Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial.

BACKGROUND: Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects. METHODS: An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14-20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21-27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period. RESULTS: The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52-218.71%) and 287.54% (263.28-314.04%) for tegoprazan and 423.23% (382.57-468.22%) and 385.61% (354.62-419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44-90.45%) and 110.30% (102.74-118.41%) for clarithromycin, 126.25% (114.73-138.93%) and 146.94% (135.33-159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73-82.60%) and 94.34% (87.94-101.20%) for amoxicillin, and 158.43% (125.43-200.11%) and 183.63% (156.42-215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages. CONCLUSION: The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability. CLINICAL TRIALS REGISTRATION: CTR20230643.

Accurate location describe and management of lymph node recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma：a retrospective cohort study.

BACKGROUND: Describe the accurate locations of lymph node recurrence LNR of Chinese patients with postoperative thoracic esophageal squamous cell carcinoma (ESCC) is essential for determining the need for further surveillance protocols and treatments. We aimed to evaluate the patterns of postoperative ESCC and its current risk stratification with LNR. METHODS: This population-based cohort study included a retrospective review of the medical records and image material of patients with ESCC who underwent LNR after radical surgery between January 2013 and September 2022, with a median follow-up time of 5.71 years. Clinical features were extracted from these records, and survival analysis was performed. The primary endpoint was the accurate location and range of LNR according to the nomenclature of the Japanese Society for Esophageal Diseases. The second endpoints was to explore the related factors of recurrence range (RR) and overall survival (OS) . RESULTS: A total of 3268 lymph node regions were recurrence from 1129 patients, with a mean of 2.89 regions per patient. No.104, 106 and 107 was the most common recurrence of thoracic ESCC with an LNR rate higher than 15%. In upper thoracic ESCC, No.105 was a common recurrence site and abdominal lymph node recurrence was rare. In lower thoracic ESCC, retroperitoneal lymph node was a unique regions (15.4%). Anastomotic recurrence is an important recurrence pattern in patients with postoperative esophageal cancer, with an incidence of 24.5%. Rates of lymph node recurrence in range of lymph node dissection was low (13.9%). The median time of LRT was 20.0 (1.5-184.0) months. High range of recurrence was associated with significantly poorer OS in patients. Multiple linear regression analysis identified demonstrated N stage, tumor differentiation, adjuvant radiotherapy and total lymph nodes removed were association with recurrence range for patients. CONCLUSIONS: Supraclavicular and upper mediastinums lymph nodes were common recurrence site for ESCC patients , and careful initial staging and surveillance are needed. Thorough lymph node dissection may reduce the range of regional recurrence.

Bronchial epithelial transcriptomics and experimental validation reveal asthma severity-related neutrophilc signatures and potential treatments.

Airway epithelial transcriptome analysis of asthma patients with different severity was used to disentangle the immune infiltration mechanisms affecting asthma exacerbation, which may be advantageous to asthma treatment. Here we introduce various bioinformatics methods and develop two models: an OVA/CFA-induced neutrophil asthma mouse model and an LPS-induced human bronchial epithelial cell damage model. Our objective is to investigate the molecular mechanisms, potential targets, and therapeutic strategies associated with asthma severity. Multiple bioinformatics methods identify meaningful differences in the degree of neutrophil infiltration in asthma patients with different severity. Then, PTPRC, TLR2, MMP9, FCGR3B, TYROBP, CXCR1, S100A12, FPR1, CCR1 and CXCR2 are identified as the hub genes. Furthermore, the mRNA expression of 10 hub genes is determined in vivo and in vitro models. Reperixin is identified as a pivotal drug targeting CXCR1, CXCR2 and MMP9. We further test the potential efficiency of Reperixin in 16HBE cells, and conclude that Reperixin can attenuate LPS-induced cellular damage and inhibit the expression of them. In this study, we successfully identify and validate several neutrophilic signatures and targets associated with asthma severity. Notably, Reperixin displays the ability to target CXCR1, CXCR2, and MMP9, suggesting its potential therapeutic value for managing deteriorating asthma.

The application of three-dimensional custom-made prostheses in chest wall reconstruction after oncologic sternal resection.

BACKGROUND AND OBJECTIVES: As one of the cutting-edge advances in the field of reconstruction, three-dimensional (3D) printing technology has been constantly being attempted to assist in the reconstruction of complicated large chest wall defects. However, there is little literature assessing the treatment outcomes of 3D printed prostheses for chest wall reconstruction. This study aimed to analyze the surgical outcomes of 3D custom-made prostheses for the reconstruction of oncologic sternal defects and to share our experience in the surgical management of these rare and complex cases. METHODS: We summarized the clinical features of the sternal tumor in our center, described the surgical techniques of the application of 3D customized prosthesis for chest wall reconstruction, and analyzed the perioperative characteristics, complications, overall survival (OS), and recurrence-free survival of patients. RESULTS: Thirty-two patients with the sternal tumor who underwent chest wall resection were identified, among which 13 patients used 3D custom-made titanium implants and 13 patients used titanium mesh for sternal reconstruction. 22 cases were malignant, and chondrosarcoma is the most common type. The mean age was 46.9 years, and 53% (17/32) of the patients were male. The average size of tumor was 6.4 cm, and the mean defect area was 76.4 cm2. 97% (31/32) patients received R0 resection. Complications were observed in 29% (9/32) of patients, of which wound infection (22%, 7/32) was the most common. The OS of the patients was 72% at 5 years. CONCLUSION: We demonstrated that with careful preoperative assessment, 3D customized prostheses could be a viable alternative for complex sternal reconstruction.

Mitophagy plays a "double-edged sword" role in the radiosensitivity of cancer cells.

Mitochondria are organelles with double-membrane structure of inner and outer membrane, which provides main energy support for cell growth and metabolism. Reactive oxygen species (ROS) mainly comes from mitochondrial and can cause irreversible damage to cells under oxidative stress. Thus, mitochondrial homeostasis is the basis for maintaining the normal physiological function of cells and mitophagy plays a pivotal role in the maintenance of mitochondrial homeostasis. At present, to enhance the sensitivity of cancer cells to radiotherapy and chemotherapy by regulating mitochondria has increasingly become a hot spot of cancer therapy. It is particularly important to study the effect of ionizing radiation (IR) on mitochondria and the role of mitophagy in the radiosensitivity of cancer cells. Most of the existing reviews have focused on mitophagy-related molecules or pathways and the impact of mitophagy on diseases. In this review, we mainly focus on discussing the relationship between mitophagy and radiosensitivity of cancer cells around mitochondria and IR.

Analysis of Mechanical Characteristics of the Swing Angle Milling Head of a Heavy Computer Numerical Control Milling Machine and Research on the Light Weight of a Gimbal.

As the key component of a five-axis CNC planer-type milling machine, the integral mechanical property of the A/C swing angle milling head directly affects the machining accuracy and stability of the milling machine. Taking the mechanical A/C swing-angle milling head of a five-axis numerical-control gantry milling machine as the research object, the stress deformation characteristics and natural frequency of the swing-angle milling head under actual working conditions were studied using finite-element analysis. Based on the analytical results, it was determined that the cardan frame, with its large mass proportion and strong rigidity of the whole milling head, is the object to be optimized. The topological optimization of the cardan frame, in which achieving the minimum flexibility was the optimization objective, was carried out to determine the quality reduction area. By comparing the simulation results of the cardan frames of three different rib plate structures, it was shown that the cardan frame performance of the ten-type rib plate structure was optimal. The analytical results showed that, when the cardan frame met the design requirements for stiffness and strength, the mass after optimization was reduced by 13.67% compared with the mass before optimization, the first-order natural frequency was increased by 7.9%, and the maximum response amplitude was reduced in all directions to avoid resonance, which was beneficial to the improvement of the dynamic characteristics of the whole machine. At the same time, the rationality and effectiveness of the lightweight design method of the cardan frame were verified, which has strong engineering practicality. The research results provide an important theoretical basis for the optimization of other machine tool gimbals and have important practical significance and application value.

Controllable self-assembled DNA nanomachine enable homogeneous rapid electrochemical one-pot assay of lung cancer circulating tumor cells.

A homogeneous rapid (45 min) one-pot electrochemical (EC) aptasensor was established to quantitatively detect circulating tumor cells (CTCs) in lung cancer patients using mucin 1 as a marker. The core of this study is that the three single-stranded DNA (Y1, Y2, and Y3) could be hybridized to form Y-shaped DNA (Y-DNA) and further self-assemble to form DNA nanosphere. The aptamer of mucin 1 could be complementary and paired with Y1, thus disrupting the conformation of the DNA nanosphere. When mucin 1 was present, the aptamer combined specifically with mucin 1, thus preserving the DNA nanosphere structure. Methylene blue (MB) acted as a signal reporter, which could be embedded between two base pairs in the DNA nanosphere to form a DNA nanosphere-MB complex, reducing free MB and resulting in a lower electrochemical signal. The results demonstrated that the linear ranges for mucin 1 and A549 cells were 1 ag/mL-1 fg/mL and 1-100 cells/mL, respectively, with minimum detectable concentrations were 1 ag/mL and 1 cell/mL, respectively. The quantitative analysis of CTCs in 44 clinical blood samples was performed, and the results were consistent with the computerized tomography (CT) images, pathological findings and folate receptor-polymerase chain reaction (FR-PCR) kits. The receiver operating characteristic (ROC) curve exhibited an area under the curve (AUC) value of 0.970. The assay revealed 100% specificity and 94.1% sensitivity. It is believed that this electrochemical aptasensor could provide a new approach to detect CTCs.

YY1 modulates the radiosensitivity of esophageal squamous cell carcinoma through KIF3B-mediated Hippo signaling pathway.

Radiotherapy is an important strategy in the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). However, effectiveness of radiotherapy is still restricted by radioresistance. Herein, we aimed to understand the mechanisms underlying ESCC radioresistance, for which we looked into the potential role of YY1. YY1 was upregulated in radioresistant tissues and correlated with poor prognosis of patients with ESCC. YY1 depletion enhanced the radiosensitivity of ESCC in vitro and in vivo. Multi-group sequencing showed that downregulation of YY1 inhibited the transcriptional activity of Kinesin Family Member 3B (KIF3B), which further activated the Hippo signaling pathway by interacting with Integrin-beta1 (ITGB1). Once the Hippo pathway was activated, its main effector, Yes-associated protein 1 (YAP1), was phosphorylated in the cytoplasm and its expression reduced in the nucleus, thus enhancing the radiosensitivity by regulating its targeted genes. Our study provides new insights into the mechanisms underlying ESCC radioresistance and highlights the potential role of YY1 as a therapeutic target for ESCC.

Therapeutic Potential of Ginsenoside Rb1-PLGA Nanoparticles for Heart Failure Treatment via the ROS/PPARα/PGC1α Pathway.

(1) Background: Ginsenoside Rb1-PLGA nanoparticles (GRb1@PLGA@NPs) represent a novel nanotherapeutic system, yet their therapeutic efficacy and underlying mechanisms for treating heart failure (HF) remain unexplored. This study aims to investigate the potential mechanisms underlying the therapeutic effects of GRb1@PLGA@NPs in HF treatment; (2) Methods: The left anterior descending coronary artery ligation was employed to establish a HF model in Sprague-Dawley rats, along with an in vitro oxidative stress model using H9c2 myocardial cells. Following treatment with GRb1@PLGA@NPs, cardiac tissue pathological changes and cell proliferation were observed. Additionally, the serum levels of biomarkers such as NT-proBNP, TNF-α, and IL-1ß were measured, along with the expression of the ROS/PPARα/PGC1α pathway; (3) Results: GRb1@PLGA@NPs effectively ameliorated the pathological status of cardiac tissues in HF rats, mitigated oxidative stress-induced myocardial cell damage, elevated SOD and MMP levels, and reduced LDH, MDA, ROS, NT-proBNP, TNF-α, and IL-1ß levels. Furthermore, the expression of PPARα and PGC1α proteins was upregulated; (4) Conclusions: GRb1@PLGA@NPs may attenuate myocardial cell injury and treat HF through the ROS/PPARα/PGC1α pathway.

PPIs therapy has a negative impact on the clinical outcomes of advanced SCLC patients treated with PD-L1 inhibitors.

BACKGROUND: Programmed death-ligand 1 (PD-L1) inhibitors has emerged as a first-line therapeutic strategy for advanced small cell lung cancer (SCLC), which can stimulate T-cell activation, thereby preventing tumor avoidance of immunologic surveillance, whereas, proton pump inhibitors (PPIs) can play an important role in regulating immune function. This study assessed whether the concomitantly use of PPIs affected outcomes of immunotherapy in advanced SCLC. METHODS: Data from advanced SCLC patients who firstly treated with PD-L1 inhibitors between July 2018 and February 2021 was retrospectively analyzed. The impact of concomitant medications (especially PPIs) on objective response rate, progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Of 208 patients, 101 received immunotherapy concomitant PPIs. The median PFS of patients receiving PPIs (6.6 months) were significantly shorter than those without PPIs (10.6 months), and so was OS. There was associated with a 74.9% increased risk of progression and 58.3% increased risk of death. Both first-line and post-first-line immunotherapy, patients treated PPIs had poorer PFS. CONCLUSION: PPIs therapy has a negative impact on the clinical outcomes of advanced SCLC patients treated with PD-L1 inhibitors.

Preoperative cervical range of motion in flexion as a risk factor for postoperative cervical sagittal imbalance after laminoplasty.

STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate factors associated with cervical sagittal imbalance after cervical laminoplasty (LMP). SUMMARY OF BACKGROUND DATA: Preoperative dynamic cervical sagittal alignment is an important predictor for changes in cervical sagittal alignment and clinical outcomes after LMP. However, the impact of preoperative dynamic cervical sagittal alignment on postoperative changes in the cervical sagittal vertical axis (cSVA) after LMP remains unclear. We hypothesized that preoperative cervical flexion and extension function are associated with the changes in cSVA and clinical outcomes and found potential risk factors for post-LMP cervical sagittal imbalance (CSI). METHODS: Patients undergoing LMP at a single institution between January 2019 and December 2021 were retrospectively reviewed. The average follow-up period was 19 months. The parameters were collected before the surgery and at the final follow-up. We defined the changes in cSVA (△cSVA) ≤ -10 mm as the improvement group, -10 mm < △cSVA ≤ 10 mm as the stable group, and △cSVA > 10 mm as the deterioration group. Multivariate logistic regression was used to evaluate factors associated with postoperative CSI. The chi-square test was used to compare categorical data between groups. T-tests, ANOVA, Kruskal-Wallis tests, and Mann-Withney-Wilcoxon tests were used to assess the differences between radiographic and clinical parameters among groups. A receiver-operating characteristic curve (ROC) analysis was used to identify optimal cutoff values. RESULTS: The study comprised 102 patients with cervical spondylotic myelopathy. The Japanese Orthopedic Association (JOA) recovery rate was better in the improvement group and a significant aggravation in neck pain was observed in the deterioration group after surgery. Cervical Flex ROM (spine range of flexion) was significantly higher in the deterioration group. The multivariate logistic regression model suggested that greater Flex ROM and starting LMP at C3 were significant risk factors for postoperative deterioration of cervical sagittal balance. Receiver operating characteristic curves showed that the cut-off value for preoperative Flex ROM was 34.10°. CONCLUSION: Preoperative dynamic cervical sagittal alignment influences postoperative cervical sagittal balance after LMP. Cervical LMP should be carefully considered for patients with a preoperative high Flex ROM, as cervical sagittal imbalance is likely to occur after surgery. LEVEL OF EVIDENCE: 3.

Simplified Rapid Enrichment of CTCs and Selective Recognition Prereduction Enable a Homogeneous ICP-MS Liquid Biopsy Strategy of Lung Cancer.

The effective enrichment and hypersensitivity analysis of circulating tumor cells (CTCs) in clinical whole blood samples are highly significant for clinical tumor liquid biopsy. In this study, we established an easy operation and affordable CTCs extraction technique while simultaneously performing the homogeneous inductively coupled plasma mass spectrometry (ICP-MS) determination of CTCs in lung cancer clinical samples based on selective recognition reactions and prereduction phenomena. Our strategy allowed for the pretreatment of whole blood samples in less than 45 min after step-by-step centrifugation, which only required lymphocyte separation solution and erythrocyte lysate. Furthermore, a three-stage signal amplification system consisting of catalytic hairpin assembly (CHA), selective recognition for C-Ag+-C structures and Ag+ of copper sulfide nanoparticles (CuS NPs), and prereduction of Hg2+ through ascorbic acid (AA) was constructed by using mucin 1 as the CTCs marker and the aptamer for identification probes. In optimal conditions, the detection limits of ICP-MS were as low as 0.3 ag/mL for mucin 1 and 0.25 cells/mL for A549 cells. This method analyzed CTCs in 58 clinical samples quantitatively, and the results were consistent with clinical CT images and pathological findings. The area under the curve (AUC) value of the receiver operating characteristic (ROC) curve was 0.957, which provided a specificity of 100% and a sensitivity of 91.5% for the assay. Therefore, the simplicity of the extraction method, the accessibility, and the high sensitivity of the assay method make the strategies attractive for clinical CTCs testing applications.

Corrigendum: Host factor interaction networks identified by integrative bioinformatics analysis reveals therapeutic implications in COPD patients with COVID-19.

[This corrects the article DOI: 10.3389/fphar.2021.718874.].

The Chinese medicine Xin-tong-tai granule protects atherosclerosis by regulating oxidative stress through NOX/ROS/NF-κB signal pathway.

BACKGROUND: Xin-tong-tai Granule (XTTG), a traditional Chinese medicine, has been used to treat atherosclerosis (AS), but its mechanism is poorly understood. Intriguingly, oxidative stress has been recognized as vital factors in the treatment of atherosclerosis. PURPOSE: This study aims to explore the potential mechanism of XTTG for treating AS. METHODS: An in-vivo model of AS was established by feeding ApoE-/- mice with a high-fat diet (HFD), and the Human Aortic Vascular Smooth Muscle Cells (HAVSMCs) were induced by oxidized low-density lipoprotein (ox-LDL) in vitro. After treatment, the blood lipid levels and pathological aortic changes of each group were observed, and the cell proliferation and lipid droplet aggregation in each group were evaluated. The oxidative stress indicators such as malondialdehyde (MDA) and superoxide dismutase (SOD) levels and related NOX/ROS/NF-κB signaling pathway indicators were observed. RESULTS: XTTG improved blood lipid levels and pathological aortic changes of ApoE-/- mice with HFD feeding, inhibited HAVSMCs proliferation and lipid droplet aggregation induced by ox-LDL, reduced MDA content, increased SOD content, inhibited NOX4 and p22phox protein expression, downregulated ROS content, inhibited IKK-α, IKK-ß, NF-κB protein and mRNA expression and the phosphorylation of NF-κB. CONCLUSION: XTTG can inhibit NOX/ROS/NF-κB signaling pathway, reduce damages caused by oxidative stress, and exert anti-AS effects.

Analysis of heart displacement during thoracic radiotherapy based on electrocardiograph-gated 4-dimensional magnetic resonance imaging.

Background: Periodic cardiac movement may expose the heart to radiation field induced damage, leading to radiation-induced heart disease (RIHD). Studies have proven that delineation of the heart based on planning CT fails to show the real margin of the substructures and a compensatory margin should be applied. The purpose of this study was to quantify the dynamic changes and the compensatory extension range by breath-hold and electrocardiogram gated 4-dimensional magnetic resonance imaging (4D-MRI), which had the advantage of discriminating soft tissues. Methods: Eventually, 15 patients with oesophageal or lung cancers were enrolled, including one female and nine males aged from 59 to 77 years from December 10th, 2018, to March 4th, 2020. The displacement of the heart and its substructures was measured through a fusion volume and the compensatory expansion range was calculated by expending the boundary on the planning CT to that of the fusion volume. The differences were tested through the Kruskal-Wallis H test and were considered significant at a two-side P<0.05. Results: The extent of movement of heart and its substructures during one cardiac cycle were approximately 4.0-26.1 millimetre (mm) in anterior-posterior (AP), left-right (LR), and cranial-caudal (CC) axes, and the compensatory margins should be applied to planning CT by extending the margins by 1.7, 3.6, 1.8, 3.0, 2.1, and 2.9 centimetres (cm) for pericardium; 1.2, 2.5, 1.0, 2.8, 1.8, and 3.3 cm for heart; 3.8, 3.4, 3.1, 2.8, 0.9, and 2.0 cm for interatrial septum; 3.3, 4.9, 2.0, 4.1, 1.1, and 2.9 cm for interventricular septum; 2.2, 3.0, 1.1, 5.3, 1.8, and 2.4 cm for left ventricular muscle (LVM); 5.9, 3.4, 2.1, 6.1, 5.4, and 3.6 cm for antero-lateral papillary muscle (ALPM); and 6.6, 2.9, 2.6, 6.6, 3.9, and 4.8 cm for postero-medial papillary muscle (PMPM) in anterior, posterior, left, right, cranial, and caudal directions, respectively. Conclusions: Periodic cardiac activity causes obvious displacement of the heart and its substructures, and the motion amplitude of substructures differs. Extending a certain margin as the compensatory extension to represent the organs at risk (OAR) and then limiting the dose-volume parameters could be performed in clinical practice.

Sintilimab as maintenance treatment for local/regional recurrent esophageal squamous carcinoma after concurrent chemoradiotherapy: a single-arm Ib/II phase study.

Background: Esophageal cancer (EC) is an aggressive neoplasm of the gastrointestinal tract that is usually treated with a combination of chemotherapy, radiotherapy (RT), and/or surgery, according to disease status. Despite the availability of multimodal therapeutic strategies, local recurrence is frequently observed. However, there is no standard treatment or promising therapeutic approach for local recurrence or metastatic esophageal carcinoma after the RT. This study tended to investigate the efficacy and safety of sintilimab maintenance after concurrent chemoradiotherapy (CCRT) for local/regional recurrent esophageal squamous carcinoma. Methods: This study was a single-arm, phase Ib/II trial conducted in a single site in China. Patients previously radically treated (surgery or CCRT), histologically confirmed, local or regional recurrence esophageal squamous carcinoma, qualified for the study design, were treated with 25-28 times radiotherapy plus raltitrexed once every 3 weeks for up to two cycles. Patients who have not progressed after CCRT received sintilimab as maintenance once every 3 weeks up to 1 year. Primary endpoints were overall survival (OS) and safety. Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). Results: Between September 2019 and March 2022, in a total of 36 enrolled patients, 34 pts completed CCRT. Three patients excluded due to violation of the exclusion criteria (1 pt) and consent withdrawal (2 pts). Finally, 33 pts were included in the final analysis, in which 3 pts had disease progression, and the remaining 30 entered maintenance therapy with sintilimab. The median follow-up time was 12.3 months. Median OS was 20.6 months (95%CI 10.5-NA) and the 1-year OS rate was 64%. Median PFS was 11.5 months (95%CI 5.29-21.3) and the 1-year PFS rate was 43.6%. The ORR was 63.6% (95%CI 44.6-77.8), including 2 cases of CR and 19 cases of PR. The DCR was 19.9%, the median DOR was 19.5 months, and the median TTR was 2.4 months. The rate of any grade TRAEs was 96.7%; ≥Grade 3 TRAE was 23.4%. The incidence of immune-related AE was 60%, most of which were grade 1-2, and only one case of thyroid-stimulating hormone increased was irAE with grade 3 or above. Conclusion: Sintilimab has shown promising clinical efficacy and a manageable safety profile as maintenance therapy after CCRT for local/regional recurrent esophageal squamous carcinoma. In addition, further confirmation from a large-scale real-world study is still needed.

SnCo Nanoparticles Loaded in Hollow Carbon Spheres Interlinked by N-Doped Carbon Fibers for High-Performance Sodium-Ion Batteries.

The development of Sn-based materials with electrochemically inactive matrices is a novel strategy to alleviate the volume expansion and giant structure strain/stress during the sodiation/desodiation process. In this work, a freestanding membrane based on the unique bean pod-like host composed by nitrogen-doped carbon fibers and hollow carbon spheres (HCSs) encapsulated with SnCo nanoparticles is synthesized by electrospinning (B-SnCo/NCFs). In this unique bean pod-like structure, Sn acts as a host for Na+ storage, while the Co plays the important role of an electrochemically inactive matrix that can not only buffer the volume variations but also inhibit aggregation and particle growth of the Sn phase during the electrochemical Na-Sn alloying process. Meanwhile, the introduction of hollow carbon spheres can not only provide enough sufficient void space to withstand the volume expansion during the (de)sodiation processes but also improve the conductivity of the anode along the carbon fibers. Furthermore, the B-SnCo/NCF freestanding membrane can increase the contact area between the active material and the electrolyte, which can provide more active sites during the cycling process. When used as an anode material for Na-ion batteries, the freestanding B-SnCo/NCF anode exhibits an outstanding rate capacity of 243.5 mA h g-1 at 1.6 A g-1and an excellent specific capacity of 351 mA h g-1 at 0.1 A g-1 for 300 cycles.

Factors related to T1 slope: spinopelvic balance and thoracic compensation.

OBJECTIVE: To identify factors associated with T1 slope (T1S). METHODS: A total of 215 patients over 18 years old who underwent whole-spine X-rays to evaluate lower back pain were enrolled in this study. T1S, pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), cervical lordosis (CL), thoracolumbar kyphosis (TLK), and sagittal vertical axis (SVA) were measured. Patients were divided into balance, compensatory balance, thoracic compensation, and thoracic decompensation groups. RESULTS: TK (p < 0.001), SVA (p < 0.001), and CL (p = 0.020) were significantly related to high T1S. The balance group had the smallest PT, largest SS and largest LL of the four groups (p < 0.001). The thoracic compensation group had the smallest TK of all groups (p < 0.001). There was no significant difference in T1S between the balance and thoracic compensation groups (p = 0.099). The thoracic decompensation group had a larger T1S than the balance group (p = 0.023). CONCLUSIONS: Caudal spine segments had a sequential effect on cranial spine segments. T1S reflected the compensation ability of the spine. The absence of balance tended to increase the T1S. Pelvic posterior rotation and thoracic compensation were two crucial factors protecting against increased T1S in patients with ASD.

A new risk score model based on lactate dehydrogenase for predicting prognosis in esophageal squamous cell carcinoma treated with chemoradiotherapy.

Background: The prognostic role of lactate dehydrogenase (LDH) has been confirmed in many malignant tumors, but it has not been widely discussed in esophageal squamous cell cancer (ESCC). This study aimed to assess the prognostic value of LDH in patients with ESCC and to generate a risk score model to predict prognosis in patients who were treated with chemoradiotherapy. Methods: A total of 614 patients with ESCC who received chemoradiotherapy from 2012 to 2016 were examined in this single-center retrospective study. The optimal cutoff points for age, cytokeratin 19 fragment antigen 21-1 (Cyfra21-1), carcinoembryonic antigen (CEA), tumor length, total dose, and LDH were calculated by the X-tile software. We analyzed the association between the level of LDH and clinicopathological characteristics, and a 1:3 propensity score matching analysis was used to compensate for differences in baseline characteristics. Kaplan-Meier and Cox regression models were used to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). Based on the results, we developed a corresponding risk score model and established a nomogram to assess its predictive capacity. Results: The optimal cutoff point of LDH was 134 U/L. Patients in the high-LDH group had significantly shorter PFS and worse OS than did those in the low-LDH group (all P values <0.05). Multivariate survival analysis indicated that pretreatment serum LDH level (P=0.039), Cyfra21-1 level (P=0.003), tumor length (P=0.013), clinical N stage (P=0.047), and clinical M stage (P=0.011) were independent predictors for OS in patients with ESCC who underwent chemoradiotherapy. Furthermore, a risk score model based on these 5 prognostic factors was established to divide patients into 3 prognostic groups to identify those patients with ESCC who were most likely to benefit from chemoradiotherapy (χ2=20.53; P<0.0001). However, the prediction nomogram that integrated the significant independent factors for OS is not performed very well in predicting survival (C-index =0.599). Conclusions: Pretreatment serum LDH level may be a reliable factor in predicting the therapeutic effect of chemoradiotherapy in ESCC. Further validation is needed before this model can be widely used in clinical practice.