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Background: Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACR) are the standard treatments for esophageal squamous cell carcinoma (ESCC). However, the 5-year overall survival (OS) rate is still far from satisfactory. In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in Henan Cancer Hospital. ICIs combined with NAC may usher in a new era and may benefit locally advanced, resectable ESCC patients., Methods: A two-arm phase III trial was launched in April 2020 in Henan Cancer Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future., Discussion: This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment., Trial Registration: NCT04280822 (https://www.clinicaltrials.gov/ct2/show/NCT04280822). Registered title: "A Phase III, Randomized Controlled Study of Neo-adjuvant Toripalimab (JS001) in Combination with Chemotherapy versus Neo-adjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma". Version 1.0/Nov. 21, 2019., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5404). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: The accuracy of clinical N staging of esophageal squamous cell carcinoma is suboptimal. As an important station of lymph node metastasis, station C201 (right recurrent laryngeal nerve nodes) has rarely been evaluated alone. We aimed to explore an effective way to evaluate the right recurrent laryngeal nerve nodes in thoracic esophageal squamous cell carcinoma., Methods: We retrospectively analyzed 628 thoracic esophageal squamous cell carcinoma patients who underwent radical resection without neoadjuvant therapy from two Chinese cancer centers. The diameter of the short axis of the largest right recurrent laryngeal nerve node (DC201) was measured on contrast-enhanced multi-slice computed tomography (MSCT). Right recurrent laryngeal nerve nodes were examined by postoperative pathologic results. The receiver operating characteristic (ROC) curve was generated to assess the diagnostic capabilities of DC201 to determine the right recurrent laryngeal nerve nodes status., Results: ROC curve analysis revealed that the optimal cut-off point of DC201 was 6 mm, with an area under curve (AUC), sensitivity, specificity, and Youden index of 0.896, 71.9%, 88.8%, and 0.607 respectively. When the cut-off point of DC201 was set to 10 mm, sensitivity, specificity and the Youden index were 14.1%, 99.6% and 0.137 respectively. Among 128 patients with right recurrent laryngeal nerve node metastasis, 71 and 108 patients had the largest right recurrent laryngeal nerve node located above the suprasternal notch level and in the tracheoesophageal groove respectively., Conclusions: When DC201 ≥6.0 mm instead of DC201 ≥10 mm was used to dictate the right recurrent laryngeal nerve nodes metastasis, contrast-enhanced MSCT could evaluate the status of right recurrent laryngeal nerve nodes with high sensitivity and specificity. The largest right recurrent laryngeal nerve nodes were mainly located in the tracheoesophageal groove and/or above the suprasternal notch., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-774). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background: Cervical sagittal imbalance compromises health-related quality of life and can lead to myriad incapacitating symptoms through compression of the spinal cord. Questions regarding which parameters play primary roles in the progression of cervical sagittal imbalance and which might be compensatory factors remain unanswered., Methods: This study enrolled 246 asymptomatic volunteers from July 2016 to June 2018. After demographic and radiologic parameters were measured, the data were analyzed using correlation coefficient test and multiple regression analysis. A predictive equation was assessed with variance analysis, residual analysis, collinearity analysis, and a paired t test., Results: Average values are as follows: orbital tilt, 64 ± 6°; orbital slope (OS), 15 ± 6°; C0-C2 lordosis (C0C2), 28 ± 8°; cervical lordosis (CL), 5 ± 11°; C2-C7 sagittal vertical axis (C2C7SVA), 15 ± 8 mm; T1 slope (TS), 17 ± 6°; thoracic inlet angle, 69 ± 8°; thoracic kyphosis, 34 ± 9°; lumbar lordosis, 50 ± 10°; sacral slope, 38 ± 7°; pelvic index, 48 ± 9°; sagittal vertical axis, 10 ± 19 mm. Correlations of C2C7SVA were observed with body mass index (BMI), OS, C0C2, CL, and TS. The validated predictive equation was: C2C7SVA = 0.38 × BMI - 0.73 × OS + 0.73 × C0C2 + 0.15 × CL + 0.18 × TS - 6.53., Conclusions: BMI, OS, C0C2, CL, and TS were primary influencers in the progression of cervical sagittal imbalance and established a predictive equation of asymptomatic population, which can provide clinical advice and remind surgeons of the primary influencers of reconstructive surgery for better prognoses., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: We sought to acquire the whole sagittal spine parameters and investigated the acceptable chin-brow vertical angle (CBVA) for neutral position radiography in an asymptomatic Chinese population., Methods: The parameters measured in 257 asymptomatic volunteers included CBVA, occipital slope, orbital tilt, occipital incidence, C0-C2 Cobb angle, C2-C7 Cobb angle, C1-C7 Cobb angle, C2-C7 sagittal vertical axis and absolute rotation angle, cervical tilt, cranial tilt, T1 slope, and thoracic kyphosis, and others. We used Pearson correlation analyses to find relationships between CBVA and other variables. The subjects were divided into 5 groups according to the CBVA percentile: group A, 0%-20% CBVA; group B, 20%-40% CBVA; group C, 40%-60% CBVA; group D, 60%-80% CBVA; and group E, 80%-100% CBVA. We used analysis of variance to analyze differences among the 5 groups., Results: Orbital tilt, Occipital incidence, C1-C7 Cobb angle, C2-C7 sagittal vertical axis, and cranial tilt all increased with increasing CBVA (P < 0.001). The occipital slope, C2-C7 Cobb angle, C2-C7 absolute rotation angle, cervical tilt, T1 slope, and thoracic kyphosis decreased with decreasing CBVA (P < 0.05). No correlations between other sagittal parameters and the CBVA were found. A slight deviation was found in groups B-D, with a greater deviation in groups A, C, and E., Conclusions: An acceptable range of -1.5° to 5.8° is recommended for the CBVA for cervical radiography in the neutral position. When spinal surgeons evaluate the cervical plane, the effects of the CBVA deviation on cervical curvature must be considered., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Neuromuscular scoliosis (NS) is a complicated spinal disorder, and it could be treated through posterior-only approach (POA) or combined anterior-posterior approach (APA), which one is better and how to choose the surgical tactic is still in controversy. So comparing POA with APA parameters in the treatment of NS is meaningful., Methods: Database of PubMed, Embase and Cochrane Library was systematically searched, and the studies, which focus on the comparisons of POA and APA in the treatment of NS, were included. The meta-analysis was performed by RevMan 5.3., Results: Seven retrospective studies with 602 patients were included in meta-analysis. In previous analysis, statistically significant differences were observed in the major parameters between APA and POA. However, the results of subgroup meta-analysis, which focused on the correction angle and loss angle to eliminate the influence of different preoperative angles, were tend to no difference between two groups, except loss angle of scoliosis (MD, 6.4; 95% CI - 0.19 to 13) and correction angle of pelvic obliquity (MD, - 3.44; 95% CI - 6.71 to - 0.17)., Conclusions: Our meta-analysis suggested that POA was similar to APA in the correction of scoliosis in coronal and sagittal planes. However, APA had advantages in the correction of pelvic obliquity and decreasing the loss of angle between postoperation and follow-up in main scoliosis, whereas POA had advantages in operative time, blood loss, duration of hospital stay and complications., Level of Evidence: Level II. These slides can be retrieved under Electronic Supplementary Material.

The HLA gene complex on human chromosome 6 is one of the most polymorphic regions in the human genome and contributes in large part to the diversity of the immune system. Accurate typing of HLA genes with short-read sequencing data has historically been difficult due to the sequence similarity between the polymorphic alleles. Here, we introduce an algorithm, xHLA, that iteratively refines the mapping results at the amino acid level to achieve 99-100% four-digit typing accuracy for both class I and II HLA genes, taking only [Formula: see text]3 min to process a 30× whole-genome BAM file on a desktop computer., Competing Interests: Conflict of interest statement: C.X., Z.X.Y., M.W., J.P., T.L., E.F.K., W.H.B., K.B., A.T., S.H., S.B., Y.T., and J.C.V. are employees of Human Longevity Inc. There is a patent pending on the technique presented in this work.

Introduction: The incidence of lumbar disc degeneration disease has increased in recent years. Lumbar interbody fusion using two unilateral pedicle screws and a translaminar facet screw fixation has advantages of minimal invasiveness and lower costs compared with the traditional methods. Moreover, a method guided by a three-dimensional (3D) navigation template may help us improve the surgical accuracy and the success rate. This is the first randomised study using a 3D navigation template to guide a unilateral lumbar pedicle screw with contralateral translaminar facet screw fixation., Methods and Analysis: Patients who meet the criteria of the surgery will be randomly divided into experimental groups and control groups by a computer-generated randomisation schedule. We will preoperatively design an individual 3D navigation template using CATIA software and MeditoolCreate. The following primary outcomes will be collected: screw angles compared with the optimal screw trajectories in 3D digital images, length of the wound incision, operative time, intraoperative blood loss and complications. The following secondary outcomes will be collected: visual analogue scale (VAS) for back pain, VAS for leg pain and the Oswestry Disability Index. These parameters will be evaluated on day 1 and then 3, 6, 12 and 24 months postoperatively., Ethics and Dissemination: The study has been reviewed and approved by the institutional ethics review board of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University. The results will be presented at scientific communities and peer-reviewed journals., Trial Registration Number: ChiCTR-IDR-17010466., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Transpedicular transdiscal screw fixation is an alternative technique used in lumbar spine fixation; however, it requires an accurate screw trajectory. The aim of this study is to design a novel 3D-printed custom drill guide and investigate its accuracy to guide the trajectory of transpedicular transdiscal (TPTD) lumbar screw fixation. Dicom images of thirty lumbar functional segment units (FSU, two segments) of L1-L4 were acquired from the PACS system in our hospital (patients who underwent a CT scan for other abdomen diseases and had normal spine anatomy) and imported into reverse design software for three-dimensional reconstructions. Images were used to print the 3D lumbar models and were imported into CAD software to design an optimal TPTD screw trajectory and a matched custom drill guide. After both the 3D printed FSU models and 3D-printed custom drill guide were prepared, the TPTD screws will be guided with a 3D-printed custom drill guide and introduced into the 3D printed FSU models. No significant statistical difference in screw trajectory angles was observed between the digital model and the 3D-printed model ( P  > 0.05). Our present study found that, with the help of CAD software, it is feasible to design a TPTD screw custom drill guide that could guide the accurate TPTD screw trajectory on 3D-printed lumbar models., Competing Interests: All authors declare that there are no conflict of interest.

Background: Impaired admission glucose (AG) is thought to significantly increase the risk of both early and late death with ST-segment elevation myocardial infarction (STEMI), especially for non-diabetic patients. However, several earlier studies contradict these relationships. Through our meta-analysis, we aimed to evaluate such a relation between impaired AG, the risk of death and STEMI., Methods: We accessed PubMed, EMBASE, Web of Science, and the Cochrane Library and systematically searched their databases to identify all related prospective cohort studies. The relative risks (RRs) with their 95% confidence interval (CI) were pooled quantitatively., Results: The pooled, unadjusted relative risks of early outcome events indicated that patients who had glucose concentrations ≥ the range of 6.1-11.1 mmol/L, had a 4.38-fold (95% CI, 3.23-5.94) higher early mortality. For late outcome events, the pooled unadjusted RR indicated patients who had glucose concentrations ≥ the range 7.8-11.1 mmol/L, and had a 2.69-fold (95% CI, 2.16-3.34) higher late mortality based on full participants, whereas patients had a 1.65-fold (95% CI, 1.33-2.04) higher late mortality based on based on in-hospital or 30-day survivors., Conclusions: In conclusion, the present meta-analysis demonstrated that impaired admission glucose may be an effective prognostic marker for significantly increased risk of early death. Regarding the long-term outcomes based on full population or early survival, high admission glucose also has a distinct but poorer prognostic impact on long-term mortality than early mortality., Key Words: Admission glucose • Meta-analysis • Myocardial infarction • Non-diabetic.

Batch methods were deployed to study the removal of phosphate by calcite in an open-system. Results showed that: (1) The pre-equilibrium process of calcite in open system could be achieved within 24 hours (2) The kinetic results showed that, at initial concentration of 0.5 mg · L⁻¹, the phosphate removal was almost completed within 10 hours of the first phase. The observation may be attributed to surface adsorption. At initial concentration of 2.5 mg · L⁻¹, the phosphate removal was mainly carried out by the precipitation of phosphate at later stage of the process; (3) At initial concentration of ≤ 2.5 mg · L⁻¹ setting 10 h as reaction time, the phosphate removal process was described well by the Langmuir model. It is hypothesized that surface adsorption was the principal removal way of phosphate; (4) With the addition of phthalate, at initial concentration of < 2.5 mg · L⁻¹, the phosphate removal rate experienced a small decrease. That was because phosphate was mainly removed by surface adsorption, and thus, phthalate was a competitor to phosphate for the same adsorption site. The phosphate removal rate increased a little at initial concentration of > 2.5 mg · L⁻¹, this was because the phosphate precipitation was reinforced by the increase of calcium concentration, which was caused by phthalate addition.

The batch sorption methods were deployed to study the sorpti of p-phthalate on calcite in open-system. Results show that: (1) The o-phthalate sorption reached the equilibrium within 3 hours. Both pseudo first-order and pseudo second-order models described the kinetic characteristics well; (2) The o-phthalate sorption rate decreased with pH (7. 7-9.7). This phenomenon was due to the competition effect of HCO3- and CO(3)2-, and the electrostatic effect on the surface; (3) The o-phthalate sorption rate also decreased with the increase in ionic strength. This was due to the rise in concentration of HCO3- and CO(3)2- induced by salt effect; (4) Compared with m-phthalate and p-phthalate, o-phthalate sorption rate was much higher due to the proximity of its two carboxyl groups which easily formed a chelate ring of surface complex. By studying the factors that influence o-phthalate sorption onto calcite, the sorption mechanism can be well understood. This mechanism can be applied in the removal of o-phthalate from the environment.

Background: Impaired admission glucose (AG) is considered to significantly increase risk on both early and late death of the patients with ST-segment elevation myocardial infarction (STEMI), especially for non-diabetic patients; however, some reports contradict the relationship. We therefore conducted a meta-analysis to clarify this issue., Material/methods: PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched to identify all related prospective cohort studies. The relative risks (RR) with their 95% confidence interval (CI) were pooled quantitatively., Results: The pooled RR of early outcome events indicated patients with glucose concentrations ≥6.1-11.1 mmol/L had a 4.38-fold (95% CI, 3.23-5.94) higher early mortality. The pooled RR of late outcome events indicated that the patients with glucose concentrations ≥7.8-11.1 mmol/L had a 1.65-fold (95% CI, 1.33-2.04) higher late mortality based on in-hospital or 30-day survivors., Conclusions: High AG may be a helpful prognostic marker of significantly increased risk on early death in non-diabetic patients with STEMI, and has an explicit but prognostic adverse impact on long-term mortality but not early mortality in these patients.

Objective: Polymorphisms in XPG were considered to contribute to the clinical outcome of patients receiving platinum drug chemotherapy. We investigated the impact of several potential SNPs of XPG on the efficacy of platinum-based chemotherapy in NSCLC patients., Methods: A total of 433 patients were consecutively selected between Nov. 2006 and Dec. 2007, and were followed-up up to Nov. 2011. The genotyping of six SNPs (rs2296147, rs751402, rs873601, rs4150375, rs17655 and rs2094258) were genotyped using the Taqman real-time PCR method with a 7900 HT sequence detector system., Results: Patients carrying CT+TT genotype of rs2296147 had a significantly longer median PFS (17.5 months) and OS (26.8 months) than CC genotype. Hazard ratio (HR) for PFS and OS in patients with CT+TT genotype of rs2296147 was respectively 0.73(0.51-0.97) and 0.66(0.48-0.99) when compare CC genotype, respectively. Similarly, patients with rs2094258 AG+GG genotype had a longer median progression time (18.4 months) and overall survival time (27.3 months) when compared with those with AA genotype, and HRs(95% CI) for PFS and OS were 0.44(0.34-0.78) and 0.51(0.39-0.82), respectively., Conclusions: Our study suggests rs2296147 CT+TT and rs2094258 AG+GG genotypes contribute to the better survival of NSCLC. Our study provides significant information on role of prognostic value of XPG SNPs, and detecting of XPG could be used as predictive markers toward individualizing NSCLC treatment strategies.

P53 is probably the most important tumor suppressor known. Over the years, information about this gene has increased dramatically. We have built a comprehensive knowledgebase of p53, which aims to facilitate wet-lab biologists to formulate their experiments and new-comers to learn whatever they need about the gene and bioinformaticians to make new discoveries through data analysis. Using the information curated, including mutation information, transcription factors, transcriptional targets, and single nucleotide polymorphisms, we have performed extensive bioinformatics analysis, and made several new discoveries about p53. We have identified point missense mutations that are over-represented in cancers, but lack of functional studies. By assessing the capability of six p53 transcriptional targets' tag SNPs selected from HapMap to capture SNPs obtained from National Institute of Environmental Health Sciences (NIEHS) Environmental Genome project and vice versa, we conclude that NIEHS data is a better source for tagSNP selections of these genes in future association studies. Analysis of microRNA regulation in the transcriptional network of the p53 gene reveals potentially important regulatory relationships between oncogenic microRNAs and transcription factors of p53. By mapping transcription factors of p53 to pathways involved in cell cycle and apoptosis, we have identified distinctive transcriptional controls of p53 in these two physiological states.