Human platelet lysate-cultured adipose-derived stem cell sheets promote angiogenesis and accelerate wound healing via CCL5 modulation.

BACKGROUND: A rising population faces challenges with healing-impaired cutaneous wounds, often leading to physical disabilities. Adipose-derived stem cells (ASCs), specifically in the cell sheet format, have emerged as a promising remedy for impaired wound healing. Human platelet lysate (HPL) provides an attractive alternative to fetal bovine serum (FBS) for culturing clinical-grade ASCs. However, the potential of HPL sheets in promoting wound healing has not been fully investigated. This study aimed to explore the anti-fibrotic and pro-angiogenic capabilities of HPL-cultured ASC sheets and delve into the molecular mechanism. METHODS: A rat burn model was utilized to evaluate the efficacy of HPL-cultured ASC sheets in promoting wound healing. ASC sheets were fabricated with HPL, and those with FBS were included for comparison. Various analyses were conducted to assess the impact of HPL sheets on wound healing. Histological examination of wound tissues provided insights into aspects such as wound closure, collagen deposition, and overall tissue regeneration. Immunofluorescence was employed to assess the presence and distribution of transplanted ASCs after treatment. Further in vitro studies were conducted to decipher the specific factors in HPL sheets contributing to angiogenesis. RESULTS: HPL-cultured ASC sheets significantly accelerated wound closure, fostering ample and organized collagen deposition in the neo-dermis. Significantly more retained ASCs were observed in wound tissues treated with HPL sheets compared to the FBS counterparts. Moreover, HPL sheets mitigated macrophage recruitment and decreased subsequent wound tissue fibrosis in vivo. Immunohistochemistry also indicated enhanced angiogenesis in the HPL sheet group. The in vitro analyses showed upregulation of C-C motif chemokine ligand 5 (CCL5) and angiogenin in HPL sheets, including both gene expression and protein secretion. Culturing endothelial cells in the conditioned media compared to media supplemented with CCL5 or angiogenin suggested a correlation between CCL5 and the pro-angiogenic effect of HPL sheets. Additionally, through neutralizing antibody experiments, we further validated the crucial role of CCL5 in HPL sheet-mediated angiogenesis in vitro. CONCLUSIONS: The present study underscores CCL5 as an essential factor in the pro-angiogenic effect of HPL-cultured ASC sheets during the wound healing process. These findings highlight the potential of HPL-cultured ASC sheets as a promising therapeutic option for healing-impaired cutaneous wounds in clinical settings. Furthermore, the mechanism exploration yields valuable information for optimizing regenerative strategies with ASC products. BRIEF ACKNOWLEDGMENT: This research was supported by the National Science and Technology Council, Taiwan (NSTC112-2321-B-002-018), National Taiwan University Hospital (111C-007), and E-Da Hospital-National Taiwan University Hospital Joint Research Program (111-EDN0001, 112-EDN0002).

Dislodgment Effects of Different Cage Arrangements in Posterior Lumbar Interbody Fusion: A Finite Element Study.

The vertebral cage has been widely used in posterior lumbar interbody fusion. The risk of cage dislodgment is high for patients undergoing lumbar fusion surgery. Therefore, the main objective of this study was to use a lumbar fusion model to investigate the effects of cage dislodgment on different cage arrangements after PLIF. Finite element analysis was used to compare three PEEK cage placements, together with the fibula-type cage, with respect to the four kinds of lumbar movements. The results revealed that a horizontal cage arrangement could provide a better ability to resist cage dislodgment. Overall lumbar flexion movements were confirmed to produce a greater amount of cage slip than the other three lumbar movements. The lower part of the lumbar fusion segment could create a greater amount of cage dislodgment for all of the lumbar movements. Using an autograft with a fibula as a vertebral cage cannot effectively reduce cage dislodgment. Considering the maximum movement type in lumbar flexion, we suggest that a horizontal arrangement of the PEEK cage might be considered when a single PEEK cage is placed in the fusion segment, as doing so can effectively reduce the extent of cage dislodgment.

Dorsal spanning plating for complex carpometacarpal fracture-dislocations: a retrospective case series.

We studied the outcome of dorsal spanning plate for complex carpometacarpal fracture-dislocation management as a feasible option in nine patients, even on delayed presentation with substantial metacarpal shortening. However, patients must be informed about the need for plate removal.

Direct Photocatalytic Methane Oxidation to Formaldehyde by N Doping Co-Decorated Mixed Crystal TiO2.

In this paper, N-doped TiO2 mixed crystals are prepared via direct calcination of TiN for highly selective oxidation of CH4 to HCHO at room temperature. The structures of the prepared TiO2 samples are characterized to be N-doped TiO2 of anatase and rutile mixed crystals. The crystal structures of TiO2 samples are determined by XRD spectra and Raman spectra, while N doping is demonstrated by TEM mapping, ONH inorganic element analysis, and high-resolution XPS results. Significantly, the production rate of HCHO is as high as 23.5 mmol·g-1·h-1 with a selectivity over 90%. Mechanism studies reveal that H2O is the main oxygen source and acts through the formation of ·OH. DFT calculations indicate that the construction of a mixed crystal structure and N-doping modification mainly act by increasing the adsorption capacity of H2O. An efficient photocatalyst was prepared by us to convert CH4 to HCHO with high yield and selectivity, greatly promoting the development of the photocatalytic CH4 conversion study.

Nerve bypass surgery for spinal cord reconstruction.

OBJECTIVE: Spinal cord injury (SCI) is a devastating condition that significantly decreases the patient's quality of life. Therefore, treatments that can facilitate nerve regeneration, reduce complications, and increase quality of life are valuable for these patients. In this study, we aimed to assess nerve bypass surgery's feasibility and clinical outcomes by transferring the intercostal nerves (ICNs) into the spinal cord. METHODS: Eight patients with complete thoracic SCI and delayed presentation more than a year after the injury were analyzed retrospectively. All patients underwent nerve bypass surgery with the transfer of two pairs of ICNs from proximal to the injury site to the anterolateral spinal cord, followed by duraplasty with fascia grafting to close the dura. RESULTS: Six of the eight (75%) patients demonstrated motor and sensory improvements, based on the American Spinal Cord Injury Association score. Three patients demonstrated a limited recovery of motor function that could be independently triggered without ICN initiation. Five patients demonstrated evidence of cerebrospinal fluid (CSF) leakage after surgery; however, only one patient complained of a headache. CONCLUSION: Spinal cord bypass surgery is a potential reconstruction method to treat chronic complete thoracic SCI with functional improvements, and is worth further investigation.

Advancing surgical VQA with scene graph knowledge.

PURPOSE: The modern operating room is becoming increasingly complex, requiring innovative intra-operative support systems. While the focus of surgical data science has largely been on video analysis, integrating surgical computer vision with natural language capabilities is emerging as a necessity. Our work aims to advance visual question answering (VQA) in the surgical context with scene graph knowledge, addressing two main challenges in the current surgical VQA systems: removing question-condition bias in the surgical VQA dataset and incorporating scene-aware reasoning in the surgical VQA model design. METHODS: First, we propose a surgical scene graph-based dataset, SSG-VQA, generated by employing segmentation and detection models on publicly available datasets. We build surgical scene graphs using spatial and action information of instruments and anatomies. These graphs are fed into a question engine, generating diverse QA pairs. We then propose SSG-VQA-Net, a novel surgical VQA model incorporating a lightweight Scene-embedded Interaction Module, which integrates geometric scene knowledge in the VQA model design by employing cross-attention between the textual and the scene features. RESULTS: Our comprehensive analysis shows that our SSG-VQA dataset provides a more complex, diverse, geometrically grounded, unbiased and surgical action-oriented dataset compared to existing surgical VQA datasets and SSG-VQA-Net outperforms existing methods across different question types and complexities. We highlight that the primary limitation in the current surgical VQA systems is the lack of scene knowledge to answer complex queries. CONCLUSION: We present a novel surgical VQA dataset and model and show that results can be significantly improved by incorporating geometric scene features in the VQA model design. We point out that the bottleneck of the current surgical visual question-answer model lies in learning the encoded representation rather than decoding the sequence. Our SSG-VQA dataset provides a diagnostic benchmark to test the scene understanding and reasoning capabilities of the model. The source code and the dataset will be made publicly available at: https://github.com/CAMMA-public/SSG-VQA .

The long-term outcomes and prognostic factors about locally advanced right colon cancer: a retrospective cohort study.

Background: The first case of treatment with en bloc right hemicolectomy with pancreatoduodenectomy (RHCPD) for locally advanced right-sided colon cancer (LARCC) invading the pancreas, duodenum, or other organs, was reported in 1953 by Van Prohaska. Right-sided colon cancers invading the pancreas and duodenum are rare. Surgery can be technically challenging, with unclear oncologic consequences, hence there are few reports on the clinical outcomes and factors associated with survival in this patient cohort. The need for neoadjuvant chemotherapy in patients with LARCC is controversial, and the long-term survival of these patients as well as the preferred treatment regimen needs to be explored. This paper reports our experience in right hemicolectomy with en bloc resection for LARCC. We conducted this study to analyze the clinical features and surgical outcomes of LARCC. Methods: A retrospective study was performed using a database of all patients who underwent RHCPD due to the tumour directly invading the duodenum and/or pancreas in a 19-year period [2003-2022]. We included patients whose primary tumor site was the right hemicolon and who had undergone a negative tumor resection margin (R0) resection. In addition, the adhesions between the colon and other organs in these patients were malignant adhesions. The primary outcome was the overall survival after surgery. The secondary endpoints of the study included 30-day postoperative mortality, postoperative complications, prognostic factors, and tumour genetics. All patients were followed up with postoperative imaging at an interval of 3 months for the first 3 years and at an interval of 6 months for the next 2 years, and annual follow-up thereafter. Survival was estimated using Kaplan-Meier analysis. Variables with P values <0.05 in univariate analysis were entered into multivariate Cox proportional risk regression to identify independent predictors of survival. Results: There were 47 patients (23 males and 24 females) who underwent en bloc resection for LARCC. The median age of the patients was 61 years (range, 38-80 years). R0 resection was achieved in all cases. The overall complication rate was 27.7% (n=13). Two patients died within 30 days of surgery. The overall survival was 80.9%, 63.5%, and 51.7% at 1, 3, and 5 years, respectively. Univariate survival analysis identified pancreatic invasion, regional lymph node positivity, more than two organs invaded, and no neoadjuvant treatment as predictors of poor survival (log-rank P<0.05). Multivariate analysis showed that regional lymph node positivity [95% confidence interval (CI): 1.145-7.736; P=0.025] and more than two organs invaded (95% CI: 1.321-26.981; P=0.020) were predictors of poor survival. Conclusions: Relatively optimistic clinical outcomes from en bloc resection were demonstrated for patients with LARCC. For LARCC patients, en bloc resection can be carefully considered.

Synergistic regulation of chloride anion recognition using a triple-functional sites receptor with two different cationic effectors.

The synergistic regulation of the multi-functional sites on one receptor molecule with different cationic effectors for anion recognition is scarce to be well understood from the experiment and theory. In this work, a new anion receptor with three functional zones including ether hole, biurea and double bipyridine groups (EUPR) is designed expecting to enhance the chloride anion recognition together with a rational synthesis path being proposed based on four simple and mature organic reaction steps. The conformational structures of the designed receptor EUPR and the binding behaviors for three kinds of ions (Cl-, Na+, and Ag+) are deeply investigated by using density functional theoretical calculations. It is found that Cl- binding via the hydrogen bond interaction can be significantly enhanced and synergistically regulated by the two kinds of cations and the corresponding conformational changes of receptor EUPR. Especially, the conformational pre-organization of receptor caused by the encapsulation of sodium ion into ether hole is benefit to the binding for Cl- in both thermodynamics and kinetics. Na+ binding, in turn, can ever be enhanced by chloride anion, whereas it seems that Ag+ binding cannot always be enhanced by chloride anion, reflecting an electrical complementary matching and mutual enhancement effect for different counter ions. Moreover, solvent effect calculations indicate that EUPR may be an ideal candidate structure for Cl- recognition by strategy of counter ion enhancement in water. Additionally, a visual study of intermolecular noncovalent interaction (NCI) and molecular electrostatic potential (ESP) are used for the analysis on the nature of interactions between receptor and bound ions.

Best practices for managing malodorous and infected wounds in advanced cervical cancer.

This cross-sectional study was conducted to examine the most effective strategies for managing malodorous and infected wounds in patients who have been diagnosed with advanced cervical cancer. The research was conducted in Liupanshui, China. The study specifically examined demographic profiles, wound characteristics and effectiveness of wound management approaches. The study incorporated the heterogeneous sample of 289 participants who fulfilled the inclusion criteria. Data collection was conducted via structured questionnaires and medical record evaluations. Descriptive statistics and statistical analyses, such as regression analysis, were utilized to evaluate demographic attributes, wound profiles and effects of different approaches to wound management. The findings unveiled the heterogeneous demographic composition of patients, encompassing differences in socioeconomic standing, educational attainment and age. A wide range of wound characteristics were observed, as 65.7% of lesions during the acute phase with diameter between 2 and 5 centimetres, while 41.5% of lesions had this range. The most prevalent types of infections were those caused by fungi (48.4%), followed by bacterial infections lacking resistance (38.1%). A moderate degree of odour intensity was prevalent, affecting 45.0% of the cases. With maximal odour reduction of 80%, a mean healing time of 25 days and patient satisfaction rating of 4.5 out of 5, Negative Pressure Wound Therapy demonstrated itself to be the most efficacious treatment method. Additional approaches, such as photodynamic therapy and topical antibiotic therapy, demonstrated significant effectiveness, as evidenced by odour reductions of 70% and 75%, respectively, and patient satisfaction ratings of 4.3 and 4.2. Thus, the study determined challenges associated with management of malodorous and infected lesions among patients with advanced cervical cancer. The results underscored the significance of individualized care approaches, drew attention to efficacious wound management techniques and identified critical determinants that impacted patient recuperation. The findings of this study hold potential for advancing palliative care for individuals diagnosed with advanced cervical cancer.

Interim Use of Antibiotic-Loaded Cement Spacer for Patients with Infected Cervical Fusion.

OBJECTIVE: The management of postoperative deep infection after anterior cervical discectomy and fusion (ACDF) remains challenging for spine surgeons. Our institution uses handmade antibiotic-loaded cement spacers to treat these complex cases. This study aimed to determine the efficacy and feasibility of this treatment. METHODS: This study included 4 patients with deep cervical spine infections after ACDF who underwent our treatment between March 2012 and January 2022. Patients' laboratory data, visual analog scale scores, comorbidities, complications, and neurological status were recorded. Their clinical conditions were also evaluated based on the Neck Disability Index, Japanese Orthopaedic Association score, and Odom criteria. RESULTS: Infection eradication was achieved in all patients after treatment. The average preoperative visual analog scale score was 7.5 (range: 7-8); this decreased to 1.25 (range: 1-2) at 1 year postoperatively. None of the patients experienced severe complications, such as neurological deterioration or bone graft dislodgement. The Neck Disability Index improved from a preoperative value of 54% (range: 48-60%) to 6% (range: 4-8%) at 1 year postoperatively. The Japanese Orthopaedic Association score improved from a preoperative score of 10.25 (range: 10-11)-14.75 (range: 14-16) at 1 year postoperatively. All patients achieved excellent outcomes based on Odom criteria at 1 year postoperatively. CONCLUSIONS: Good clinical outcomes were achieved in this study. Although 2-stage surgery is required, this technique could be an alternative for patients with postoperative deep infection after ACDF.

Use of Technetium-99m-Pyrophosphate Single-Photon Emission Computed Tomography/Computed Tomography in Monitoring Therapeutic Changes of Eplontersen in Patients With Hereditary Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: Hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) is a progressive and fatal disease. Recent evidence indicates that bone scintigraphy may serve as a tool to monitor the effectiveness of hATTR-CM treatment. The objective of this study was to examine how eplontersen therapy influences the semiquantitative uptake of technetium-99m-pyrophosphate in individuals diagnosed with hATTR-CM. METHODS AND RESULTS: We retrospectively analyzed a prospective cohort from the NEURO-TTRansform trial, including patients with hATTR-CM receiving eplontersen (45 mg/4 weeks). A control group comprised patients with hATTR-CM who had not received eplontersen, inotersen, tafamidis, or patisiran. Technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography was conducted at baseline and during follow-up. Thirteen patients with hATTR-CM were enrolled, with 6 receiving eplontersen and 7 serving as the control group. The median follow-up time was 544 days. The eplontersen group exhibited a significant decrease in volumetric heart and lung ratio (3.774 to 2.979, P=0.028), whereas the control group showed no significant change (4.079 to 3.915, P=0.237). Patients receiving eplontersen demonstrated a significantly greater reduction in volumetric heart and lung ratio compared with the control group (-20.7% versus -3.4%, P=0.007). CONCLUSIONS: The volumetric heart and lung ratio used to quantify technetium-99m-pyrophosphate uptake showed a significant reduction subsequent to eplontersen treatment in individuals diagnosed with hATTR-CM. These findings suggest the potential efficacy of eplontersen in treating hATTR-CM and highlight the value of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography as a tool for monitoring therapeutic effectiveness.

DNA Logical Device Combining an Entropy-Driven Catalytic Amplification Strategy for the Simultaneous Detection of Exosomal Multiplex miRNAs In Situ.

Exosomal miRNAs are considered promising biomarkers for cancer diagnosis, but their accuracy is severely compromised by the low content of miRNAs and the large amount of exosomal miRNAs released from normal cells. Here, we presented a dual-specific miRNA's logical recognition triggered by an entropy-driven catalysis (EDC)-enhanced system in exosomes for accurate detection of liver cancer-cell-derived exosomal miR-21 and miR-122. Taking advantage of the accurate analytical performance of the logic device, the excellent membrane penetration of gold nanoparticles, and the outstanding amplification ability of the EDC reaction, this method exhibits high sensitivity and selectivity for the detection of tumor-derived exosomal miRNAs in situ. Moreover, due to its excellent performance, this logic device can effectively distinguish liver cancer patients from healthy donors by determining the amount of cancer-cell-derived exosomal miRNAs. Overall, this strategy has great potential for analyzing various types of exosomes and provides a viable tool to improve the accuracy of cancer diagnosis.

Tafamidis improves myocardial longitudinal strain in A97S transthyretin cardiac amyloidosis.

Background: Transthyretin cardiomyopathy (ATTR-CM) is a debilitating disease that has received much attention since the emergence of novel treatments. The Transthyretin Cardiomyopathy Clinical Trial showed that tafamidis, a transthyretin tetramer stabilizer, effectively reduced the declines in functional capacity and quality of life. However, Ala97Ser (A97S) hereditary ATTR-CM is underrepresented in major ATTR-CM tafamidis trials. Objectives: We aim to investigate the change in global longitudinal strain (GLS) of A97S ATTR-CM patients after 12 months of tafamidis treatment. Methods: We retrospectively analysed a prospective cohort of patients with A97S ATTR-CM who received tafamidis meglumine (61 mg/day) at the National Taiwan University Hospital. Echocardiography with speckle tracking strain analysis was performed at baseline and 12 months after treatment. Results: In all, 20 patients were included in the cohort. The baseline left ventricular ejection fraction (LVEF) and interventricular septum (IVS) thickness were 59.20 ± 13.23% and 15.10 ± 3.43 mm, respectively. After 12 months of tafamidis treatment, the LVEF and IVS were 61.83 ± 15.60% (p = 0.244) and 14.59 ± 3.03 mm (p = 0.623), respectively. GLS significantly improved from -12.70 ± 3.31% to -13.72 ± 3.17% (p = 0.048), and longitudinal strain (LS) in apical and middle segments significantly improved from -16.05 ± 4.82% to -17.95 ± 3.48% (p = 0.039) and -11.89 ± 4.38% to -13.58 ± 3.12% (p = 0.039), respectively. Subgroup analysis showed that patients with LVEF < 50% had a better treatment response and improvement in GLS. The patients with an IVS ⩾ 13 mm had an improvement in two-chamber LS from -10.92 ± 4.25% to -13.15 ± 3.87% (p = 0.042) and an improvement in apical left ventricular LS from -15.30 ± 5.35% to -17.82 ± 3.99% (p = 0.031). Conclusion: Tafamidis significantly improved GLS, and particularly apical and middle LS in A97S ATTR-CM patients.

Tafamidis improves myocardial longitudinal strain in A97S transthyretin cardiac amyloidosis Transthyretin cardiomyopathy (ATTR-CM) is a severe heart condition that has gained attention due to recent advancements in treatments. One of these treatments, called tafamidis, has been shown to be effective in maintaining heart function and quality of life. However, there has been limited research on a specific genetic variation of ATTR-CM: A97S. Our aim was to determine whether A97S ATTR-CM patients experienced improved heart function after one year of tafamidis treatment. We conducted this study at the National Taiwan University Hospital, where we enrolled 20 A97S ATTR-CM patients. We used echocardiography to evaluate their heart function, focusing on a parameter called global longitudinal strain. The results showed that after one year of tafamidis treatment, these patients experienced a significant improvement in their global longitudinal strain, particularly in the apical and middle regions of the heart. In conclusion, tafamidis appears to be beneficial for A97S ATTR-CM patients by enhancing their heart's global longitudinal strain, which is a positive sign for their cardiac health.

First 100 total hip arthroplasties performed by a young surgeon using the direct anterior approach: learning curve and complications.

INTRODUCTION: Most of the reported discussions about the learning curve for the direct anterior approach (DAA) in total hip arthroplasty (THA) have been by experienced surgeons. The study's aim was to describe the learning curve, short-term outcomes, complications, and adaptations to the DAA used in the first 100 THA cases experienced by a young surgeon who had received DAA training for trauma surgeries. MATERIALS AND METHODS: This retrospective study summarizes the first 100 consecutive cases experienced by a young surgeon who performed the unilateral DAA for THA between 2019 and 2021. Cumulative sum (CUSUM) analysis was performed to evaluate the learning curve on the basis of operative time and overall complications. The demographics data, short-term outcomes, and complications of the first 50 and second 50 cases were compared. RESULTS: The CUSUM curve declined after 49 and 55 cases, measured by operative time and overall complications, respectively. The median operative time (104 vs. 80 min) and intraoperative fluoroscopic time (38 vs. 12 s) increased significantly in the first 50 cases compared with the times in the second 50 cases. Complications tended to occur in the first 50 cases (12% vs. 6%), and the overall rate was 9%. Major complications all occurred in the first 50 cases, with a rate of 4%. Only one case, which involved a complicated periprosthetic fracture around the stem that extended to the tip, required the intervention of a senior surgeon. CONCLUSIONS: Even after receiving training on the DAA for trauma surgeries, the young surgeon experienced a steep learning curve and more complications in the first 50 cases. The DAA for THA is a technically demanding procedure and may require guidance from an experienced surgeon to manage unexpected complications.

The relationship between GLIM-malnutrition, post-operative complications and long-term prognosis in elderly patients undergoing colorectal cancer surgery.

Background: Elderly people and patients with colorectal cancer (CRC) are both at high risk of malnutrition. Therefore, it is of great significance to explore suitable malnutrition screening and diagnostic indicators for elderly patients with CRC. Recently, the Global Leadership Initiative on Malnutrition (GLIM) proposed new diagnostic criteria for malnutrition. The aim of this article was to evaluate the diagnostic value of GLIM criteria for malnutrition in elderly colorectal patients. We explored the relationship between GLIM-malnutrition, post-operative complications and the long-term prognosis of elderly colorectal patients. Methods: Elderly patients (aged ≥65 years) who underwent CRC surgery from January 2015 to December 2018 were included. Malnutrition was diagnosed based on the GLIM criteria. The relationships between GLIM-malnutrition and clinical characteristics were analyzed by t-tests, Mann-Whitney U tests, and chi-squared tests. The relationships between GLIM-malnutrition and post-operative complications were analyzed by chi-squared tests, and logistic regression analyses. The relationships between GLIM-malnutrition and the long-term prognosis were analyzed by Kaplan-Meier analyses and logistic and Cox regression analyses. Results: A total of 385 elderly patients were included in this study, and 118 patients (30.65%) were diagnosed with malnutrition according to the GLIM criteria. GLIM-malnutrition was significantly associated with older age, lower body mass index (BMI), lower grip strength, tumor location, higher Nutrition Risk Screening 2002 (NRS-2002), and lower levels of albumin and hemoglobin. GLIM-malnutrition was an independent risk factor [odds ratio (OR): 1.753, 95% confidence interval (CI): 1.100-2.795, P=0.018] for post-operative complications. Cox regression analysis showed that GLIM-malnutrition was an independent risk factor for overall survival in elderly patients with CRC. Conclusions: The GLIM criteria are feasible diagnostic criteria for malnutrition of elderly patients with CRC. GLIM-malnutrition is significantly associated with post-operative complications and overall survival in elderly patients with CRC.

Tafamidis decreased cardiac amyloidosis deposition in patients with Ala97Ser hereditary transthyretin cardiomyopathy: a 12-month follow-up cohort study.

BACKGROUND: Transthyretin cardiac cardiomyopathy (ATTR-CM) is a rare but life-threatening disease. Tafamidis is an effective treatment for patients with ATTR-CM, however its long-term effects on cardiac remodeling and cardiac amyloid deposition are unknown. This study aimed to used cardiac magnetic resonance (CMR) to investigate the effects of tafamidis on patients with hereditary A97S ATTR-CM. METHODS: We retrospectively analyzed a prospective cohort of ATTR-CM patients, including 14 with hereditary A97S ATTR-CM and 17 healthy controls with baseline CMR data. All ATTR-CM patients received tafamidis treatment and received CMR with extracellular volume (ECV) at baseline and after 1 year of follow-up. RESULTS: Baseline N-terminal pro-B-type natriuretic peptide, left ventricular (LV) mass, LV ejection fraction, global radial, circumferential and longitudinal strain, T1 mapping and ECV were significantly worse in the patients with ATTR-CM compared with the healthy controls. After 1 year of tafamidis treatment, ECV decreased from 51.5 ± 8.9% to 49.0 ± 9.4% (P = 0.041), however there were no significant changes in LV mass, LV ejection fraction, global radial strain, global circumferential strain, global longitudinal strain and T1 mapping. CONCLUSIONS: After a one-year treatment period, tafamidis exhibited subtle but statistically significant reductions in ECV, potentially indicating a decrease in amyloid deposition among patients diagnosed with hereditary A97S ATTR-CM.

Adjuvant Lenvatinib Plus PD-1 Antibody for Hepatocellular Carcinoma with High Recurrence Risks After Hepatectomy: A Retrospective Landmark Analysis.

Purpose: To evaluate the efficacy and safety of lenvatinib plus programmed death-1 (PD-1) antibody as postoperative adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risks of recurrence. Patients and Methods: A series of 137 patients with HCC at high risks of recurrence who underwent hepatectomy at our hospital between October 2019 and January 2022 were retrospectively analyzed. Recurrence-free survival (RFS), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed. Landmark analysis was used to compare short- and long-term RFS. Univariable and multivariable analyses were used to identify prognostic factors, and subgroup analyses were performed according to high risks of recurrence. Results: A total of 85 patients underwent hepatectomy alone and 52 patients received postoperative adjuvant therapy. Compared with the hepatectomy group (HG), RFS was significantly improved in the adjuvant therapy group (ATG) (P < 0.001), but OS was not (P = 0.098). Landmark analysis revealed that RFS within 6 months of the HG was significantly different from that of the ATG (P < 0.001) but not after 6 months (P = 0.486). Multivariable analysis showed that without adjuvant therapy, high Child-Pugh classification, high alpha-fetoprotein levels, microvascular invasion, and satellite lesions were independent risk factors for recurrence within 6 months after hepatectomy. Subgroup analysis revealed that patients with MVI significantly benefited from adjuvant therapy in RFS. But for OS, adjuvant therapy was only significantly effective in patients with single tumor. The most common treatment-related adverse events during adjuvant therapy were hypertension (36.5%), rash or itching (28.8%), diarrhea (23.1%), and fatigue (21.2%). Conclusion: Postoperative adjuvant lenvatinib plus PD-1 antibody significantly improved RFS in patients with HCC at high risks of recurrence with acceptable safeties.

Neuroligin-3 activates Akt-dependent Nrf2 cascade to protect osteoblasts from oxidative stress.

Excessive oxidative stress will cause significant injury to osteoblasts, serving as one major pathological mechanism of osteoporosis. Neuroligin-3 (NLGN3) is a postsynaptic cell adhesion protein and is expressed in the bone. We here explored its potential activity against hydrogen peroxide (H2O2)-induced oxidative injury in cultured osteoblasts. In primary murine and human osteoblasts, NLGN3 stimulation dose-dependently induced Akt, Erk1/2 and S6K activation. NLGN3 pretreatment ameliorated H2O2-induced cytotoxicity and death in osteoblasts. Moreover, H2O2-induced reactive oxygen species (ROS) production and oxidative injury were alleviated with NLGN3 pretreatment in cultured osteoblasts. Further studies showed that NLGN3 activated Nrf2 signaling cascade and induced Nrf2 protein Serine-40 phosphorylation, Keap1-Nrf2 dissociation, Nrf2 protein stabilization and nuclear translocation in osteoblasts. NLGN3 also increased antioxidant response element (ARE) activity and induced expression of Nrf2-ARE-dependent genes (HO1, GCLC and NQO1) in osteoblasts. Moreover NLGN3 mitigated osteoblast oxidative injury by dexamethasone or sodium fluoride (NaF). Nrf2 cascade activation is essential for NLGN3-induced cytoprotective activity in osteoblasts. Nrf2 shRNA or knockout (KO) abolished NLGN3-induced osteoblast cytoprotection against H2O2. Contrarily forced Nrf2 cascade activation by Keap1 KO mimicked NLGN3-induced anti-oxidative activity in murine osteoblasts. Importantly, NLGN3-induced Serine-40 phosphorylation and Nrf2 cascade activation were blocked by an Akt inhibitor MK-2206 or by Akt1 shRNA. Importantly, Akt inhibition, Akt1 silencing or Nrf2 S40T mutation largely inhibited NLGN3-induced osteoblast cytoprotection against H2O2. At last, we showed that NLGN3 mRNA and protein expression was significantly downregulated in necrotic bone tissues of dexamethasone-taken patients. Taken together, NLGN3 activated Akt-dependent Nrf2 cascade to protect osteoblasts from oxidative stress.

Influence of Simulated State of Disc Degeneration and Axial Stiffness of Coupler in a Hybrid Performance Stabilisation System on the Biomechanics of a Spine Segment Model.

Spinal fusion surgery leads to the restriction of mobility in the vertebral segments postoperatively, thereby causing stress to rise at the adjacent levels, resulting in early degeneration and a high risk of adjacent vertebral fractures. Thus, to address this issue, non-fusion surgery applies some pedicle screw-based dynamic stabilisation systems to provide stability and micromotion, thereby reducing stress in the fusion segments. Among these systems, the hybrid performance stabilisation system (HPSS) combines a rigid rod, transfer screw, and coupler design to offer a semi-rigid fixation method that preserves some mobility near the fusion site and reduces the adjacent segment compensatory effects. However, further research and confirmation are needed regarding the biomechanical effects of the dynamic coupler stiffness of the HPSS on the intrinsic degenerated adjacent segment. Therefore, this study utilised the finite element method to investigate the impact of the coupler stiffness of the HPSS on the mobility of the lumbar vertebral segments and the stress distribution in the intervertebral discs under flexion, extension, and lateral bending, as well as the clinical applicability of the HPSS on the discs with intrinsic moderate and severe degeneration at the adjacent level. The analytical results indicated that, regardless of the degree of disc degeneration, the use of a dynamic coupler stiffness of 57 N/mm in the HPSS may reduce the stress concentrations at the adjacent levels. However, for severely degenerated discs, the postoperative stress on the adjacent segments with the HPSS was still higher compared with that of the discs with moderate degeneration. We conclude that, when the discs had moderate degeneration, increasing the coupler stiffness led to a decrease in disc mobility. In the case of severe disc degeneration, the effect on disc mobility by coupler stiffness was less pronounced. Increasing the coupler stiffness ked to higher stress on intervertebral discs with moderate degeneration, while its effect on stress was less pronounced for discs with severe degeneration. It is recommended that patients with severe degeneration who undergo spinal dynamic stabilisation should remain mindful of the risk of accelerated adjacent segment degeneration.

[Distribution, Source, and Ecological Risk Assessment of Persistent Organic Pollutants in Surface Sediments of Boao Coastal Waters].

Persistent organic pollutants (POPs) in the environment have the characteristics of persistence, bioaccumulation, teratogenicity, carcinogenicity, and mutagenicity. Long-term exposure of low-content POPs will also have a certain impact on marine ecosystems and human beings. The contents of three typical persistent organic pollutants[polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), and polycyclic biphenyls (PCBs)] of surface sediments were analyzed using gas chromatography and mass spectrometry (GC-MS) to assess the pollution characteristics of persistent organic pollutants in Boao coastal waters. The distribution and source of persistent organic pollutants were analyzed in this study, and the ecological risk was assessed using three different methods:the effect interval low/median method (ERL/ERM), mean effect interval median quotient method (M-ERM-Q), and mean potential impact concentration quotient method (M-PEC-Q). The results indicated that the contents (measured by dry weight) of ΣPAHs, ΣOCPs, and ΣPCBs in the study area were 4.5-367.50, 3.99-175.30, and ND-2.89 ng·g-1, respectively, which were at a low level, and the overall distribution showed a trend of gradually increasing toward the sea. The results of POPs source analysis showed that the PAHs in the study area were mainly from the combustion of wood and coal. Among OCPs, the HCH was mainly from lindane, the historical land-based input had been completely degraded, and the DDT was mainly the traditional DDTs pesticides, with additional continuous DDT input. The PCBs were primarily pentachlorobiphenyls, which might have come from the release of paint on the bottom of the hull in the early stage of shipping and the peeling off of paint from old ships. The ecological risk assessment results showed that there was little difference among the assessment results of the three methods, which showed that only phenanthrene monomer of PAHs in the study area had a slight negative impact, and the DDT and the γ-HCH among PAHs would cause great ecological risk, whereas PCBs and other pollutants would not cause ecological risk. On the whole, the possibility of comprehensive ecological risk caused by the three pollutants was very small.