Swallowing rehabilitation of patients undergoing T-tube implantation for the treatment of laryngotracheal stenosis.

OBJECTIVE: Patients with laryngotracheal stenosis (LTS) often have dysphagia after laryngotracheal reconstruction with T-tube insertion, which affects the quality of life. The purpose of this study is to observe the effect of swallowing rehabilitation therapy on the improvement of quality of life in patients of otolaryngology-head and neck surgery with dysphagia undergoing T-tube implantation treatment through longitudinal study. METHODS: Thirty-eight patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation were recruited. All patients received swallowing rehabilitation therapy. The assessment of swallowing function was performed using the 10-item Eating Assessment Tool (EAT-10), the 30 mL water swallow test (WST), and flexible endoscopic evaluation of swallow (FEES). RESULTS: After swallowing rehabilitation therapy, timing of swallowing, grade of dysphagia, performance on FEES and 30 mL WST, and EAT-10 score all improved. Thirty-eight patients successfully transitioned to oral feeding and were able to remove their nasogastric tubes without experiencing any complications, including aspiration pneumonia. CONCLUSION: For patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation, swallowing rehabilitation therapy could improve swallowing function of the patients, so as to reduce the potential harm caused by the pain and complications of surgery experienced by patients.

Development and Validation of a Clinic Machine Learning Classifier for the Prediction of Risk Stratifications of Prostate Cancer Bone Metastasis Progression to Castration Resistance.

Objective: To explore the predictive factors and predictive model construction for the progression of prostate cancer bone metastasis to castration resistance. Methods: Clinical data of 286 patients diagnosed with prostate cancer with bone metastasis, initially treated with endocrine therapy, and progressing to metastatic castration resistant prostate cancer (mCRPC) were collected. By comparing the differences in various factors between different groups with fast and slow occurrence of castration-resistant prostate cancer (CRPC). Kaplan-Meier survival analysis and COX multivariate risk proportional regression model were used to compare the differences in the time to progression to CRPC in different groups. The COX multivariate risk proportional regression model was used to evaluate the impact of candidate factors on the time to progression to CRPC and establish a predictive model. The accuracy of the model was then tested using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results: The median time for 286 mCRPC patients to progress to CRPC was 17 (9.5-28.0) months. Multivariate analysis showed that the lowest value of PSA (PSA nadir), the time when PSA dropped to its lowest value (timePSA), and the number of BM, and LDH were independent risk factors for rapid progression to CRPC. Based on the four independent risk factors mentioned above, a prediction model was established, with the optimal prediction model being a random forest with area under curve (AUC) of 0.946[95% CI: 0.901-0.991] and 0.927[95% CI: 0.864-0.990] in the training and validation cohort, respectively. Conclusion: After endocrine therapy, the PSA nadir, timePSA, the number of BM, and LDH are the main risk factors for rapid progression to mCRPC in patients with prostate cancer bone metastases. Establishing a CRPC prediction model is helpful for early clinical intervention decision-making.

The impact of frailty on clinical outcomes of older patients undergoing enhanced recovery after lumbar fusion surgery: A prospective cohort study.

BACKGROUND: Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. ERAS can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains. MATERIALS AND METHODS: An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged ≥75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP ≥ 3). The preoperative variables, operative data, postoperative outcomes and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay (LOS) after surgery. RESULTS: A total of 245 patients (age of 79.8 ± 3.4 yr) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between non-frail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery. CONCLUSION: Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults.

S100 protein family: Emerging role and mechanism in digestive tract cancer (Review).

Digestive tract cancer is one of the most common types of cancers globally, with ~4.8 million new cases and 3.4 million cancer­associated deaths in 2018, accounting for 26% of cancer incidence and 35% of cancer­related deaths worldwide. S100 protein family is involved in regulating cancer cell proliferation, angiogenesis, epithelial­mesenchymal transition (EMT), metastasis, metabolism and immune microenvironment homeostasis. The critical role of S100 protein family in digestive tract cancer involves complicated mechanisms, such as cancer stemness remodeling, anaerobic glycolysis regulation, tumor­associated macrophage differentiation and EMT. The present study systematically reviewed published studies on the compositions, function and the underlying molecular mechanisms of the S100 family, as well as guidance for diagnosis, treatment and prognosis of digestive tract cancer. Systematic review of the roles and underlying molecular mechanisms of S100 protein family may provide new insight into exploring potential cancer biomarkers and the optimized therapeutic strategies for digestive tract cancer.

Mesenchymal stem cells derived from CHIR99021 and TGF­ß induction remained on the colicomentum and improved cardiac function of a rat model of acute myocardium infarction.

Human induced pluripotent stem cells (hiPSCs) have been regarded as a potential stem cell source for cell therapy. However, the production of cells with mesenchymal potential from hiPSCs through spontaneous differentiation is time consuming and laborious. In the present study, the combined use of the GSK-3 inhibitor CHIR99021 and TGF-ß was used to obtain mesenchymal stem cell (MSC)-like cells from hiPSCs. During the induction process, the transcription of epithelial-mesenchymal transition (EMT)-related genes N-cadherin and Vimentin in the transformed cells was upregulated, whereas the transcription of E-cadherin and pluripotency-related transcription factors SOX2, OCT4 and NANOG did not change significantly. This indicated that whilst cells were pluripotent, EMT was initiated by the upregulation of transcription of EMT promoting genes. Both SMAD-dependent and independent signalling pathways were significantly activated by the combined induction treatment compared with the single factor induction. The hiPSC-derived MSC-like cells (hiPSC-MSCs) expressed MSC-related markers and acquired osteogenic, chondrogenic and adipogenic differentiation potentials. After being injected into the peritoneal cavity of rats, the hiPSC-MSCs secreted angiogenic and immune-regulatory factors and remained on the colicomentum for 3 weeks. Within an 11-week period, four intraperitoneal hiPSC-MSC injections (1x107 cells/injection) into acute myocardial infarction (AMI) model rats significantly increased the left ventricular ejection fraction, left ventricular fractional shortening and angiogenesis and significantly reduced scar size and the extent of apoptosis in the infarcted area compared with that of the control PBS injection. Symptoms of hiPSC-MSC-induced immune reaction or tumour formation were not observed over the course of the experiment in the hiSPC-MSC treated rats. In conclusion, the CHIR99021 and TGF-ß combined induction was a rapid and effective method to obtain MSC-like cells from hiPSCs and multiple high dose intraperitoneal injections of hiPSC-derived MSCs were safe and effective at restoring cardiac function in an AMI rat model.

Predictors of achieving minimal clinically important difference in functional status for elderly patients with degenerative lumbar spinal stenosis undergoing lumbar decompression and fusion surgery.

OBJECTIVE: To identify the predictors for the achievement of minimal clinically important difference (MCID) in functional status among elderly patients with degenerative lumbar spinal stenosis (DLSS) undergoing lumbar decompression and fusion surgery. METHODS: Patients who underwent lumbar surgery for DLSS and had a minimum of 1-year follow-up were included. The MCID achievement threshold for the Oswestry Disability Index (ODI) was set at 12.8. General patient information and the morphology of lumbar paraspinal muscles were evaluated using comparative analysis to identify influencing factors. Multiple regression models were employed to identify predictors associated with MCID achievement. A receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off values for predicting functional recovery. RESULTS: A total of 126 patients (46 males, 80 females; mean age 73.0 ± 5.9 years) were included. The overall rate of MCID achievement was 74.6%. Patients who achieved MCID had significantly higher psoas major muscle attenuation (43.55 vs. 39.23, p < 0.001) and preoperative ODI (51.5 vs. 41.6, p < 0.001). Logistic regression showed that elevated psoas major muscle attenuation (p = 0.001) and high preoperative ODI scores (p = 0.001) were independent MCID predictors. The optimal cut-off values for predicting MCID achievement were found to be 40.46 Hounsfield Units for psoas major muscle attenuation and 48.14% for preoperative ODI. CONCLUSION: Preoperative psoas major muscle attenuation and preoperative ODI were reliable predictors of achieving MCID in geriatric patients undergoing lumbar decompression and fusion surgery. These findings offer valuable insights for predicting surgical outcomes and guiding clinical decision-making in elderly patients.

Evidence of MRI image features and inflammatory biomarkers association with low back pain in patients with lumbar disc herniation.

BACKGROUND CONTEXT: While MRI image features and inflammatory biomarkers are frequently used for guiding treatment decisions in patients with lumbar disc herniation (LDH) and low back pain (LBP), our understanding of the connections between these features and LBP remains incomplete. There is a growing interest in the potential significance of MRI image features and inflammatory biomarkers, both for quantification and as emerging therapeutic tools for LBP. PURPOSE: To investigate the evidence supporting MRI image features and inflammatory biomarkers as predictors of LBP and to determine their relationship with pain intensity. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: All consecutive patients with LDH who underwent discectomy surgery at our institution from February 2020 to June 2023 at the author's institution were included. OUTCOME MEASURES: MRI image features in discogenic, osseous, facetogenic, and paraspinal muscles, as well as inflammatory biomarkers in serum (including CRP (C-reactive protein), ESR (erythrocyte sedimentation rate), PCT (procalcitonin), TNF (tumor necrosis factor), interleukin-1 beta (IL-1ß), and IL-6), and paraspinal muscles (including TNF, IL-1ß, IL-6, IL-10, and transforming growth factor beta 1 (TGF-ß1)). METHODS: A series of continuous patients diagnosed with LDH were categorized into acute LBP (<12 weeks), chronic LBP (≥12 weeks), and nonLBP groups. MRI image features and inflammatory biomarkers relation to pain intensity was assessed using the independent t-test, Chi-squared tests, Spearman rank correlation coefficient, and logistic regression test. RESULTS: Compared to the nonLBP group, the chronic LBP group exhibited a higher incidence of intervertebral disc (IVD) degeneration (≥ grade 3) and high-fat infiltration in paraspinal muscles, alongside a significant reduction in the cross-sectional area (CSA) and fatty degeneration of the multifidus muscle. Furthermore, there was a greater expression of IL-6 in serum and TNF in paraspinal muscles in the chronic LBP group and a greater expression of CRP and IL-6 in serum and TNF in paraspinal muscles in the acute LBP group. CSA and fatty degeneration of multifidus muscle were moderately negatively correlated with chronic LBP scores. The expression of TNF and IL-6 in serum and the expression of TNF in the multifidus muscle were moderately correlated with preoperative LBP. IVD degeneration and high-fat infiltration were identified as risk factors for chronic LBP. CONCLUSION: The results provide evidence that IVD degeneration, high-fat infiltration, and the reduction of CSA in paraspinal muscles were associated with the development of chronic LBP in patients with LDH, and these associations are linked to inflammatory regulation. This deepens our understanding of the etiology and pathophysiology of LBP, potentially leading to improved patient stratification and more targeted interventions.

Links among MRI features in paraspinal muscles, inflammatory processes, and related back pain in patients with lumbar disc herniation.

Background: Recent studies have provided evidence that structural changes in paraspinal muscles are associated with intervertebral disc degeneration (IDD), ubiquitous with low back pain (LBP), and potentially thought to be regulated by inflammatory processes. However, the links remain unclear. Objective: The aims of this study were to investigate structural changes in paraspinal muscles that differed in healthy and lumbar disc herniation (LDH) patients, and LDH patients with and without LBP, and to determine the link with the expression of inflammatory marker(s). Methods: Cross-sectional areas (CSAs) and fatty degeneration of muscles were measured in this prospective cohort study. Multifidus muscle (MM) tissue was procured from included individuals undergoing surgery. Gene expression was quantified using qPCR assays. Independent t-test, Chi-square, and Spearman correlation were used for evaluating the links among structural changes, expression of inflammatory markers, and clinical outcomes. Results: Functional CSA and fatty degeneration of MM were larger in healthy group than LDH group. A significant increase in fat infiltration in MM in LBP group than in non-LBP group. TNF-alpha (TNF-α) was 28-fold greater in high-fat infiltration group than low-fat infiltration group within MM. Expression of TNF-α and IL-1ß in MM was moderately correlated with functional CSA and fatty degeneration of MM, which was moderately correlated with clinical outcomes. Conclusions: Results support the hypothesis that IDD is associated with dysregulation of inflammatory state of local MM, which provides initial evidence that inflammatory dysregulation in paraspinal muscles has the potential for a broad impact on tissue health and LBP symptoms.

Dual cation-modified hierarchical nickel hydroxide nanosheet arrays as efficient and robust electrocatalysts for the urea oxidation reaction.

The rational modification of electronic structures to create catalytically active sites has been proved to be a promising strategy to efficiently facilitate the urea oxidation reaction (UOR). Herein, a well-defined nanosheet arrays catalyst of Ni(OH)2 doped with dual cations of Co and Mn on Ni foam (NF) (Co/Mn-Ni(OH)2) is synthesized through a simple hydrothermal process. Benefiting from the advantages of unique structures and modified binding strengths, it is found experimentally that the obtained Co/Mn-Ni(OH)2 catalyst only requires a potential of 1.38 V to deliver a current density of 100 mA cm-2 and exhibits a small Tafel slope of 35 mV dec-1, outperforming single-component-incorporated Ni(OH)2. Moreover, the catalyst has shown excellent stability for 25 h at a current density of 50 mA cm-2. Additionally, first-principles calculations demonstrate that the co-incorporation of Co and Mn remarkably lowers the adsorption barrier of CO(NH2)2* on the catalyst surface, and accelerates the dissociation of the CO(NH2)2* intermediate into CO* and NH* intermediates, which synergistically improve the UOR reaction kinetics. This work provides a generic paradigm for designing advanced and effective catalysts toward the UOR.

Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma.

Adjuvant chemotherapy benefits patients with resected pancreatic ductal adenocarcinoma (PDAC), but the compromised physical state of post-operative patients can hinder compliance. Biomarkers that identify candidates for prompt adjuvant therapy are needed. In this prospective observational study, 1,171 patients with PDAC who underwent pancreatectomy were enrolled and extensively followed-up. Proteomic profiling of 191 patient samples unveiled clinically relevant functional protein modules. A proteomics-level prognostic risk model was established for PDAC, with its utility further validated using a publicly available external cohort. More importantly, through an interaction effect regression analysis leveraging both clinical and proteomic datasets, we discovered two biomarkers (NDUFB8 and CEMIP2), indicative of the overall sensitivity of patients with PDAC to adjuvant chemotherapy. The biomarkers were validated through immunohistochemistry on an internal cohort of 386 patients. Rigorous validation extended to two external multicentic cohorts-a French multicentric cohort (230 patients) and a cohort from two grade-A tertiary hospitals in China (466 patients)-enhancing the robustness and generalizability of our findings. Moreover, experimental validation through functional assays was conducted on PDAC cell lines and patient-derived organoids. In summary, our cohort-scale integration of clinical and proteomic data demonstrates the potential of proteomics-guided prognosis and biomarker-aided adjuvant chemotherapy for PDAC.

Comprehensive geriatric assessment to predict adverse events in elderly patients undergoing posterior lumbar fusion surgery.

PURPOSE: Although comprehensive geriatric assessment (CGA) has been used widely, its impact on adverse events in elderly patients has not been fully examined. The present study aimed to investigate the relationships between subcomponents of CGA and adverse events (AEs) in elderly patients undergoing posterior lumbar fusion surgery. METHODS: A total of 242 eligible elderly patients enrolled. Our CGA included activities of daily living, instrumental activities of daily living, nutritional status, cardiac function, pulmonary function, renal function, frailty, cognition, anxiety, depression, delirium, chronic pain score, comorbidity and polypharmacy. Comprehensive complication index was used to summarize postoperative complications and its severity. Logistic regression was performed to determine the relationships between subcomponents of a CGA and postoperative AEs. RESULTS: Present study found that female were more vulnerable to have AEs. Postoperative major AEs were associated with delirium (odds ratio (OR): 4.302, 95% confidence interval (CI) 1.720-10.761, p = 0.002), nutritional status (OR: 3.030, 95%CI 1.218-7.541, p = 0.017), cognitive impairment (OR: 4.122, 95%CI 1.179-14.407, p = 0.027), Charlson comorbidity index (CCI) (OR: 4.800, 95%CI 1.852-12.440, p = 0.001) and severe dependent (OR: 3.772, 95%CI 1.116-9.841, p = 0.007). Further analysis showed that delirium (OR: 2.824, 95%CI 1.068-7.467, p = 0.036) and CCI (OR: 3.221, 95%CI 1.184-8.766, p = 0.022) were independently related to major AEs. CONCLUSIONS: These results indicate that preoperative screening preoperative delirium, cognitive, nutrition and CCI are essential to prevent postoperative major AEs of the surgical elderly.

Theoretical investigation of asphaltene molecules in crude oil viscoelasticity enhancement.

Understanding the mechanisms of viscosity enhancement in crude oil phases is crucial for optimizing extraction and transportation processes. The enhanced viscosity mechanism of crude oil phase can be attributed to the intricate intermolecular interactions between asphaltene molecules. However, the molecular mechanism of the viscosification of asphaltene molecules in crude oil is not yet to be fully understood. In this work, molecular dynamics simulations were employed to investigate the dynamic behavior and viscosification mechanism of asphaltene molecules in complex oil phases. Research suggests that the neutral surface of asphaltenes features abundant positive and negative electrostatic potential regions, facilitating complementary pairing between these areas. This significantly augments electrostatic interactions among asphaltene molecules. Besides, the expansive nonpolar expanse on the normal asphaltene surface facilitates interactions between asphaltenes and crude oil molecules. This leads the crude oil viscosity of the system containing normal asphaltene is higher than that of the system containing acidic asphaltene under the same mass fraction (382 µ Pa·s for AAsp and 416 µ Pa·s for NAsp). This work provides insight into the viscosity enhancement mechanisms in crude oil phases and is helpful in improving the efficiency of crude oil extraction and transportation.

Treatment of malignant airway stenosis with extracorporeal membrane oxygenation under low-dose anticoagulation: A case report.

The occurrence of airway obstruction due to severe stenosis from lung cancer poses a significant risk of asphyxia. Although the placement of a metallic stent may relieve the obstruction, the procedure is associated with a high risk of asphyxia. To mitigate this risk, extracorporeal membrane pulmonary oxygenation (ECMO) has been proposed to temporarily substitute for cardiopulmonary function during the procedure. However, the use of systemic anticoagulation with heparin during ECMO may increase the likelihood of bleeding during surgery. This case report describes a successful treatment of a patient with malignant central airway obstruction through low-dose heparin veno-venous ECMO. This approach resulted in reduced intraoperative bleeding and invasive operation time, allowing for prompt postoperative withdrawal and recovery.

Association between periodontitis and disc structural failures in patients with cervical degenerative disorders.

OBJECTIVE: Recent studies have shown that the mouth-gut-disc axis may play a key role in the process of disc structural failures (including intervertebral disc degeneration (IDD) and endplate change) in the cervical spine and neck pain. However, the potential mechanisms underlying the mouth-gut-disc axis remain elusive. Therefore, we explored whether periodontal disease is associated with disc structural failures in patients with cervical degeneration disorders and clinical outcomes. METHODS: Adults (aged > 18 years) who met open surgery criteria for cervical spine were enrolled in this prospective cohort study. Participants were allocated into two groups based on periodontal examinations before surgery: no/mild periodontitis group and moderate/severe periodontitis group. Data were evaluated using an independent t test and Pearson's correlation analysis. RESULTS: A total of 108 patients were enrolled, including 68 patients in the no/mild periodontitis group and 40 patients in the moderate/severe periodontitis group. The number of common causes of missing teeth (P = 0.005), plaque index (PLI) (P = 0.003), bleeding index (BI) (P = 0.000), and probing depth (PD) (P = 0.000) significantly differed between the two groups. The incidence rate of endplate change (P = 0.005) was higher in the moderate/severe periodontitis group than in the no/mild periodontitis group. A moderate negative association was found between the neck disability index (NDI) score and periodontal parameters (PLI: r = - 0.337, P = 0.013; BI: r = - 0.426, P = 0.001; PD: r = - 0.346, r = - 0.010). CONCLUSIONS: This is the first study to provide evidence that severe periodontitis is associated with a higher occurrence rate of disc structural failures and poor clinical outcomes in patients with cervical degenerative disorders.

Enhanced Recovery After Surgery (ERAS) Program for Anterior Cervical Discectomy and Fusion (ACDF) in Patients Over 60 Years Old.

Background: Enhanced recovery after surgery (ERAS) is currently widely used in many surgical specialties, but there is still a lack of concern about the cervical ERAS program for old patients (>60 years old). We aimed to determine whether our ERAS program significantly improved satisfaction and outcomes in old patients (>60 years old) with anterior cervical discectomy and fusion (ACDF). Methods: This is a retrospective cohort study. The study enrolled patients if they were over the age of 60 years old underwent ACDF from July 2019 and June 2021 (ERAS group) and from January 2018 and June 2019 (non-ERAS group). Data including demographic, comorbidity, and surgical information were collected. We also evaluated ERAS process compliance, primary outcome, surgical complication, and length of stay (LOS). Results: There were 135 patients in the ERAS group, and 122 patients in the non-ERAS group were included. A comparison of the demographic data revealed that there were no statistically significant intergroup differences observed between the group. Overall, ERAS pathway compliance was 91.9%. There were no significant differences in the fusion levels, operative time, intraoperative blood loss, postoperative VAS score, and complications between the ERAS and non-ERAS groups. In addition, there was no significant difference in readmission and mortality at 30-day follow-up between the two groups. However, we observed a statistically significant decrease in the LOS in the ERAS group (8.68±2.34 of ERAS group versus 10.43±4.05 in non-ERAS group, p=0.013). Conclusion: This report describes the first ERAS protocol used in old patients with ACDF. Our ERAS program is safe and associated with incremental benefits with respect to LOS in old patients with ACDF.

miR-4780 Derived from N2-Like Neutrophil Exosome Aggravates Epithelial-Mesenchymal Transition and Angiogenesis in Colorectal Cancer.

Despite significant advances in diagnostic methods and treatment strategies, the prognosis for patients with advanced colon cancer remains poor, and mortality rates are often high due to metastasis. Increasing evidence showed that it is of significant importance to investigate how the tumor microenvironment participates in the development of colorectal cancer (CRC). In this manuscript, neutrophils were sequentially stimulated with all-trans retinoic acid and transforming growth factor-ß in turn to induce the neutrophil polarization. Differentially expressed miRNA in neutrophil exosomes have been sequenced by microarray profile, and the effect of N2-like neutrophil-derived exosomal miR-4780 on epithelial-mesenchymal transition (EMT) and angiogenesis was investigated. In our results, we found that neutrophils were enriched in CRC tumor tissue and that CD11b expression correlated with tumor site and serous membrane invasion. At the same time, we demonstrated that internalization of N2 exosomes exacerbated the viability, migration, and invasion of CRC cell lines and inhibited apoptosis. To further investigate the molecular mechanism, we analyzed the miRNA expression profile in the N2-like neutrophils, which led to the selection of hsa-miR-4780 for the subsequent experiment. The overexpression of miR-4780 from N2-like neutrophil-derived exosomes exacerbated EMT and angiogenesis. Moreover, miR-4780 can regulate its target gene SOX11 to effect EMT and angiogenesis in CRC cell lines. CRC with liver metastasis model also validated that aberrant expression of miR-4780 in N2-like neutrophil exosomes exacerbated tumor metastasis and development of tumor via EMT and angiogenesis. In conclusion, our current findings reveal an important mechanism by which mR-4780 from N2-like neutrophil exosomes exacerbates tumor metastasis and progression via EMT and angiogenesis.

Distribution of bone tunnel positions and treatment efficacy of bone landmark positioning method for anatomical reconstruction of the anterior cruciate ligament: a case control study.

BACKGROUND: This study aimed to investigate the distribution of femoral tunnel and explore the influences of bone tunnel positions on knee functions. The bone landmark positioning method was used to position the femoral tunnel during the anatomical reconstruction surgery in patients with anterior cruciate ligament (ACL) rupture. METHODS: Data of patients who underwent anatomical reconstruction of the ACL between January 2015 and July 2018, were retrospectively analyzed. The distribution of the femoral tunnel was recorded on 3-D CT after surgery. The tunnel positions were classified into good and poor position groups based on whether the position was in the normal range (24-37% on the x-axis and 28-43% on the y-axis). The Lysholm and IKDC scores, KT-1000 side-to-side difference, pivot shift test and Lachman test results of the knee joints were recorded, and then the differences in knee joint functions between the two groups were analyzed. RESULTS: 84 eligible patients (84 knees) were finally included in this study. Twenty-two and 62 of the patients were categorized in the good and poor position groups, respectively, and the rate of good position was 26.2%. The distribution of bone tunnel was as follows: (x-axis) deep position in 10 patients (12%), normal position in 58 patients (69%), and shallow position in 16 patients (19%); (y-axis) high position in 54 patients (64%), normal position in 26 patients (31%), and low position in 4 patients (5%). 1 year later, the Lysholm and IKDC scores were significantly better in the good position group (P < 0.05), the KT-1000 side to side difference, the pivot shift test and Lachman test results were better in the good position group (P < 0.05). CONCLUSIONS: The bone tunnels were found to be distributed in and beyond the normal range using the bone landmark method to position the femoral tunnel in the single-bundle anatomical reconstruction of ACL, while the rate of good bone tunnel position was low. The knee joint function scores and stability were lower in patients with poor position of the femoral tunnel.

Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology.

Organoid models have the potential to recapitulate the biological and pharmacotypic features of parental tumors. Nevertheless, integrative pharmaco-proteogenomics analysis for drug response features and biomarker investigation for precision therapy of patients with liver cancer are still lacking. We established a patient-derived liver cancer organoid biobank (LICOB) that comprehensively represents the histological and molecular characteristics of various liver cancer types as determined by multiomics profiling, including genomic, epigenomic, transcriptomic, and proteomic analysis. Proteogenomic profiling of LICOB identified proliferative and metabolic organoid subtypes linked to patient prognosis. High-throughput drug screening revealed distinct response patterns of each subtype that were associated with specific multiomics signatures. Through integrative analyses of LICOB pharmaco-proteogenomics data, we identified the molecular features associated with drug responses and predicted potential drug combinations for personalized patient treatment. The synergistic inhibition effect of mTOR inhibitor temsirolimus and the multitargeted tyrosine kinase inhibitor lenvatinib was validated in organoids and patient-derived xenografts models. We also provide a user-friendly web portal to help serve the biomedical research community. Our study is a rich resource for investigation of liver cancer biology and pharmacological dependencies and may help enable functional precision medicine.

Endoscopic Suture With Chemocauterization: An Effective Treatment of Congenital Pyriform Sinus Fistula.

OBJECTIVE: Endoscopic cauterization is an effective method for treating pyriform sinus fistula (PSF). However, these approaches sometimes result in a higher failure rate. We present an effective technique utilizing suture combined with chemocauterization as first-line treatment in patients with PSF and evaluate the safety and efficacy of its use in 126 patients. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. METHODS: Retrospective case review of patients treated between March 2012 and June 2021 at our institution with descriptive statistical analysis. RESULTS: A total of 126 patients with PSF were included in this study with a mean age of 14.7 years. There was no sex predilection. The majority of patients presented with a left-sided neck lesion (89.7%). Ten patients presented following prior attempts at the surgery of the PSF at another institution; 8 via open surgery and 2 following endoscopic CO2 laser cauterization; other patients only had a history of repeat incision and drainage or antibiotic treatment. The success rate of obliteration of the internal opening was 96.83% after a single treatment without complications. Following reoperation, a successful outcome was achieved in the remaining 4 patients. Length of stay ranged from 10 to 14 days. No recurrences occurred within 12 to 120 months followed-up. CONCLUSION: Endoscopic suture combined with chemocauterization is a safe and effective treatment of PSF. Surgery can be performed during the acute cervical inflammatory period without increased risk of complication or recurrence, however, patients found to have acute changes affecting the pyriform sinus should be treated with a staged surgery strategy.

Preventive Effect of Local Lidocaine Administration on the Formation of Traumatic Neuroma.

BACKGROUND: Traumatic neuroma is a common sequela of peripheral nerve injury or amputation, which often leads to severe neuropathic pain. The present study investigated the effect of local lidocaine administration on preventing the formation of traumatic neuroma. METHODS: Forty-eight male Sprague-Dawley rats were randomly assigned to two groups. The lidocaine group underwent sciatic nerve transection, followed by an injection of lidocaine (0.5%) around the proximal of a severed sciatic nerve under ultrasound-guidance 2-7 days after neurectomy. In the control group, rats received an injection of saline following neurectomy. The autotomy score, mechanical allodynia, thermal hyperalgesia, histological assessment, expression of neuroma, and pain-related markers were detected. RESULTS: Lidocaine treatment reduced the autotomy score and attenuated mechanical allodynia and thermal hyperalgesia. The mRNA expression of α-SMA, NGF, TNF-α, and IL-1ß all significantly decreased in the lidocaine group in comparison to those in the saline control group. The histological results showed nerve fibers, demyelination, and collagen hyperplasia in the proximal nerve stump in the saline control group, which were significantly inhibited in the lidocaine group. CONCLUSIONS: The present study demonstrated that local lidocaine administration could inhibit the formation of painful neuroma due to traumatic nerve injury.