Research progress in the management of vascular disease with cannabidiol: a review.

The morbidity and mortality rates associated with vascular disease (VD) have been gradually increasing. Currently, the most common treatment for VD is surgery, with the progress in drug therapy remaining slow. Cannabidiol (CBD) is a natural extract of Cannabis sativa L. with sedative, analgesic, and nonaddictive properties. CBD binds to 56 cardiovascular-related receptors and exerts extensive regulatory effects on the cardiovascular system, making it a potential pharmacological agent for the management of VD. However, most CBD studies have focused on neurological and cardiac diseases, and research on the management of VD with CBD is still rare. In this review, we summarize the currently available data on CBD in the management of VD, addressing four aspects: the major molecular targets of CBD in VD management, pharmacokinetic properties, therapeutic effects of CBD on common VDs, and side effects. The findings indicate that CBD has anti-anxiety, anti-oxidation, and anti-inflammatory properties and can inhibit abnormal proliferation and apoptosis of vascular smooth muscle and endothelial cells; these effects suggest CBD as a therapeutic agent for atherosclerosis, stress-induced hypertension, diabetes-related vasculopathy, ischemia-reperfusion injury, and vascular damage caused by smoking and alcohol abuse. This study provides a theoretical basis for further research on CBD in the management of VD.

H3.3B controls aortic dissection progression by regulating vascular smooth muscle cells phenotypic transition and vascular inflammation.

Aortic dissection is a devastating cardiovascular disease with a high lethality. Histone variants maintain the genomic integrity and play important roles in development and diseases. However, the role of histone variants in aortic dissection has not been well identified. In the present study, H3f3b knockdown reduced the synthetic genes expression of VSMCs, while overexpressing H3f3b exacerbated the cellular immune response of VSMCs induced by inflammatory cytokines. Combined RNA-seq and ChIP-seq analyses revealed that histone variant H3.3B directly bound to the genes related to extracellular matrix, VSMC synthetic phenotype, cytokine responses and TGFß signaling pathway, and regulated their expressions. In addition, VSMC-specific H3f3b knockin aggravated aortic dissection development in mice, while H3f3b knockout significantly reduced the incidence of aortic dissection. In term of mechanisms, H3.3B regulated Spp1 and Ccl2 genes, inducing the apoptosis of VSMCs and recruiting macrophages. This study demonstrated the vital roles of H3.3B in phenotypic transition of VSMCs, loss of media VSMCs, and vascular inflammation in aortic dissection.

Murine model of elastase-induced proximal thoracic aortic aneurysm through a midline incision in the anterior neck.

Objective: This study was performed to develop a murine model of elastase-induced proximal thoracic aortic aneurysms (PTAAs). Methods: The ascending thoracic aorta and aortic arch of adult C57BL/6J male mice were exposed through a midline incision in the anterior neck, followed by peri-adventitial elastase or saline application. The maximal ascending thoracic aorta diameter was measured with high-resolution micro-ultrasound. Twenty-eight days after the operation, the aortas were harvested and analyzed by histopathological examination and qualitative polymerase chain reaction to determine the basic characteristics of the aneurysmal lesions. Results: Fourteen days after the operation, the dilation rate (mean ± standard error) in the 10-min elastase application group (n = 10, 71.44 ± 10.45%) or 5-min application group (n = 9, 42.67 ± 3.72%) were significantly higher than that in the saline application group (n = 9, 7.37 ± 0.94%, P < 0.001 for both). Histopathological examination revealed aortic wall thickening, degradation of elastin fibers, loss of smooth muscle cells, more vasa vasorum, enhanced extracellular matrix degradation, augmented collagen synthesis, upregulated apoptosis and proliferation capacity of smooth muscle cells, and increased macrophages and CD4+ T cells infiltration in the PTAA lesions. Qualitative analyses indicated higher expression of the proinflammatory markers, matrix metalloproteinase-2 and -9 as well as Collagen III, Collagen I in the PTAAs than in the controls. Conclusion: We established a novel in vivo mouse model of PTAAs through a midline incision in the anterior neck by peri-adventitial application of elastase. This model may facilitate research into the pathogenesis of PTAA formation and the treatment strategy for this devastating disease.

The synergistic mechanism of fibroblast growth factor 18 and integrin ß1 in rat abdominal aortic aneurysm repair.

BACKGROUND: Abdominal aortic aneurysms have a high mortality rate. While surgery is the preferred treatment method, the biological repair of abdominal aortic aneurysms is being increasingly studied. We performed cellular and animal experiments to investigate the simultaneous function and mechanism of fibroblast growth factor 18 and integrin ß1 in the biological repair of abdominal aortic aneurysms. METHODS: Endothelial and smooth muscle cells of rat arteries were used for the cellular experiments. Intracellular integrin ß1 expression was regulated through lentiviral transfection. Interventions with fibroblast growth factor 18 were determined according to the experimental protocol. Several methods were used to detect the expression of elastic fiber component proteins, cell proliferation, and migratory activity of endothelial and smooth muscle cells after different treatments. For animal experiments, abdominal aortic aneurysms were induced in rats by wrapping the abdominal aortae in sterile cotton balls soaked with CaCl2 solution. Fibroblast growth factor 18 was administered through tail vein injections. The local expression of integrin ß1 was regulated through lentiviral injections into the adventitia of the abdominal aortic aneurysms. The abdominal aortae were harvested for pathological examinations and tensile mechanical tests. RESULTS: The expression of integrin ß1 in endothelial and smooth muscle cells could be regulated effectively through lentiviral transfection. Animal and cellular experiments showed that fibroblast growth factor 18 + integrin ß1 could improve the expression of elastic fiber component proteins and enhance the migratory and proliferative activities of smooth muscle and endothelial cells. Moreover, animal experiments showed that fibroblast growth factor 18 + integrin ß1 could enhance the aortic integrity to withstand stretch of aortic aneurysm tissue. CONCLUSION: Fibroblast growth factor 18 + integrin ß1 improved the biological repair of abdominal aortic aneurysms in rats by increasing the expression of elastic proteins, improving the migratory and proliferative abilities of endothelial and smooth muscle cells, and improving aortic remodeling.

Three-dimensional evaluation of soft tissues in hyperdivergent skeletal class II females in Guangdong.

OBJECTIVES: To establish the three-dimensional facial soft tissue morphology of adolescent and adult females in the Guangdong population and to study the morphological characteristics of hyperdivergent skeletal class II females in Guangdong compared with that of normodivergent class I groups. MATERIALS AND METHODS: The 3dMDface system was used to capture face scans of 160 patients, including 45 normal and 35 hyperdivergent skeletal class II adolescents (aged 11-14 years old) and 45 normal and 35 hyperdivergent skeletal class II adults (aged 18-30 years old). Thirty-two soft tissue landmarks were mapped, and 21 linear, 10 angular and 17 ratio measurements were obtained by 3dMDvultus analysis software. Data were assessed with a t-test of two independent samples between the normal adolescent and adult groups and between the normal and hyperdivergent skeletal class II groups. RESULTS: The linear measurements of the Guangdong adult females were larger than those of the adolescents in both Class I and Class II groups. However, the angular and ratio measurements had no significant difference. The vertical linear measurements were higher and the sagittal and transverse linear measurements were smaller in the hyperdivergent class II group (p < 0.05). The soft tissue ANB angle, chin-lip angle, and mandibular angle were significantly larger and the soft tissue facial convexity angle and nasal convexity angle were significantly smaller in the hyperdivergent class II group (p < 0.05). Additionally, there were significant differences in the ratio measurements between the hyperdivergent class II groups and the control groups (p < 0.05). CONCLUSIONS: The three-dimensional facial morphology of Guangdong adolescent and adult females was acquired. The facial soft tissue measurements of the adults were higher in the three dimensions except for the facial convexity and proportional relationships which were similar, suggesting that the growth pattern remained the same. The three-dimensional facial soft tissue features of hyperdivergent skeletal class II were characterized by the terms "long, convex, and narrow". Three-dimensional facial measurements can reflect intrinsic hard tissue characteristics.

Dysregulation of interaction between LOXhigh fibroblast and smooth muscle cells contributes to the pathogenesis of aortic dissection.

Rationale: While cell-cell interaction plays a critical role in physiology and disease, a comprehensive understanding of its dynamics in vascular homeostasis and diseases is yet absent. Methods: Here, by use of single-cell RNA-sequencing and multi-color staining, we delineate the cellular composition and spatial characterization of human aorta with or without aortic dissection (AD). Results: Scrutinization of cell subtype alterations revealed significantly changed fibroblast (FB)-smooth muscle cell (SMC) interactions in AD. Of these cellular interactions, LOXhigh fibroblast (fibroblast subtype 2, FB2) in diseased state exerted the most pronounced effects on pathological deterioration of SMCs in AD. In addition, pharmacologically targeting the BMP (bone morphogenetic protein) signaling pathway effectively suppressed FB2 state transition and reduced AD incidence in mice. Finally, COL5A1 (collagen type V alpha 1 chain), one of the secreted proteins released from FB2, was significantly higher in the plasma of AD patients than in control patients, suggesting its potential use as a biomarker for AD diagnosis. Conclusions: Our work not only identified a pivotal role of a specific FB subtype in AD progression, but also shed light on cell interaction dynamics in vascular diseases.

Electromyographic features and efficacy of orofacial myofunctional treatment for skeletal anterior open bite in adolescents: an exploratory study.

BACKGROUND: Due to the multifactorial aetiology and unpredictable long-term stability, skeletal anterior open bite (SAOB) is one of the most intractable conditions for orthodontists. The abnormal orofacial myofunctional status (OMS) may be a major risk factor contributing to the development and relapse of SAOB. This study is aimed at evaluating the OMS and the efficacy of orofacial myofunctional therapy (OMT) alone for SAOB subjects. METHODS: Eighteen adolescents with SAOB (4 males, 14 females; age: 12-18 years) and eighteen adolescents with normal occlusion (2 males, 16 females; age: 12-18 years) were selected. The electromyographic activity (EMGA) associated with mastication and closed mouth state was measured. Lateral cephalography was used to evaluate craniofacial morphology. Wilcoxon signed rank tests and t-tests were performed to evaluate myofunctional and morphological differences. Pearson or Spearman correlation analysis was used to investigate the correlations between EMGA and morphological characteristics. SAOB subjects were given OMT for 3 months, and the EMGA was compared between before and after OMT. RESULTS: During rest, anterior temporalis activity (TAA) and mentalis muscle activity (MEA) increased in SAOB subjects, but TAA and masseter muscle activity (MMA) decreased in the intercuspal position (ICP); and upper orbicularis activity (UOA) and MEA significantly increased during lip sealing and swallowing (P < 0.05). Morphological evaluation revealed increases in the FMA, GoGn-SN, ANS-Me, N-Me, L1-MP, U6-PP, and L6-MP and decreases in the angle of the axis of the upper and lower central incisors and OB in SAOB subjects (P < 0.05). TAA, MMA and anterior digastric activity (DAA) in the ICP were negatively correlated with vertical height and positively correlated to incisor protrusion. MEA was positively correlated with vertical height and negatively correlated with incisor protrusion; and the UOA showed a similar correlation in ICP, during sealing lip and swallowing. After SAOB subjects received OMT, MEA during rest and TAA, MMA and DAA in the ICP increased, while UOA and MEA decreased (P < 0.05). CONCLUSION: SAOB subjects showed abnormal OMS features including aberrant swallowing patterns and weak masticatory muscles, which were interrelated with the craniofacial dysmorphology features including a greater anterior facial height and incisor protrusion. Furthermore, OMT contributes to OMS harmonization, indicating its therapeutic prospect in SAOB.

Association between Cystatin C and Peripheral Artery Disease in the Chinese Han Population.

BACKGROUND: Recent studies of the association between cystatin C and peripheral artery disease (PAD) have produced inconsistent results, and few studies have been conducted to investigate this association in the Chinese Han population. Therefore, we evaluated the relationship between cystatin C and PAD using Chinese data. METHODS: We performed a secondary analysis of the data from a previously published case-control study about PAD in our center. We examined the relationship between cystatin C and PAD by logistic regression models and subgroup and interaction analyses. We also constructed a propensity score-matched population by matching the conventional risk factors to further validate this association. In addition, we explored the relationship between cystatin C level and ankle-brachial index (ABI) strata (<0.4, ≥0.4) to shed light on a possible dose-dependent relationship between cystatin C levels and PAD severity. RESULTS: In total, 426 participants were included for evaluation. The mean serum cystatin C concentration was significantly lower in the control group than that in the case group (1.06 ± 0.19 mg/L vs. 1.24 ± 0.34 mg/L, P < 0.001). After adjustment for conventional risk factors, the risk of PAD was significantly higher in individuals with a cystatin C level of ≥1.25 mg/L. A 17% higher risk of PAD was associated with each 100-µg/L increase in the serum cystatin C level. Similar results were seen in the analyses of the propensity score-matched population comprising 164 participants. Furthermore, patients with an ABI <0.4 had higher cystatin C level than those with an ABI ≥0.4 (1.31 ± 0.05 mg/L vs. 1.18 ± 0.03 mg/L, P = 0.03). CONCLUSIONS: Our analysis indicated that an elevated cystatin C level is significantly associated with an increased risk of PAD in the Chinese Han population. Larger Chinese prospective cohort studies are needed to validate these findings.

A meta-analysis of locoregional anesthesia versus general anesthesia in endovascular repair of ruptured abdominal aortic aneurysm.

OBJECTIVE: To conduct a meta-analytic review of studies investigating the effect of the anesthesia modality on perioperative mortality in endovascular repair of ruptured abdominal aortic aneurysms (REVAR). METHODS: The present meta-analysis was performed in accordance with the PRISMA guidelines. Multiple electronic databases were comprehensively searched from database inception to January 2020. Eligible studies included cohort studies that reported the 30-day/in-hospital mortality rate or the multivariate adjusted odds ratio (OR) or hazard ratio of the mortality risk for patients who underwent emergency REVAR under locoregional anesthesia (LA) vs general anesthesia (GA). A random effects model was used to estimate the ORs by pooling the related data from individual studies. RESULTS: A total of eight studies were included in this analysis. The first meta-analysis of seven studies that reported the 30-day/in-hospital mortality with a total of 3116 patients (867 in the LA group and 2249 in the GA group) revealed that LA was associated with a lower 30-day/in-hospital mortality than GA (16.4% vs 25.4%; unadjusted OR, 0.47; 95% confidence interval [CI], 0.32-0.68). The second meta-analysis of three of these seven studies (including 586 patients in the LA group and 1945 in the GA group) that reported the perioperative variables revealed comparable baseline characteristics but a lower 30-day/in-hospital mortality in the LA group (unadjusted OR, 0.55; 95% CI, 0.42-0.71). The third meta-analysis of the adjusted ORs or hazard ratios that were reported from four studies (including 501 patients in the LA group and 1136 in the GA group) showed a similar trend (adjusted OR,0.37; 95% CI, 0.19-0.75). CONCLUSIONS: REVAR under LA is associated with a lower 30-day/in-hospital mortality than REVAR under GA. However, because the included studies may have had some observation bias, further randomized controlled trials are warranted to validate the present results.

The Association between Hyperhomocysteinemia and Thoracoabdominal Aortic Aneurysms in Chinese Population.

OBJECTIVE: To shed light on the association between hyperhomocysteinemia (HHcy) and thoracoabdominal aortic aneurysms (TAAAs). METHODS: From July 2013 to March 2017, we conducted a matched case-control study involving individuals who presented to the Chinese People's Liberation Army General Hospital and underwent thoracoabdominal magnetic resonance angiography or computed tomography angiography. A total of 73 patients with TAAAs were enrolled in the case group, and 219 sex-matched subjects without TAAAs were included in the control group. We then examined the relationship between HHcy and TAAAs by logistic regression models and subgroup as well as interaction analyses. RESULTS: Serum total homocysteine (tHcy) concentrations and the proportion of HHcy were significantly higher in the patients with TAAAs than in those without TAAAs (P < 0.001). Furthermore, the multivariate logistic regression models indicated that participants with HHcy had a 2.14-fold higher risk of TAAAs than those with a normal serum tHcy level (adjusted odds ratio (OR), 2.14; 95% confidence interval, 1.00-4.56). Similarly, each 1 µmol/L increase in the serum tHcy concentration was associated with a 4% higher risk of TAAAs (adjusted OR, 1.04; 95% confidence interval, 1.00-1.07). Subgroup analyses indicated that HHcy tended to be associated with a greater risk of TAAAs in all stratified subgroups (adjusted ORs > 1). Furthermore, the interaction analyses revealed no interactive role in the association between HHcy and TAAAs. CONCLUSIONS: The present case-control study suggests that HHcy is an independent risk factor for TAAAs. Larger prospective cohort studies are warranted to validate these findings.

Relationship between T stage and survival in distantly metastatic esophageal cancer: A STROBE-compliant study.

To shed light on the interaction between the American Joint Committee on Cancer (AJCC) T stage and M stage in the determination of the overall survival (OS) and cancer-specific survival (CSS) of esophageal carcinoma patients. Moreover, to confirm our hypothesis that tumors that metastasize to distant sites in the early T stage may reflect a more biologically aggressive disease compared with those that metastasize in more advanced T stages.We performed a retrospective cohort study with patients who were pathologically diagnosed with esophageal cancer between 2004 and 2014 in the surveillance epidemiology and end results (SEER) database. The primary study variables were the T and M stage, as well as their interaction terms. We performed a survival analysis of the interaction terms using unadjusted Kaplan-Meier methods and adjusted Cox proportional hazards models. Furthermore, we performed an exploratory analysis with stratification by histological type, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC).Data of 19,078 patients were retrieved from the SEER database. Unadjusted Kaplan-Meier curve indicated that patients with T2 and T3 stage had longer median OS and CSS (3 months and 4 months, respectively) than with T1 stage in distantly metastatic esophageal cancer (M1 stage). Multivariate analysis revealed a significant interaction between the T stage and M stage when determining the OS and CSS of esophageal cancer (P < .001). Using T1M0 as a reference, patients with T1M1 had significantly worse OS and CSS than those with T2M1 and T3M1 stage (P < .001). A similar pattern was also observed among patients with EAC and ESCC.Our analysis suggests that the T1 stage predicts worse survival compared with T2 and T3 stage in distantly metastatic esophageal cancer and might be a surrogate for biologically aggressive disease, indicating that those patients should receive more aggressive treatments. Our findings also encourage researchers to discover new genomic changes in this subset of tumors with the potential to uncover new prognostic markers or drug targets. Further researches on the association between T stage and survival in metastatic esophageal cancer are warranted to validate our findings.

A systematic review and meta-analysis on the efficacy and safety of traditional Chinese patent medicine Jinqi Jiangtang Tablet in the treatment of type 2 diabetes.

INTRODUCTION: At present, a large number of people in the world are suffering from type 2 diabetes (T2DM), so it is urgent to develop effective treatment measures of T2DM. In China, many clinical studies have shown that Jinqi Jiangtang Tablet (JQJTT), a traditional Chinese patent medicine (TCPM), has a good effect in the treatment of T2DM. This systematic review and meta-analysis is intended to assess the efficacy and safety of JQJTT plus conventional therapy in the treatment of T2DM. METHODS: Seven electronic databases were searched to include in eligible studies published from inception to May 24, 2018. Randomized controlled trials (RCTs) of JQJTT in combination with the conventional therapy versus conventional therapy alone or combined with placebo were included. The two reviewers independently conducted data extraction and quality assessment. For different variable types, the outcome measures were expressed as risk ratios (RRs) or mean differences (MDs). According to the value of I2, a fixed or random effect model was used for statistical analysis. RESULTS: Seventeen studies conducted in China were identified in this systematic review, which included 1,425 participants. The meta-analysis on the effective rate of the comparison groups showed a significant difference in favor of the JQJTT group (RR 1.34; 95%CI [1.02, 1.75]; p = 0.04). In addition, the results showed a statistically significant reduction in FBG (MD -0.85; 95%CI [-1.03, -0.68]; p < 0.00001), 2hPG (MD -1.95; 95%CI [-2.33, -1.56]; p < 0.00001), HbA1c (MD -0.76; 95%CI [-1.03, -0.49]; p < 0.00001), FINS (MD -3.05; 95%CI [-3.69, -2.42]; p < 0.00001), PINS (MD -10.22; 95%CI [-13.93, -6.50]; p < 0.00001), HOMA-IR (MD -1.11; 95%CI [-1.55, -0.68]; p < 0.00001), LDL-C (MD -0.37; 95%CI [-0.63, -0.11]; p = 0.006), TC (MD -0.46; 95%CI [-0.85, -0.08]; p = 0.02), TG (MD -0.34; 95%CI [-0.47, -0.20]; p < 0.00001) with JQJTT plus conventional therapy versus conventional therapy alone. There was no statistical difference between the two comparison groups in HDL-C, total incidence of adverse events and incidence of hypoglycemia. CONCLUSION: The available evidence indicates that JQJTT combined with conventional therapy for treating T2DM has a good performance in regulating glycolipid metabolism and improving insulin resistance. However, due to the limitations of this systematic review, the results should be interpreted with caution.

Identification of nine microRNAs as potential biomarkers for lung adenocarcinoma.

Lung cancer is a leading global cause of cancer-related death, and lung adenocarcinoma (LUAD) accounts for ~ 50% of lung cancer. Here, we screened for novel and specific biomarkers of LUAD by searching for differentially expressed mRNAs (DEmRNAs) and microRNAs (DEmiRNAs) in LUAD patient expression data within The Cancer Genome Atlas (TCGA). The identified optimal diagnostic miRNA biomarkers were used to establish classification models (including support vector machine, decision tree, and random forest) to distinguish between LUAD and adjacent tissues. We then predicted the targets of identified optimal diagnostic miRNA biomarkers, functionally annotated these target genes, and performed receiver operating characteristic curve analysis of the respective DEmiRNA biomarkers, their target DEmRNAs, and combinations of DEmiRNA biomarkers. We validated the expression of selected DEmiRNA biomarkers by quantitative real-time PCR (qRT-PCR). In all, we identified a total of 13 DEmiRNAs, 2301 DEmRNAs and 232 DEmiRNA-target DEmRNA pairs between LUAD and adjacent tissues and selected nine DEmiRNAs (hsa-mir-486-1, hsa-mir-486-2, hsa-mir-153, hsa-mir-210, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-577, and hsa-mir-4732) as optimal LUAD-specific biomarkers with great diagnostic value. The predicted targets of these nine DEmiRNAs were significantly enriched in transcriptional misregulation in cancer and central carbon metabolism. Our qRT-PCR results were generally consistent with our integrated analysis. In summary, our study identified nine DEmiRNAs that may serve as potential diagnostic biomarkers of LUAD. Functional annotation of their target DEmRNAs may provide information on their roles in LUAD.

Construction of a nomogram predicting the overall survival of patients with distantly metastatic non-small-cell lung cancer.

PURPOSE: This study aimed to establish a nomogram to predict the overall survival (OS) of the general non-small-cell lung cancer (NSCLC) patients with distant metastasis. PATIENTS AND METHODS: We investigated Surveillance, Epidemiology, and End Results database for NSCLC patients with distant metastasis diagnosed between 2010 and 2014. Statistically significant prognostic factors were identified using uni- and multivariable Cox regression analyses. A nomogram incorporating these prognostic factors was developed and evaluated by the Harrell's concordance index (C-index), calibration plots, and risk group stratifications. RESULTS: We finally included 18,209 patients for analysis. These patients were divided into two groups, 14,567 cases for the training cohort and 3,642 for the validation cohort. Marital status, sex, race, age, histology, T stage, N stage, histological differentiation, bone metastasis, brain metastasis, liver metastasis, with M1a disease, surgery of primary cancer, and chemotherapy were identified as the prognostic factors of the OS and integrated to construct the nomogram. The nomogram had a C-index of 0.704 (95% CI: 0.699-0.709) in the training set and 0.699 (95% CI: 0.689-0.709) in the validation set. The calibration curves for 1- and 2-year OS in the training and validation sets showed acceptable agreement between the predicted and observed survival. Also, the nomogram was capable of stratifying patients into different risk groups within the patients who presented with bone, liver, or brain metastasis, as well as in each T, N stage, respectively. CONCLUSION: A nomogram was established and validated to predict individual prognosis for the general patients with distantly metastatic NSCLC. Global prospective data with the latest TNM classification and more comprehensive prognostic factors are needed to improve this model.

Comparison of short-term outcomes between minimally invasive McKeown and Ivor Lewis esophagectomy for esophageal or junctional cancer: a systematic review and meta-analysis.

PURPOSE: Minimally invasive esophagectomy is increasingly performed for esophageal or gastroesophageal junctional cancer, with advantages of improved perioperative outcomes in comparison with open esophagectomy. McKeown and Ivor Lewis are widely used procedures of minimally invasive esophagectomy, and there have been controversies on which one is preferred for patients with resectable esophageal or junctional cancer. PATIENTS AND METHODS: This review was registered at the International Prospective Register of Systematic Reviews (number CRD42017075989). Studies in PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were thoroughly investigated. Eligible studies included prospective and retrospective studies evaluating short-term outcomes of minimally invasive McKeown esophagectomy (MIME) vs minimally invasive Ivor Lewis esophagectomy (MILE) in patients with resectable esophageal or junctional tumors. Main parameters included anastomotic leak and 30-day/in-hospital mortality. Overall incidence rates (ORs)/weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated by employing random-effects models. RESULTS: Fourteen studies containing 3,468 cases were included in this meta-analysis. Age, male sex, and American Joint Committee on Cancer (AJCC) stage between the 2 groups were not statistically different. MIME led to more blood loss, longer operating time, and longer hospital stay than MILE. MIME was associated with higher incidence of pulmonary complications (OR =1.96, 95% CI =1.28-3.00) as well as total anastomotic leak (OR =2.55, 95% CI =1.40-4.63), stricture (OR =2.07, 95% CI =1.05-4.07), and vocal cord injury/palsy (OR =5.62, 95% CI =3.46-9.14). In addition, the differences of R0 resection rate, number of lymph modes retrieved, blood transfusion rate, length of intensive care unit stay, incidence of cardiac arrhythmia, and Chyle leak between MIME and MILE were not statistically significant. Notably, incidence of severe anastomotic leak (OR =1.28, 95% CI =0.73-2.24) and 30-day/in-hospital mortality (OR =1.76, 95% CI =0.92-3.36) as well as 90-day mortality (OR =2.22, 95% CI =0.71-6.98) between the 2 procedures were also not significantly different. CONCLUSION: This study suggests that MIME and MILE are comparable with respect to clinical safety. MILE may be a better option when oncologically and clinically suitable. MIME is still a safe alternative procedure when clinically indicated. However, this evidence is at risk for bias; randomized controlled trials are needed to validate or correct our results.

Comparison of HIF1A­AS1 and HIF1A­AS2 in regulating HIF­1α and the osteogenic differentiation of PDLCs under hypoxia.

Hypoxia­inducible factor­1α (HIF­1α) is essential for regulating the osteogenic differentiation of periodontal ligament cells (PDLCs). The regulatory mechanism of HIF­1α transcription is still not clear. Recently, two long non­coding RNAs, HIF1A antisense RNA 1 (HIF1A­AS1) and HIF1A antisense RNA 2 (HIF1A­AS2), were found to regulate HIF­1α mRNA, but the regulatory mechanisms among HIF­1α, HIF1A­AS1 and HIF1A­AS2 have not been well studied. We hypothesized that HIF1A­AS1 and HIF1A­AS2 play important roles in the osteogenic differentiation of PDLCs by regulating HIF­1α. In the present study, we showed that expression levels of HIF1A­AS1, HIF1A­AS2, HIF­1α and osteogenic biomarkers were time­dependent under hypoxia. Even though both HIF1A­AS1 and HIF1A­AS2 were complementary to HIF­1α mRNA, only HIF1A­AS2 showed an inhibitory effect on HIF­1α in PDLCs. Moreover, HIF­1α had positive regulatory effects on HIF1A­AS1 and HIF1A­AS2. HIF­1α promoted the osteogenic differentiation of PDLCs, and HIF1A­AS2 had a negative effect on the osteogenic differentiation of PDLCs. Altogether, the present study revealed the complex relationships among HIF1A­AS1, HIF1A­AS2 and HIF­1α, as well as their roles in regulating the osteogenic differentiation of PDLCs. These findings provide a theoretical basis for promoting periodontal tissue regeneration and repair during orthodontic tooth movement.