A approach of gastric conduit via the anterior of pulmonary hilum route during minimally invasive McKeown esophagectomy.

BACKGROUND: The gastric conduit is the most commonly used replacement organ for reconstruction after minimally invasive McKeown esophagectomy. Although the optimal route of gastric conduit remains controversial, the posterior mediastinal route is physiologically preferable but is not without disadvantages. Here, we report the safety and efficacy of a method of gastric conduit reconstruction via the anterior of the pulmonary hilum route. METHODS: We have used the anterior of the pulmonary hilum route since 2021. This procedure involves pulling the gastric conduit up through a substernal tunnel between the right thoracic cavity and the abdominal cavity and passing it into the neck via the anterior of the pulmonary hilum route. In this retrospective study, we compared the clinical outcomes between 20 patients who underwent this procedure and 20 patients who underwent the posterior mediastinal route from 2021 to 2022. RESULTS: No mortality was reported in either group. No significant differences were observed between the two groups in duration of surgery, blood loss, incidence of postoperative complications, and postoperative hospital stay. As a result of the anterior of the pulmonary hilum route, the primary tumor bed and lymph node drainage area were effectively bypassed, which facilitates postoperative adjuvant radiotherapy or chemoradiotherapy. The distance of the gastric conduit accompanying the airway was significantly shorter in the anterior of the pulmonary hilum route group. CONCLUSIONS: Our method is considered to be a safe and useful technique for the reconstruction of gastric conduit.

Carotid artery direct access for intracranial stenting of a stroke patient with an aberrant left common carotid artery and right aorta.

A right aortic arch is present in 0.1% of the population and can occur in isolation or be associated with congenital heart disease.1 Moreover, the most common form of right aortic arch in adults is associated with an aberrant left subclavian artery.1 An aberrant left common carotid artery that originated from the ascending aorta with the right aorta is very rare. In this situation, carotid direct access was considered to avoid access challenge due to a large curve from the ascending aorta to the left common carotid artery.2 3 Here we demonstrate carotid artery direct access for intracranial stenting of a stroke patient with aberrant left common carotid artery and right aorta. Manual compression with a long time under general anesthesia to avoid post-procedural puncture site hematoma is recommended (video 1).neurintsurg;jnis-2023-020535v1/V1F1V1Video 1 Carotid artery direct access.

FOXK1 regulates malignant progression and radiosensitivity through direct transcriptional activation of CDC25A and CDK4 in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a serious malignancy with poor prognosis, necessitating identification of oncogenic mechanisms for novel therapeutic strategies. Recent studies have highlighted the significance of the transcription factor forkhead box K1 (FOXK1) in diverse biological processes and carcinogenesis of multiple malignancies, including ESCC. However, the molecular pathways underlying FOXK1's role in ESCC progression are not fully understood, and its potential role in radiosensitivity remains unclear. Here, we aimed to elucidate the function of FOXK1 in ESCC and explore the underlying mechanisms. Elevated FOXK1 expression levels were found in ESCC cells and tissues, positively correlated with TNM stage, invasion depth, and lymph node metastasis. FOXK1 markedly enhanced the proliferative, migratory and invasive capacities of ESCC cells. Furthermore, silencing FOXK1 resulted in heightened radiosensitivity by impeding DNA damage repair, inducing G1 arrest, and promoting apoptosis. Subsequent studies demonstrated that FOXK1 directly bound to the promoter regions of CDC25A and CDK4, thereby activating their transcription in ESCC cells. Moreover, the biological effects mediated by FOXK1 overexpression could be reversed by knockdown of either CDC25A or CDK4. Collectively, FOXK1, along with its downstream target genes CDC25A and CDK4, may serve as a promising set of therapeutic and radiosensitizing targets for ESCC.

Reciprocal regulation of LINC00941 and SOX2 promotes progression of esophageal squamous cell carcinoma.

LINC00941 is a novel long noncoding RNA (lncRNA) and emerging as an important factor in cancer development. However, the exact function and relative regulatory mechanism of LINC00941 in carcinogenesis of esophageal squamous cell carcinoma (ESCC) remain to be further clarified. The present study was to investigate the expression level, functions, and mechanisms of LINC00941 in ESCC tumorigenesis. LINC00941 was significantly upregulated in ESCC, and upregulated LINC00941 was correlated with dismal patient outcomes. LINC00941 functioned as an oncogene by promoting cells proliferation, stemness, migration, and invasion in ESCC. In terms of mechanisms, SOX2 could bind directly to the promoter region of LINC00941 and activate its transcription. In turn, LINC00941 upregulated SOX2 through interacting with interleukin enhancer binding factor 2 (ILF2) and Y-box binding protein 1 (YBX1) at the transcriptional and post-transcriptional levels. LINC00941 recruited ILF2 and YBX1 to the promoter region of SOX2, leading to upregulation of the transcription of SOX2. Moreover, LINC00941 could promote the binding ability of ILF2 and YBX1 on mRNA of SOX2 and further stabilize SOX2 mRNA. Therefore, LINC00941 contributed to the malignant behaviors of ESCC cells via the unrestricted increase in SOX2 expression. In conclusion, our data indicate that LINC00941 exacerbates ESCC progression through forming a LINC00941-ILF2/YBX1-SOX2 positive feedback loop, and LINC00941 may be a promising prognostic and therapeutic target for ESCC.

KTN1-AS1, a SOX2-mediated lncRNA, activates epithelial-mesenchymal transition process in esophageal squamous cell carcinoma.

Kinectin 1 antisense RNA 1 (KTN1-AS1), a long non-coding RNA (lncRNA), has been proved to have tumor-promoting properties and its expression is enhanced in several human tumors. However, the role of KTN1-AS1 in the pathogenesis of esophageal squamous cell carcinoma (ESCC) remains unknown. This study aimed to investigate the expression status, functional roles, and molecular mechanisms of KTN1-AS1 in the development of ESCC. Considerable upregulation of KTN1-AS1 was confirmed in esophageal cancer cells and ESCC tissues and its expression was associated with TNM stage, pathological differentiation, and lymph node metastasis. SOX2 directly activated transcription of KTN1-AS1, and overexpression of KTN1-AS1 facilitated ESCC cells proliferation and invasion in vitro and in vivo. Furthermore, KTN1-AS1 could bind to retinoblastoma binding protein 4 (RBBP4) in the nucleus and enhanced its binding with histone deacetylase 1 (HDAC1), thereby activating the epithelial-mesenchymal transition (EMT) process through downregulating E-cadherin expression at the epigenetic level. In conclusion, KTN1-AS1, induced by SOX2, acts as a tumor-promoting gene and may serve as a potential therapeutic and prognostic biomarker for ESCC.

The clinical prognostic value of long noncoding RNA HAND2-AS1 in cancer patients: A study based on meta-analysis and TCGA data (PRISMA).

BACKGROUND: The heart and neural crest derivatives expressed 2 antisense RNA 1 (HAND2-AS1) is a novel long noncoding RNA aberrantly expressed in human malignancies. We aimed to analyze the available data to evaluate the clinical prognostic significance of HAND2-AS1 in tumors. METHODS: In this meta-analysis, electronic databases, including PubMed Cochrane Library, EMBASE, Medline, Web of Science, CNKI, and Wanfang, were searched from their inception up to December 1, 2021. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the relationship of HAND2-AS1expression level with prognosis and clinicopathological features in cancer patients. The publication bias was identified by Begg's test, and the sensitivity analysis was also performed. RESULTS: A total of 10 articles with 615 patients were included in the present meta-analysis. The combined results revealed that low expression of HAND2-AS1 was associated with poor overall survival (OS) (HR = 0.48, 95% CI: 0.36-0.64, P < .001) in a variety of cancers. In addition, the decrease in HAND2-AS1 expression was also correlated with poor differentiation (OR = 4.36, 95% CI: 2.15-8.87, P < .001) and lymph node metastasis (OR = 0.26, 95% CI: 0.13-0.54, P < .001). The cancer genome atlas (TCGA) dataset further demonstrated that low expression of HAND2-AS1 was associated with poor OS and disease-free survival. CONCLUSIONS: Our results of this meta-analysis indicated that HAND2-AS1 may be a prognostic marker and even a therapeutic target for human cancer.

E2F1-activated NRSN2 promotes esophageal squamous cell carcinoma progression through AKT/mTOR pathway.

BACKGROUND: Neurensin­2 (NRSN2) has been reported to act as an oncogene in several types of human cancer. However, the molecular mechanism of NRSN2 in esophageal squamous cell carcinoma (ESCC) remains to be elucidated. METHODS: The mRNA expression levels of NRSN2 in ESCC tissues and cell lines were evaluated by quantitative real-time PCR (qRT-PCR). The protein expression levels of NRSN2 in ESCC tissues were measured by Immunohistochemical (IHC) method. Luciferase reporter and chromatin immunoprecipitation assays were conducted to confirm the upstream transcription factor of NRSN2. Loss- and gain-function assays were conducted to evaluate the effects of NRSN2 on ESCC cells proliferation, migration, and invasion. The function of NRSN2 was validated in vivo using tumor xenografts. The relationship between NRSN2 and AKT/mTOR pathway were confirmed by western blot assay. RESULTS: The expression level of NRSN2 was increased in ESCC tissues and cell lines. High expression level of NRSN2 was correlated with depth of invasion, lymph node metastasis, TNM stage, and poor prognosis of ESCC patients. NRSN2 was transcribed by E2F1. Knockdown of NRSN2 significantly inhibited ESCC cells proliferation, migration, and invasion, whereas NRSN2 overexpression showed reverse phenotypes. Overexpression of NRSN2 also enhanced ESCC tumorigenicity in vivo. Furthermore, the E2F1/NRSN2 axis promoted proliferation, migration, and invasion of ESCC cells by activating the AKT/mTOR pathway. CONCLUSION: NRSN2 is a direct transcriptional target of E2F1 to promote tumor progression in ESCC. NRSN2 may be a diagnostic biomarker or treatment target for ESCC.

Long non-coding RNA NRSN2-AS1, transcribed by SOX2, promotes progression of esophageal squamous cell carcinoma by regulating the ubiquitin-degradation of PGK1.

Aberrant expression of long non-coding RNAs (lncRNAs) plays pivotal roles in tumorigenesis of human malignant cancers, including esophageal squamous cell carcinoma (ESCC). However, the specific role of lncRNA NRSN2-AS1 in ESCC has not been investigated. Our analysis of clinical data revealed that NRSN2-AS1 was upregulated in ESCC tissues and negatively correlated with patient survival. Luciferase reporter assays and chromatin immunoprecipitation assays demonstrated that NRSN2-AS1 is transcribed by SOX2. In vitro functional experiments showed that NRSN2-AS1 can promote ESCC cell proliferation, migration, and invasion. Furthermore, NRSN2-AS1-binding proteins were detected using RNA pull-down assays and mass spectrometry. Mechanistically, NRSN2-AS1 can bind to phosphoglycerate kinase 1 (PGK1) and upregulate its protein levels by inhibiting its ubiquitination. Knockdown of PGK1 in part abolished the NRSN2-AS1 overexpression-induced effects on ESCC cell proliferation, migration, invasion, and epithelial­mesenchymal transition (EMT). Thus, NRSN2-AS1 may be a diagnostic biomarker or treatment target for ESCC.

Development and validation of a nomogram for prediction of cervical lymph node metastasis in middle and lower thoracic esophageal squamous cell carcinoma.

BACKGROUND: Estimates of cervical lymph node (LN) metastasis in patients with middle and lower thoracic esophageal squamous cell carcinoma (ESCC) are important. A nomogram is a useful tool for individualized prediction. METHODS: A total of 235 patients were enrolled in this study. Univariate and multivariate analyses were performed to screen for independent risk factors and construct a nomogram to predict the risk of cervical LN metastasis. The nomogram performance was assessed by discrimination, calibration, and clinical use. RESULTS: Totally, four independent predictors, including the maximum diameter of tumor, paraesophageal lymph node status, recurrent laryngeal nerve lymph node status, and the CT-reported cervical LN status, were enrolled in the nomogram. The AUC of the nomogram model in the training and validation dataset were 0.833 (95% CI 0.762-0.905), 0.808 (95% CI 0.696-0.920), respectively. The calibration curve demonstrated a strong consistency between nomogram and clinical findings in predicting cervical LN metastasis. Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSION: We developed a nomogram that could be conveniently used to predict the individualized risk of cervical LN metastasis in patients with middle and lower thoracic ESCC.

Stability of Weld Pool and Elimination of Weld Defects in Aluminum Alloy Plasma Arc Keyhole Welding at Continuously Varying Positions.

Mathematical statistics were used to study the stability of weld pool and the elimination of weld defects in aluminum alloy plasma arc keyhole welding at continuously varying positions. In the mathematical model, the mass transfer position and spatial welding position were taken as the input, and the shape of the welded joints (symmetry/deviation) was taken as the output. The results showed that the fitted curves of the front, back, and average deviations of the weld seam were all similar to the actual curves. According to the optimum results obtained in the experiment and the mathematical models, the mass transfer position only needs to be adjusted once (near to 30°) during the continuously varying positions, from vertical-up to horizontal welding. A breakthrough from fixed environmental variables to dynamic environmental variables in the process control of the keyhole weld pool was realized, which enabled the Al-alloy keyhole weld pool to resist the disturbance caused by gravity during variable position welding. The deviation of the welded joints of the whole plate was smaller than 0.5 mm, and the mechanical properties of the weld reached at least 85% compared to those of the base material, thus meeting the requirements of Al-alloy welding.

FOXD3 suppresses epithelial-mesenchymal transition through direct transcriptional promotion of SMAD7 in esophageal squamous cell carcinoma.

The transcription factor forkhead box D3 (FOXD3) is an important member of the FOX family, which can maintain the pluripotent properties of cell clusters, neural crest, and trophoblastic progenitor cells in vivo. It has been shown that FOXD3 could affect proliferation, migration, and angiogenesis of various tumors and its deletion and overexpression in organisms will undoubtedly have important influence on the change of cell fate and the occurrence of tumors. However, the underlying functions and molecular mechanisms of FOXD3 in esophageal squamous cell carcinoma (ESCC) have not been fully clarified. According to the present study, the expression levels and functional roles of FOXD3 were investigated, and its prognostic value and molecular mechanisms in tumorigenesis and progression of ESCC were clarified. The expression level of FOXD3 was significantly downregulated in ESCC tissues and cell lines, and correlated with gender, family history of upper gastrointestinal cancer, TNM stage, depth of invasion, lymph node metastasis, and ESCC patients' survival. Moreover, FOXD3 inhibited cells migration and invasion as well as participated in TGF-ß1 induced epithelial-mesenchymal transition process. Furthermore, a positive correlation between FOXD3 and SMAD family member 7 (SMAD7) was explored in ESCC. FOXD3 could directly bind to promoter regions of SMAD7 gene, leading to transcriptional promotion of SMAD7 in human esophageal cancer cells. Taken together, FOXD3 may play a tumor suppressor role in ESCC and may be applied as a new therapeutic target and prognostic marker for ESCC.

Case report of a 72-year-old man with diaphragmatic hernia and thoracic gastropericardial fistula after esophagectomy for 18 years.

BACKGROUND: Both diaphragmatic hernia and thoracic gastropericardial fistula rarely occur simultaneously in patients with radical esophagectomy. CASE PRESENTATION: A 72-year-old man presented to our hospital with 1 day of nausea, vomiting and acute left chest pain. He had radical esophagectomy (Sweet approach) for esophageal cancer 18 years ago. Computed tomography (CT) of the chest revealed diaphragmatic hernias and air collection within the pericardial space. While an operation of diaphragmatic hernia repair was decisively performed to prevent further serious complications, unusually, a thoracic gastropericardial fistula was also found unusually. CONCLUSION: Diaphragmatic hernia and thoracic gastropericardial fistula may occasionally coexist in patients with esophagectomy. Upper GI radiograph with a water-soluble contrast agent is a better diagnostic tool than CT in visualizing the fistula.

Effect of chronic cyclic heat stress on the intestinal morphology, oxidative status and cecal bacterial communities in broilers.

The objective of this study was to examine the effects of chronic cyclic heat stress (HS) on the intestinal morphology, oxidative stress and cecal bacterial communities of broilers. One-day-old Arbor Acres (AA) male broilers (n = 100) were acclimated for 3 weeks and then randomly allocated into two groups, normal control (NC) group (22 ± 1 °C, 24 h/day) and HS group (32 ± 1 °C, 10 h/day lasted for 2 weeks). At 35 d of age, intestinal segments (duodenum, jejunum and ileum) and cecal digesta were collected for detection. HS affected intestinal morphology, inducing epithelial cell abscission, inflammatory cell infiltration, and lamina propria edema. Compared with the NC group, HS significantly decreased (P < 0.01) villus height (VH) and the VH-to-crypt depth (CD) ratio (VCR), increased (P < 0.05) CD in the duodenum and ileum, but had no effect on the VH in the jejunum. Moreover, HS induced oxidative stress with antioxidant enzymes activity decreasing (P < 0.05) while malondialdehyde (MDA) content increasing (P < 0.05) in small intestine. Pearson's correlation analysis indicated that MDA content was negatively correlated with VH (P < 0.05). The result of 16S rRNA sequencing showed that HS exposure impacted cecal microbiota alpha diversity (phylogenetic diversity whole-tree index) and beta diversity. Based on principal coordinate analysis (PCoA) plots for weighted UniFrac metrics and unweighted pair group method with arithmetic mean (UPGMA), there were 8 discriminative features at the genus level (linear discriminant analysis score > 2). Parabacteroides, Saccharimonas, Romboutsia and Weissella were reduced, while Anaerofustis, Pseudonocardia, Rikenella and Tyzzerella were enriched in heat-stressed broilers. Collectively, these results indicated that chronic cyclic HS induced oxidative stress that caused damage to intestinal villus-crypt structures, and then altered the cecal microflora profile.

A Primary Study of Variable Polarity Plasma Arc Welding Using a Pulsed Plasma Gas.

A process variant of variable polarity plasma arc welding (VPPAW), that is, the pulsed plasma gas VPPAW process, was developed. The pulsed plasma gas was transmitted into the variable polarity plasma arc through a high-frequency solenoid valve to modify the output of the plasma arc. The collection of arc electrical characteristics, arc shapes, and weld formation from VPPAW, double-pulsed VPPAW (DP-VPPAW), and pulsed plasma gas VPPAW (PPG-VPPAW) was carried out to examine if the pulsed plasma gas was able to play a positive role in improving the stability and quality of the VPPAW process. The arc voltage shows that the pulsed plasma gas had a greater influence on the electrode positive polarity voltage. The lower the plasma gas frequency was, the lower the arc voltage fluctuation frequency was and the greater the arc voltage fluctuation amplitude was. From the arc image, it could be observed that the arc core length had a short decrease during the general rising trend after plasma gas was turned on. The arc core width only had a slight change due to the restriction of the torch orifice. Compared with pulsed current wave, the pulsed plasma gas could better enhance the fluidity of the molten pool to reduce porosity during aluminum keyhole welding.

Ca2+ protect zebrafish embryos from water acidification.

Ionizable strategies are routinely used to enhance the solubility and dissolution rates of various pharmaceuticals. These chemicals may directly affect aquatic environment once discharged from factories, hospitals or livestock farms. Here, we assessed the potential side effect of tetracyclines (TCs) on the development of zebrafish embryos. Tetracycline hydrochloride decreased water pH from 6.4 to 4.4 at 30 mg/L. Acidified water exceeded the tolerance of zebrafish embryos in pure water during the early ten hours post fertilization (hpf). Interestingly, we found that Ca2+ in the embryo medium could increase the tolerance of embryos to acidified water. Furthermore, we found that the protection of Ca2+ was not due to the formation of TCs-Ca2+ complexes under acidic condition, based on spectral analysis. Meanwhile we showed that exogenous addition of Ca2+ could inhibit the accumulation of Ca2+ from the cytoplasm to the surface of embryos. These results may shed light on the strategies for protecting aquatic animals from acidic environments.

Macrolides induce severe cardiotoxicity and developmental toxicity in zebrafish embryos.

Macrolide antibiotics (MALs) are widely used for both human and animal health. Most MALs and their metabolites transfer into aquatic organisms and environment resulting in violent consequences. Previous studies show that MALs cause cardiotoxicity in humans and mammals. However, the potential risk of these chemicals in aquatic organisms remains unclear. Here, we used zebrafish embryos as a model to evaluate the toxicity of MALs. Zebrafish embryos were exposed to four typical MALs including azithromycin (AZM), clarithromycin (CLR), tilmicosin (TMS) and tylosin (TYL) to study their cardiotoxicity. The heart rate of zebrafish embryos showed similar biphasic distribution in the presence of four MALs at 2 days post-fertilization (dpf). The heart rate increased significantly at low levels of MALs while decreased obviously at high levels. Subsequently, TMS was chose to study its acute toxicity and developmental toxicity, which caused pericardial edema and spinal curvature in zebrafish embryos at 4 dpf. Furthermore, we found that TMS triggered oxidative stress, with decreased SOD activities and increased MDA contents. Lastly, apoptosis was observed in zebrafish embryos under TMS treatment, with up-regulation of apoptosis associated genes such as p53, bcl 2, bax, caspase 3 and caspase 9, confirmed by increased protein expression based on Western blot analysis. Taken together, these data indicate that MALs can cause serious toxicity in the development of zebrafish. Great caution should be taken due to the huge consumption of MALs for food animal production and treatments with TMS for infections in aquaculture.

Enhanced hypertension prevalence in non-Han Chinese minorities from Xinjiang Province, China.

Hypertension and its risk factors have been thoroughly investigated in multiple population studies, but little is known about Chinese minorities. In this study, we examined the association of hypertension prevalence with its risk factors in Han and non-Han minorities from Xinjiang Province, China, who have distinct lifestyles. A total of 9551 Han and non-Han Chinese (Han 83.9%, non-Han 16.1%) 17-81-years old participated in this clinical survey and anthropometric screening. Physical examination was performed on each participant, including measurement of systolic and diastolic blood pressure and body mass index (BMI). The prevalence of hypertension in non-Hans was found to be significantly greater than in Hans, in both men (39.92% vs. 28.55%, P<0.001) and women (19.49% vs. 10.29%, P<0.001) among the 36-55-year old age group. BMI was also found to be significantly higher in non-Hans than Hans in men (BMI: 26.54+/-3.23 vs. 24.82+/-2.77 kgm(-2), P<0.001) and women (BMI: 26.92+/-3.20 vs. 24.19+/-3.16 kgm(-2), P<0.001) in the same age group, but not in those <36-years old. Although Han women had normal weights or were slightly overweight (age >36, BMI=22.25-24.19 kgm(-2)), non-Han women from the same age group were found to be severely overweight (ages 36-55, BMI=24.94 kgm(-2), ages >56, BMI=26.92 kgm(-2)). A strong association between increased BMI and hypertension was shown in all ethnic and gender groups. The prevalence of hypertension in overweight (BMI> or =24 kgm(-2)) and obese (BMI> or =28 kgm(-2)), aged (36-81), male, and non-Han participants was significantly greater than in lean (BMI <24 kgm(-2)), young (17-35), female Hans, after adjustment for these variables in a multivariate logistic regression analysis (P<0.001). A high prevalence of hypertension in overweight and obese elderly non-Han men suggests that BMI, age, sex and race are important risk factors for hypertension in this Chinese population.