The preservation of cervical flexibility helps maintain cervical sagittal alignment after laminoplasty.

BACKGROUND CONTEXT: Cervical spine range of motion (ROM) is a critical factor in changes in cervical sagittal alignment (CSA) and clinical outcomes after cervical laminoplasty (LMP). However, the impact of postoperative cervical ROM on CSA after cervical LMP is still unclear. PURPOSE: Evaluating the imaging and symptomatic data from patients with cervical spondylotic myelopathy (CSM) to identify the influence of postoperative cervical ROM on post-LMP CSA and surgical outcomes. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: Eighty-six patients undergoing LMP due to multilevel CSM OUTCOME MEASURES: Radiographic parameters were measured before surgery and at follow-up: cervical lordosis (CL), T1 slope (T1S), cervical sagittal vertical axis (cSVA), CL in flexion (Flex CL), CL in extension (Ext CL), total cervical spine range of motion (ROM), cervical spine range of flexion (Flex ROM), and cervical spine range of extension (Ext ROM). Japanese Orthopedic Association (JOA) and visual analog score (VAS) were used to assessed clinical outcomes. Other parameters included age, gender, body mass index (BMI), follow-up time, number of surgical segments, proximal level, distalis level, and collar wear time. METHODS: We divided patients according to the changes in CSA (loss of cervical lordosis (LCL)>10°, or ≤10°; an increase in cervical sagittal vertical axis (I-cSVA) >10mm, or ≤10mm). A receiver-operating characteristic curve (ROC) analysis was constructed to identify the optimal cut-off value to discriminate the patients with and without postoperative deterioration of CSA. RESULTS: The postoperative total and Flex ROM were significantly lower in the LCL>10° and I-cSVA>10mm groups. Multivariate logistic regression analysis showed that low post-Flex ROM was significant risk factor for postoperative deterioration of CSA. ROC showed that the cut-off value for postoperative Flex ROM was 15.60°. Improvements in JOA recovery rate and neck pain were more significant in the flexibility group (post-Flex ROM ≥15.6°) after surgery. Patients in the stiffness group (post-Flex ROM <15.6°) wore a collar longer. CONCLUSIONS: The preservation of cervical flexibility can maintain CSA after cervical LMP. Postoperative cervical stiffness is related to poor surgical outcomes because significant cervical kyphotic change and sagittal imbalance are likely to occur after surgery. Prolonged wearing of cervical collar is correlated with cervical stiffness following cervical LMP.

Accelerated and Guided Zn2+ Diffusion via Polarized Interface Engineering Toward High Performance Wearable Zinc-Ion Batteries.

Rechargeable aqueous Zn-ion batteries (ZIBs) are considered as a new energy storage device for wearable electronic equipment. Nowadays, dendrite growth and uneven deposition of zinc have been the principal problems to suppress the development of high-performance wearable zinc-ion batteries. Herein, a perovskite material of LaAlO3 nanoparticle has been applied for interface engineering and zinc anode protection. By adjusting transport channels and accelerating the Zn2+ diffusion, the hydrogen evolution reaction potential is improved, and electric field distribution on the Zn electrode surface is regulated to navigate the fast and uniform deposition of Zn2+. As a proof of demonstration, the assembled LAO@Zn||MnO2 batteries can display the highest capacity of up to 140 mAh g-1 without noticeable decay even after 1000 cycles. Moreover, a motor-driven fan and electronic wristwatch powered by wearable ZIBs can demonstrate the practical feasibility of LAO@Zn||MnO2 in wearable electronic equipment.

Prospects for the Protective Mechanisms and Compounds of Bufei Huoxue Capsule against COVID-19 Convalescence: Evaluation of Integrating UHPLC-HRMS Analysis and Network Pharmacology Strategy.

INTRODUCTION: Most COVID-19 survivors are troubled with chronic persistent symptoms, which have currently no definitive treatments. Bufei Huoxue (BFHX) capsule exerts clinical benefit, while the material basis and molecular mechanism remain unclear. AIM: The study aimed to elucidate the protective mechanisms of BFHX capsules against COVID-19 convalescence. UHPLC-HRMS and various databases were employed to explore potential compounds and targets. PPI, MCODE, transcription factor (TF), and miRNA analyses were conducted to receive hub targets and corresponding upstream regulators. METHOD: Molecular docking was applied to verify the binding activity of compound and target. Further, GO, KEGG, WIKI, and Reactome analyses were performed, and compound-targetsymptom and gene-disease networks were constructed. A total of 127 compounds and 313 targets were acquired. A sum of 10 hub targets were screened and showed good binding affinities with critical compounds. RESULT: MLLT1, CBFB, and EZH2 were identified as key TFs, and hsa-mir-146a-5p, hsa-mir- 26b-5p, and hsa-mir-24-3p were predicted to be important miRNAs. BFHX capsule may alleviate the symptoms by targeting TNF, IL-6, IFNG, and TGF-ß1. Besides, BFHX capsule may exert a therapeutic effect on respiratory disease (especially pulmonary fibrosis and lung infection) and multi-system damage during COVID-19 convalescence by regulating cytokine-cytokine receptor interaction, as well as TGF-ß, TNF, and Toll-like receptor signaling pathways. CONCLUSION: In summary, BFHX capsule may exert a therapeutic effect on multi-system damages during COVID-19 convalescence through multiple compounds (such as albiflorin, isopsoralen, and neobavaisoflavone), multiple targets (such as TNF, IL-6, and EGF) and multiple pathways (TGF-ß, TNF, and Toll-like receptor signaling pathways).

Efficacy and relative safety of caplacizumab in immune-mediated thrombotic thrombocytopenic purpura: a systematic review and meta-analysis.

Immune-mediated thrombotic thrombocytopenia purpura (iTTP) is a rare microvascular disease characterized by severe disseminated microvascular thrombose-bleeding syndrome. Caplacizumab has been approved for the treatment of iTTP in combination with Plasma Exchange (PE) and immunosuppressive therapy, but its role in iTTP therapy remains uncertain. Therefore, we conducted a meta-analysis to investigate the safety and efficacy of caplacizumab for the treatment of patients with iTTP. We searched electronic databases (PubMed, Embase, Cochrane Library, and Scopus) and reference lists of relevant articles to find articles published from 2015 to 2022. The time to normalization of the platelet count of the group caplacizumab is shorter than the group placebo (SMD = -0.72; 95% CI -0.88 to -0.56; P  < 0.05). Caplacizumab reduced the incidence of mortality (OR = 0.41; 95% CI 0.18-0.92; P  < 0.05), exacerbations (OR = 0.10; 95% CI 0.05-0.18; P  < 0.05), and recurrence (OR = 0.17; 95% CI 0.06-0.50; P  < 0.05). However, the bleeding events in the caplacizumab group were higher than those in the placebo group, especially severe bleeding events. There was no difference in ADAMTS13 activity and thromboembolic events between the two groups. Our analysis indicated that caplacizumab is effective and well tolerated for the treatment of iTTP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022362370.

Change of cervical flexion range of motion influences postoperative sagittal alignment of the cervical spine after laminoplasty.

OBJECTIVE: The relationships between preoperative cervical spine range of motion (ROM) and postoperative cervical sagittal alignment (CSA), and clinical outcomes after laminoplasty (LMP) have been widely studied. However, the impact of ROM changes on postoperative CSA and clinical outcomes after LMP remains unclear. Herein, patients with cervical spondylotic myelopathy (CSM) were retrospectively analyzed to explore the association between postoperative cervical ROM changes and CSA and surgical outcomes. METHODS: Patients who underwent cervical LMP at our hospital between January 2019 to June 2022 were retrospectively reviewed. CSA parameters were measured before the surgery and at the final follow-up. Loss of cervical lordosis (LCL) was defined as preoperative cervical lordosis (CL) - postoperative CL. An increase in the cervical sagittal vertical axis (I-cSVA) was defined as postoperative cervical sagittal vertical axis (cSVA) - preoperative cSVA. We defined the changes in cervical flexion range of motion (△Flex ROM, preoperative Flex ROM minus postoperative Flex ROM) > 10° as L- Flex ROM group, and △Flex ROM ≤ 10° as S- Flex ROM group. Japanese Orthopedic Association (JOA) score and visual analog score (VAS) were used to assess the surgical outcomes. RESULTS: The study comprised 74 patients and the average follow-up period was 31.83 months. CL, total ROM, and Flex ROM decreased and cSVA increased after cervical LMP. LCL and I-cSVA were positively correlated with △Flex. Multiple linear regression analysis showed that a decrease in the Flex ROM was a risk factor for LCL and I-cSVA after LMP. LCL and I-cSVA were higher in the L-Flex ROM group than in the S-Flex ROM group. Postoperative JOA and the JOA recovery rate were worse in the L-Flex ROM group than in the S-Flex ROM group. CONCLUSIONS: Cervical total and Flex ROM decreased after cervical LMP. The reduction of Flex ROM was associated with LCL and I-cSVA after surgery. The preservation of cervical Flex ROM helps maintain CSA after LMP. Therefore, more attention should be paid to maintaining cervical ROM to obtain good CSA and surgical effects after cervical LMP.

Network and Experimental Pharmacology on Mechanism of Yixintai Regulates the TMAO/PKC/NF-κB Signaling Pathway in Treating Heart Failure.

Objective: This study aims to explore the mechanism of action of Yixintai in treating chronic ischemic heart failure by combining bioinformatics and experimental validation. Materials and Methods: Five potential drugs for treating heart failure were obtained from Yixintai (YXT) through early mass spectrometry detection. The targets of YXT for treating heart failure were obtained by a search of online databases. Gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted on the common targets using the DAVID database. A rat heart failure model was established by ligating the anterior descending branch of the left coronary artery. A small animal color Doppler ultrasound imaging system detected cardiac function indicators. Hematoxylin-eosin (HE), Masson's, and electron microscopy were used to observe the pathological morphology of the myocardium in rats with heart failure. The network pharmacology analysis results were validated by ELISA, qPCR, and Western blotting. Results: A total of 107 effective targets were obtained by combining compound targets and eliminating duplicate values. PPI analysis showed that inflammation-related proteins (TNF and IL1B) were key targets for treating heart failure, and KEGG enrichment suggested that NF-κB signaling pathway was a key pathway for YXT treatment of heart failure. Animal model validation results indicated the following: YXT can significantly reduce the content of intestinal microbiota metabolites such as trimethylamine oxide (TMAO) and improve heart failure by improving the EF and FS values of heart ultrasound in rats and reducing the levels of serum NT-proBNP, ANP, and BNP to improve heart failure. Together, YXT can inhibit cardiac muscle hypertrophy and fibrosis in rats and improve myocardial ultrastructure and serum IL-1ß, IL-6, and TNF-α levels. These effects are achieved by inhibiting the expressions of NF-κB and PKC. Conclusion: YXT regulates the TMAO/PKC/NF-κB signaling pathway in heart failure.

Fluorine-ion-regulated yolk-shell carbon-silicon anode material for high performance lithium ion batteries.

Silicon is considered as the next-generation anode material for lithium-ion batteries due to its high theoretical specific capacity and abundant crustal abundance. However, its poor electrical conductivity results in slow diffusion of lithium ions during battery operation. Simultaneously, the alloying process of silicon undergoes a 300 % volume change, leading to structural fractures in silicon during the cycling process. As a result, it loses contact with the current collector, continuously exposing active sites, and forming a sustained solid electrolyte interface (SEI) membrane. This paper presents the design of a fluorine-ion-regulated yolk-shell carbon-silicon anode material, highlighting the following advantages: (a) Alleviating volume changes through the design of a yolk-shell structure, thereby maintaining material structural integrity during cycling. (b) Carbon shell prevents silicon from coming into contact with the electrolyte, simultaneously improving silicon's electrical conductivity and increasing ion/electron conductivity. (c) Utilizing fluorine-ion interface modification to obtain an SEI membrane rich in fluorine components (such as LiF), thereby enhancing its long cycling performance. The F-Si@Void@C exhibits outstanding electrochemical performance, with a reversible capacity of 1166 mAh/g after 900 cycles at a current density of 0.5 A/g.

How does cervical sagittal profile change after the spontaneous compensation of global sagittal imbalance following one- or two-level lumbar fusion.

PURPOSE: This study aimed to evaluate the cervical sagittal profile after the spontaneous compensation of global sagittal imbalance and analyze the associations between the changes in cervical sagittal alignment and spinopelvic parameters. METHODS: In this retrospective radiographic study, we analyzed 90 patients with degenerative lumbar stenosis (DLS) and sagittal imbalance who underwent short lumbar fusion (imbalance group). We used 60 patients with DLS and sagittal balance as the control group (balance group). Patients in the imbalance group were also divided into two groups according to the preoperative PI: low PI group (≤ 50°), high PI group (PI > 50°). We measured the spinal sagittal alignment parameters on the long-cassette standing lateral radiographs of the whole spine. We compared the changes of spinal sagittal parameters between pre-operation and post-operation. We observed the relationships between the changes in cervical profile and spinopelvic parameters. RESULTS: Sagittal vertical axis (SVA) occurred spontaneous compensation (p = 0.000) and significant changes were observed in cervical lordosis (CL) (p = 0.000) and cervical sagittal vertical axis (cSVA) (p = 0.023) after surgery in the imbalance group. However, there were no significant differences in the radiographic parameters from pre-operation to post-operation in the balance group. The variations in CL were correlated with the variations in SVA (R = 0.307, p = 0.041). The variations in cSVA were correlated with the variations in SVA (R=-0.470, p = 0.001). CONCLUSION: Cervical sagittal profile would have compensatory changes after short lumbar fusion. The spontaneous decrease in CL would occur in patients with DLS after the spontaneous compensation of global sagittal imbalance following one- or two-level lumbar fusion. The changes of cervical sagittal profile were related to the extent of the spontaneous compensation of SVA.

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. The authors 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 and overall survival. 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 LNR 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 LNR 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.

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.

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.

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 (CSI) 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 CSI. PATIENTS AND 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 χ 2 test was used to compare categorical data between groups. T tests, analysis of variance, Kruskal-Wallis tests, and Mann-Whitney Wilcoxon tests were used to assess the differences between radiographic and clinical parameters among groups. A receiver operating characteristic curve analysis was used to identify optimal cutoff values. RESULTS: The study comprised 102 patients with cervical spondylotic myelopathy. The Japanese Orthopedic Association 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 range of motion (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 cutoff 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 CSI is likely to occur after surgery. LEVEL OF EVIDENCE: Level 3.

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.

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.