[Unsupervised clustering analysis based on multidimensional features reveals distinct clinical characteristics and associated factors of different phenotypes in patients with chronic rhinosinusitis with nasal polyp].

Objective: To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis. Methods: The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software. Results: Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP. Conclusion: The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.

Comparison of two endoscope channel cleaning approaches to remove cyclic build-up biofilm.

INTRODUCTION: Biofilm contributes significantly to bacterial persistence in endoscope channels. Enhanced cleaning methods capable of removing biofilm from all endoscope channels are required to decrease infection risk to patients. This head-to-head study compared cyclic build-up biofilm removal of an automated endoscope channel cleaner (AECC) with standard manual cleaning according to instructions for use (IFU) in polytetrafluorethylene channels. METHODS: Cyclic build-up biofilm was grown in 1.4-mm (representing air/water and auxiliary channels) and 3.7-mm (representing suction/ biopsy channels) inner diameter polytetrafluorethylene channels. All channels were tested for residual total organic carbon, protein, and viable bacteria. Internationally recognized ISO 15883-5:2021 alert levels were used as cleaning benchmarks for protein (3 µg/cm2) and total organic carbon (6 µg/cm2). RESULTS: The automated cleaner significantly outperformed manual cleaning for all markers assessed (protein, total organic carbon, viable bacteria) in 1.4-mm and 3.7-mm channels representing air/water/auxiliary and suction/biopsy channels, respectively. Manual cleaning failed to remove biofilm from the air/water and auxiliary channels. According to the IFU, these channels are not brushed, suggesting a potential root cause for a portion of the numerous endoscopy-associated infections reported in the literature. CONCLUSION: AECC shows potential to deliver enhanced cleaning over current practice to all endoscope channels and may thereby address infection risk.

[Organ preservation and watch-and-wait strategy in esophageal cancer: a promising future].

The traditional treatment modalities for esophageal cancer include surgery, chemotherapy, and radiotherapy, each presenting its own limitations. With advancements in endoscopic techniques and the integration of immunotherapy, the feasibility and safety of organ preservation have significantly improved, offering patients improved survival and quality of life. The selection of patients suitable for organ preservation treatment demands ongoing exploration. Those selected for this approach require rigorous monitoring, with surgical intervention as a salvation for tumor progression or metastasis, though the timing of surgery remains a topic of debate. Organ preservation and watch-and-wait strategy may provide a more conservative treatment option, aiming to maximize quality of life.

[Application of "modified double pocket suture" pancreatoenterostomy in laparoscopic pancreatoduodenectomy].

Objective: The purpose of this study was to explore the value of the "improved double purse-string suture method" for pancreatojejunostomy in laparoscopic pancreaticoduodene-ctomy. Methods: The clinical data of 273 patients who underwent laparoscopic pancreaticoduode-nectomy in the Department of Hepatobiliary and Pancreatic Surgery of the First Hospital of Jilin University from January 2021 to May 2022 were retrospectively analyzed. According to the method of pancreaticoenteric anastomosis, the patients were divided into two groups: the "improved double purse-string suture method" group and the "Hong's one-stitch method" group. Results: The "improved double purse-string suture method" for pancreaticoenteric anastomosis was performed in a total of 189 patients, including 107 males and 82 females, with a mean age of (59.6±10.2) years. The "Hong's one-stitch method" group" was performed in a group of 84 patients, including 52 males and 32 females, with a mean age of (60.8±9.3) years.The results showed that the "improved double purse-string suture method" group had a lower incidence of postoperative pancreatic fistula (6.88% vs 8.33% for grade B fistula, and 1.58% vs 2.38% for grade C fistula) and a shorter anastomosis time [(25.25±4.73) min vs (25.76±6.71) min] than the "Hong's one-stitch method" group. There was no statistically significant difference between the two groups in terms of postoperative biliary fistula, abdominal bleeding, delayed gastric emptying, and other complications (P>0.05). Conclusion: The "improved double purse-string suture method" for pancreatojejunostomy is safe and feasible in laparoscopic pancreaticoduodenectomy.

KCNH2A561V Heterozygous Mutation Inhibits KCNH2 Protein Expression via The Activation of UPR Mediated by ATF6.

The potassium channel protein KCNH2 is encoded by KCNH2 gene, and there are more than 300 mutations of KCNH2. Unfolded protein response (UPR) is typically initiated in response to an accumulation of unfolded and/or misfolded proteins in the endoplasmic reticulum (ER). The present study aimed to explore the UPR process and the role of activating transcription factor 6 (ATF6) in the abnormal expression of potassium voltage-gated channel subfamily H member 2 (KCNH2)A561V. The wild-type (wt) KCNH2 and A561V mutant KCNH2 was constructed with his-tag. The 293 cells were used and divided into KCNH2wt+KCNH2A561V, KCNH2wt and KCNH2A561V groups. The expression levels of ATF6 and KCNH2 in different groups were detected by Western blotting, reverse transcription-quantitative PCR, immunofluorescence and immuno-coprecipitation assays. The protein types and abundance of immuno-coprecipitation samples were analyzed by mass spectrometry. The proteomic analysis of the mass spectrometry results was carried out by using the reactome database and GO (Gene Ontology) tool. The mRNA expression levels of KCNH2 and ATF6 in the KCNH2wt+KCNH2A561V group were higher compared with the KCNH2A561V group. However, the full-length protein expression of ATF6 was inhibited, indicating that ATF6 was highly activated and a substantial number of ATF6 was sheared in KCNH2wt+KCNH2A561V group compared with control group. Furthermore, A561V-KCNH2 mutation leading to the accumulation of the immature form of KCNH2 (135 kDa bands) in ER, resulting in the reduction of the ratio of 155 kDa/135 kDa. In addition, the abundance of UPR-related proteins in the KCNH2A561V group was higher compared with the KCNH2wt+KCNH2A561V group. The 'cysteine biosynthetic activity' of GO:0019344 process and the 'positive regulation of cytoplasmic translation activity' of GO:2000767 process in the KCNH2A561V group were higher compared with the KCNH2wt+KCNH2A561V group. Hence, co-expression of wild-type and A561V mutant KCNH2 in 293 cells activated the UPR process, which led to the inhibition of protein translation and synthesis, in turn inhibiting the expression of KCNH2. These results provided a theoretical basis for clinical treatment of Long QT syndrome.

[Expression profile of circular RNA in inflammatory response in human bronchial epithelial cells induced by carbon black nanoparticles].

Objective: To explore the toxic effect of carbon black nanoparticles on human bronchial epithelial cells, and identify the differentially expressed circular RNA based on the full transcriptome high-throughput sequencing, so as to provide evidence for the development of biomarkers exposed to carbon black nanoparticles and their application on epigenetic toxicology. Methods: In June 2020, 16 HBE cells were treated with carbon black nanoparticles at concentrations of 20, 40 and 80 µg/ml, and 16 HBE cells without any intervention were used as the control group. The cytotoxicity of carbon black nanoparticles was detected by CCK8 and LDH experiments. Real-time quantitative fluorescent PCR (qRT-PCR) and ELISA were used to detect the changes of interleukin-6 (IL-6) and interleukin-8 (IL-6, IL-8) mRNA and protein levels of carbon black nanoparticles with concentration gradient after 72 h exposure. Western blot analysis was conducted to detect the expression levels of toll-like receptor 4 (TLR4), phosphorylated nuclear factor-κB (P-NF-κB), apoptosis-related speckled protein (ASC) and Caspase-1 associated with nuclear factor-κB. According to high-throughput sequencing results, differentially expressed Circrnas were screened and identified by qRT-PCR, and those with stable differentially expressed circrnas and the strongest association with the NF-κB pathway were selected for ring performance identification. Results: After being exposed to carbon black nanoparticles for 72 h, the activity of 16HBE cells decreased significantly (P<0.05), and the release of lactate dehydrogenase increased significantly (P<0.05). Compared with control group, mRNA expression levels of IL-6 and IL-8, protein levels of IL-6 and IL-8 were increased, and protein levels of TLR4, p-NF-κB, ASC and Caspase-1 were significantly up-regulated in 16 HBE cells of different concentrations, with statistical significance (P<0.05). Compared with the control group, a total of 492 differentially expressed circular Rnas (|log2 FC|>1) were detected. Among the 5 differentially expressed (P<0.05) circular Rnas, circ_002642 was selected as the object of subsequent research on circular Rnas, affter 72 hours of exposure to 80 µg/ml CBNPs, 16HBE cells showed signlficantly higher expression of circ_002642 (P<0.05) . Conclusion: Carbon black nanoparticles can induce differentially expressed circular RNAs associated with inflammatory response in human bronchial epithelial cells.

[Outcomes of laryngotracheal reconstruction with anterior and posterior costal cartilage grafts in severe pediatric subglottic stenosis or laryngeal web].

Objective: To investigate outcomes of laryngotracheal reconstruction (LTR)with anterior and posterior costal cartilage grafts in severe pediatric subglottic stenosis (SGS) or laryngeal web (LW). Methods: A review of patients with severe subglottic stenosis or laryngeal web between January 2020 and January 2022 was performed. Demographic features including gender, age at diagnosis, age at surgery, etiology, airway support, and other comorbidities were collected preoperatively. Patients were evaluated in surgical site, breathing, swallowing, phonation and complications postoperatively.Descriptive analysis was used in this research. Results: Eight patients were included: six with grade Ⅲ SGS following Cotton-Myer grading scale, and two with type Ⅲ LW following Cohen's classification. All patients underwent LTR with anterior and posterior costal cartilage grafts. Five patients underwent single-stage LTR (ssLTR), and three patients underwent double-stage LTR (dsLTR). Seven out of eight patients were able to successfully extubate or decannulate with normal swallowing function; four patients had mild hoarseness, and three had moderate hoarseness. One patient failed in extubation, and underwent tracheotomy. Conclusions: LTR with anterior and posterior costal cartilage grafts is an effective and safe treatment for severe SGS or LW. Careful preoperative assessment of disease severity and overall medical status will help selection between ssLTR and dsLTR, thereby maximizing patient outcomes for both modalities.

Impact of Exercise and Cognitive Stimulation Therapy on Physical Function, Cognition and Muscle Mass in Pre-Frail Older Adults in the Primary Care Setting: A Cluster Randomized Controlled Trial.

OBJECTIVES: Multicomponent exercise program have shown to improve function and cognition in older adults but studies on pre-frail older adults in the primary care setting are limited. This study aimed i) to evaluate impact of 6 months exercise (Ex) versus complementary effect of 3 months of cognitive stimulation therapy (CST) to 6 months of Ex (Ex+CST) on physical function, muscle mass and cognition versus control group at 3, 6 and 12 months ii) inflammatory biomarkers such as Interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α). DESIGN: Cluster randomised control trial. SETTING AND INTERVENTION: Pre-frail older adults ≥ 65 years attending primary care clinic. Two intervention groups i) Ex 6 months ii) CST 3 months with Ex 6 months. MEASUREMENTS: At 0, 3, 6 and 12 months, questionnaires (on demographics, physical function, cognition, and depression) were administered and physical function assessment (gait speed, short physical performance battery (SPPB) test, handgrip strength, five times sit-to-stand (5x-STS)) was conducted. Muscle mass and its surrogates such as phase angle and body cell mass were measured using bioelectrical impedance analysis machine. Inflammatory biomarkers were measured at 0 and 3 months. RESULTS: Data from 190 participants was analysed at 3 months (111 control, 37 Ex and 41 Ex+CST). At 3 months, significant improvement in cognition was seen only in the Ex+CST group whereas improvements in depression, gait speed, SPPB and 5x-STS were seen in both the Ex and Ex+CST groups. At 6 months, the Ex+CST group improved in cognition and depression whereas improvement in frailty and muscle mass indices were seen in both the interventions groups. At 12 months, both the interventions groups had better perceived health, gait speed and less decline in muscle mass compared with control groups. Both the Ex and Ex+CST had significant association with TNF-α at 3 months (ß -2.71 (95% CI -4.80 - -0.62); p = 0.012 and ß -1.74 (95% CI -3.43 - -0.06); p = 0.043 respectively). CONCLUSION: Combined Ex+CST had significant improvement in cognition whereas the intervention groups improved in depression, physical function, muscle mass, frailty, perceived health and TNF-α levels. With growing evidence of the benefits of multicomponent interventions at primary care level, incorporating it into mainstream care with action plans on long-term sustainability and scalability should be a priority for every country.

[Prevention and treatment of postoperative complications of esophageal cancer].

Surgery is the primary treatment for esophageal cancer, but the postoperative complication rate remains high. Therefore, it is important to prevent and manage postoperative complications to improve prognosis. Common perioperative complications of esophageal cancer include anastomotic leakage, gastrointestinal tracheal fistula, chylothorax, and recurrent laryngeal nerve injury. Respiratory and circulatory system complications, such as pulmonary infection, are also quite common. These surgery-related complications are independent risk factors for cardiopulmonary complications. Complications, such as long-term anastomotic stenosis, gastroesophageal reflux, and malnutrition are also common after esophageal cancer surgery. By effectively reducing postoperative complications, the morbidity and mortality of patients can be reduced, and their quality of life can be improved.

Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies.

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

Circ_0124055 promotes the progression of thyroid cancer cells through the miR-486-3p/MTA1 axis.

BACKGROUND: Thyroid cancer is one of the malignancy cancers. CircRNA, a non-coding RNA, plays an important role in the development of cancer. The relationship and roles of circ_0124055, miR-486-3p and MTA1 in thyroid cancer have not been reported. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to analyze the RNA levels of circ_0124055, miR-486-3p and MTA1. Western blot was conducted to analyze the protein levels of MTA1, Epithelial cadherin (E-cadherin) and Neuro cadherin (N-cadherin). Subcellular localization assay was used to analyze circ_0124055 location in thyroid cancer cells. Colony formation assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay were carried out to analyze cell proliferation. Cell migration and invasion were analyzed by wound-healing assay and transwell assay. Flow cytometry assay was performed to investigate cell apoptosis. Dual-luciferase reporter assay and RIP assay were employed to analyze the interactions among circ_0124055, miR-486-3p and MTA1. Immunohistochemical (IHC) assay was performed to assess the expression of Ki67, MTA1 and E-cadherin in tumor tissues. Thyroid cancer tumor growth in vivo was evaluated by tumor xenograft mouse model assay. RESULTS: The expression of circ_0124055 was up-regulated in tumor tissues and cells. Knockdown of circ_0124055 could inhibit thyroid cancer cell proliferation, migration and invasion and promote cell apoptosis, accompanied by the dysregulation of E-cadherin and N-cadherin expression. Circ_0124055 could target miR-486-3p, and miR-486-3p could target MTA1. MiR-486-3p inhibitor could restore the effect of circ_0124055 knockdown in the progression of thyroid cancer. Moreover, MTA1 overexpression weakened the inhibitory effects of miR-486-3p mimics on the progression of thyroid cancer. Further, circ_0124055 could influence tumor growth in vivo. CONCLUSION: Circ_0124055 promoted the progression of thyroid cancer cells through the miR-486-3p /MTA1 axis.

Fetoscopic laser ablation for twin-to-twin transfusion syndrome in Malaysia: A 15-month retrospective cohort review from an emerging centre in South East Asia.

INTRODUCTION: The authors aim to review the early outcomes of fetostopic laser ablation (FLA) to improve outcomes for twin-to-twin transfusion syndrome (TTTS) in an emerging national centre in Malaysia. MATERIALS AND METHODS: This is a retrospective cohort study of 17 monochorionic diamniotic (MCDA) twin pregnancies with severe TTTS treated by FLA over 15 months in a single centre by a single operator after performing simulations. RESULT: The overall survival rate at day 28 after birth for at least one twin was 76% while the dual-twin survival was 64%. The survival rates at day 28 after birth for at least one twin for stages II, III and IV were 90% vs 40% vs 100% (p=0.054) while dual survival rates were 80% vs 0% vs 100% (p=0.05), respectively. The rate of miscarriage was higher with anterior placentation compared to posterior placentation (33% vs 18%, p=0.660). There was one case of recurrent TTTS and no twin anaemia-polycythaemia sequence post-FLA. The fetal medicine unit in Ipoh is the national centre in Malaysia which covers the whole country, including the western coast of the Borneo Island (Sabah, Sarawak and Labuan) accessible only by air travel. All three cases from Borneo Island had resolved TTTS after FLA and dual neonatal survival at day 28 after birth. CONCLUSION: This data from an emerging new fetoscopic laser centre in Malaysia indicates results consistent with the published international learning curve and within the limits of good clinical governance.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial.

BACKGROUND: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.

[Application of lateral upper arm free flap in the repair of postoperative defects of oral cancer].

Objective: To explore the clinical application and efficacy of lateral upper arm free flap (LUAFF) for one-stage repairing of soft tissue defect after oral cancer surgery. Methods: This article was a retrospective analysis of clinical data of 46 patients receiving treatment of one-stage repairing of soft tissue defect with LUAFF after oral cancer surgery in Hunan Cancer Hospital, from June 2019 to June 2021. Among these cases, 40 were males, and 6 were females. The patients' ages were from 23 to 64 years old. The clinical data of patients were reviewed and outcomes were evaluated. SPSS 23.0 software was used for statistical analysis. Results: In the LUAFF of 46 patients, flap area ranged from 5.0 cm×3.5 cm to 15.0 cm×7.0 cm; the mean pedicle length was 8.15±1.42 cm; the mean artery diameter was 1.20±0.41 mm (range, 1.5 to 2.5 mm); the mean diameter of the largest veins was 2.15±0.52 mm; and the median number of perforators was 2.6 (range, 1 to 4). All donor sites were closed primarily. Two cases had arterial anastomosis thrombosis, but their flaps were successfully saved with urgent re-anastomosis of the vessels. The overall flap survival rate was 93.5%(43/46), with flap necroses after operation in three cases. No patient received tracheotomy. The average hospital stay time of patients after operation was 9.4 days. The follow-up time was 6-24 months, elbow and wrist movements on the operative side were normal, and the upper limb muscle strength was not affected. Conclusions: LUAFF is a suitable choice for the repairs of small-moderate tissue defects in oral cancer surgery, with consistent perforators in the flap, simple harvest method, concealed donor-site scar, and high survival rate.

Retraction Note: Combination therapy with metformin and IL-12 to inhibit the growth of hepatic carcinoma by promoting apoptosis and autophagy in HepG2-bearing mice.

The article "Combination therapy with metformin and IL-12 to inhibit the growth of hepatic carcinoma by promoting apoptosis and autophagy in HepG2-bearing mice, by Z. Jin, B.-X. Jia, L.-D. Tan, Q.-M. Chen, Y.-H. Liu, published in Eur Rev Med Pharmacol Sci 2020; 24 (23): 12368-12379-DOI: 10.26355/eurrev_202012_24031-PMID: 33336757" has been retracted by the authors as they cannot ensure the reliability of the manuscript due to inaccuracies in the conclusions and in the experiment (the cell migration and invasion assay along with the cell cycle arrest assay are missing). The Publisher apologizes for any inconvenience this may cause https://www.europeanreview.org/article/24031.

[Outcomes of surgical management of typeâ ¢ laryngotracheal clefts: anterior laryngofissure approach and posterior cartilage graft laryngotracheoplasty].

Objective: Our aim of this study is to describe the outcomes of a series of patients who underwent cleft repair and posterior cartilage grafts laryngotracheoplasty (LTP) from anterior midline cervical approach for type Ⅲ laryngotracheoesophageal clefts (LETC). Methods: A review of patients with type Ⅲ LETC between May 2017 and December 2021 was performed. Demographic features including gender, age at surgery, weight, airway support, feeding status, and airway and other comorbidities were collected preoperatively. Patients were evaluated in breathing, swallowing and phonation postoperatively. The developmental status and morbidities were recorded. Results: Five patients who underwent cleft repair and posterior cartilage grafts LTP from anterior midline cervical approach were included. All patients survived and thrived postoperatively. At last follow-up, 3 patients were able to successfully extubate with acceptable voice, and 2 patients were tracheostomied. Four patients were able to be fed orally without aspiration, and one patient needed to be fed by thick food. Conclusion: The combination of cleft repair and posterior cartilage grafts LTP from anterior midline cervical approach is an effective and safe treatment for type Ⅲ LETC.

How inflationary gravitons affect gravitational radiation.

We include the single graviton loop contribution to the linearized Einstein equation. Explicit results are obtained for one loop corrections to the propagation of gravitational radiation. Although suppressed by a minuscule loop-counting parameter, these corrections are enhanced by the square of the number of inflationary [Formula: see text]-foldings. One consequence is that perturbation theory breaks down for a very long epoch of primordial inflation. Another consequence is that the one loop correction to the tensor power spectrum might be observable, in the far future, after the full development of 21 cm cosmology. This article is part of the theme issue 'The future of mathematical cosmology, Volume 2'.

Fed-batch anaerobic digestion of raw and pretreated hazelnut skin over long-term operation.

This study provided important insights on the anaerobic digestion (AD) of hazelnut skin (HS) by operating a fed-batch AD reactor over 240 days and focusing on several factors impacting the process in the long term. An efficient reactor configuration was proposed to increase the substrate load while reducing the solid retention time during the fed-batch AD of HS. Raw HS produced maximally 19.29 mL CH4/g VSadd/d. Polyphenols accumulated in the reactor and the use of NaOH to adjust the pH likely inhibited AD. Maceration and methanol-organosolv pretreatments were, thus, used to remove polyphenols from HS (i.e. 82 and 97%, respectively) and improve HS biodegradation. Additionally, organosolv pretreatment removed 9% of the lignin. The organosolv-pretreated HS showed an increment in methane potential of 21%, while macerated HS produced less methane than the raw substrate, probably due to the loss of non-structural sugars during maceration.

[Advantages and disadvantages of transthoracic approach for adenocarcinoma of the esophagogastric junction].

Adenocarcinoma of the esophaogastric junction (AEG) has anatomical characteristics of spanning two organs and anatomical sites. Thoracic surgery and gastrointestinal surgery aim at the safe resection margin of esophagus, the scope of lower mediastinal lymph node dissection and whether transthoracic surgery will increase complications. However, there are great differences and controversies in the surgical approach, surgical method, lymph node dissection and extent of resection of AEG. For Siewert II AEG via abdominal mediastinal approach, due to the limitation of exposure and the difficulty of operation, it is difficult to acquire a satisfactory proximal resection margin, and very difficult to dissect the inferior mediastinal lymph nodes. The transthoracic approach can provide adequate exposure, reduce the difficulty of operation, obtain satisfactory resection margin of esophagus and allow lower mediastinal lymph node dissection, which may bring better prognosis. Although transthoracic approach may increase the incidence of pulmonary infection, the standard development of thoracoscopic technology will overcome the disadvantage of transthoracic approach for Siewert II AEG.