upregulated in lung cancer tissues and cell lines. Overexpression of CDKN2B-AS1 promoted cell proliferation, invasion and reduced cell apoptosis. Knockdown of CDKN2B-AS1 inhibited cell proliferation, invasion and increased cell apoptosis. Bioinformatics analysis predicted that miR-378b was the direct target. We also provided evidence that NR2C2 was the target of miR-378b. The expression of NR2C2 was significantly upregulated in lung cancer tissues and cell lines. The rescue experiment further confirmed the relationship between CDKN2B-AS1 and miR-378b. Overexpression of miR-378b completely reversed the function of CDKN2B-AS1. CONCLUSION: Taken together, our results comprehensively analyzed the function of CDKN2B-AS1 in lung cancer and provided a possible mechanism that CDKN2B-AS1 facilitates lung cancer development by regulating miR-378b and NR2C2. Thus, our study offers a potential therapeutic target for treating lung cancer.

High glucose contributes to the proliferation and migration of non-small cell lung cancer cells via GAS5-TRIB3 axis.

Despite the growing number of studies exhibited an association of diabetes mellitus (DM) and lung cancer progression, the concrete mechanism of DM aggravating lung cancer has not been elucidated. This study was to investigate whether and how high glucose (HG) contribute to the proliferation and migration of non-small cell lung cancer (NSCLC) cells in vitro. In the present study, we confirmed that HG promoted the proliferation and migration of NSCLC cells, and also induced an anti-apoptosis effect on NSCLC cells. Moreover, HG inhibited the expression of GAS5 in NSCLC cells but elevated the protein level of TRIB3. GAS5 overexpression promoted the degradation of TRIB3 protein by ubiquitination and inhibited the HG induced-proliferation, anti-apoptosis and migration of NSCLC cells. Importantly, TRIB3 overexpression reversed the effects of GAS5 on the HG-treated NSCLC cells. Taken together, down-regulated GAS5 by HG significantly enhanced the proliferation, anti-apoptosis and migration in NSCLC cells through TRIB3, thus promoting the carcinogenesis of NSCLC.

Sensitive detection of microRNAs with hairpin probe-based circular exponential amplification assay.

MicroRNAs (miRNAs) play important regulatory roles in a wide range of biological processes, and their aberrant expression is associated with cancer development and a variety of diseases. Here, we develop a simple, sensitive, and specific miRNA assay on the basis of circular exponential amplification in combination with the hairpin probes. The binding of target miRNA with a linear DNA template initiates the first strand displacement amplification (SDA) and generates the universal triggers which are complementary to the 3' protruding end of a hairpin probe. These universal triggers function not only as the primers to unfold the hairpin probes through an extension reaction, generating distinct fluorescence signals, but also as the amplification templates to initiate the second SDA reaction. Moreover, the second SDA reaction can release new triggers to initiate the above two consecutive SDA reactions, thus constituting a circular exponential amplification which enables the conversion of a small amount of miRNAs to a large number of universal triggers to unfold abundant hairpin probes. This hairpin probe-based circular exponential amplification assay exhibits high sensitivity with a detection limit of 3.80 × 10(-13) M and a detection range of 4 orders of magnitude. It can even discriminate single-nucleotide difference between miRNA family members and perform well in real sample analysis. Notably, in this assay, the long-stem hairpin probes are unfolded through an extension reaction rather than through a conventional hybridization reaction controlled by the thermodynamic equilibrium in the case of molecular beacons, making the design of hairpin probes very simple. This hairpin probe-based circular exponential amplification assay holds a great promise for further application in biomedical research and early clinical diagnosis.

Treatment of esophagogastric anastomotic leak with perianastomotic drain.

INTRODUCTION: The most efficient treatment of such anastomotic leaks after esophagectomy remains controversial. Our objective was to evaluate the effectiveness of perianastomotic drains in anastomotic leaks. METHODS: Five patients with intrathoracic anastomotic leaks had placement of perianastomotic drains through remanet esophagus and fitula into infected area. The other conservative methods of treatment were also chosen simultaneously. RESULTS: The perianastomotic drains were placed successfully in all five patients. None of the patients underwent rethoracotomy. They were all cured. The median period to clinical healing was 33 days. The median hospital stay after the perianastomotic drainage procedure was 37 days. CONCLUSION: This procedure proved to be safe and effective in the treatment of esophagogastric anastomotic leak with perianastomotic drain through fistula.