Strengthening and Embrittling Mechanism of Super 304H Steel during Long-Term Aging at 650 °C.

Super 304H has been a crucial material for ultra-supercritical boilers. However, the relationship between microstructure evolution, strengthening mechanism, and embrittling behavior during long-term aging was lacking investigation. This investigation aimed to reveal the strengthening and embrittling mechanism from precipitates in Super 304H. The results showed that the hardness increment came from the grain boundary's M23C6 (GB's M23C6) and intragranular nano Cu-rich particles. After being aged for 5000 h, the GB's M23C6 and nano Cu-rich particles provided a hardness increment of approximately 10 HV and 30 HV, respectively. The impact toughness gradually decreased from 213 J/cm2 to 161 J/cm2 with the extending aging time. For the aged Super 304H, the GB's M23C6 provided a higher cracking source. In addition, the nano Cu-rich particle restricted the twin-induced plastic deformation of austenitic grain and depressed the absorbed energy from austenitic grain deformation.

Nerve Guide Conduits Integrated with Fisetin-Loaded Chitosan Hydrogels for Reducing Oxidative Stress, Inflammation, and Nerve Regeneration.

Peripheral nerve injuries (PNI) represent a prevalent and severe category of damage resulting from traumatic incidents. Predominantly, the deficiency in nerve regeneration can be ascribed to enduring inflammatory reactions, hence imposing substantial clinical implications for patients. Fisetin, a flavonoid derived from plants, is naturally present in an array of vegetables and fruits, including strawberries, apples, onions, and cucumbers. It exhibits immunomodulatory properties through the reduction of inflammation and oxidative stress. In the present research, a nerve defect is addressed for the first time utilizing a scaffold primed for controlled fisetin release. In this regard, fisetin-loaded chitosan hydrogels are incorporated into the lumen of polycaprolactone (PCL) nerve guide conduits (NGCs). The hydrogel maintained a steady release of an appropriate fisetin dosage. The study outcomes indicated that the fisetin/chitosan/polycaprolactone (FIS/CS/PCL) NGCs amplified Schwann cell proliferation and neural expression, curtailed oxidative stress, alleviated inflammation, and improved functions, electrophysiological properties, and morphology. This pioneering scaffold has the potential to contribute significantly to the field of neuroengineering.

Chlorogenic acid releasing microspheres enhanced electrospun conduits to promote peripheral nerve regeneration.

Chlorogenic acid (CGA) has been confirmed as a polyphenol, and existing research has suggested the high bioactivity of CGA for therapeutic effects on a wide variety of diseases. Despite the existing reports of anti-inflammatory, antioxidant, and neuroprotective effects of CGA, the role and mechanism of CGA in facilitating the regeneration of peripheral nerve defects have been rarely investigated. Herein, a biodegradable polycaprolactone (PCL) conduit with embedded CGA-releasing GelMA microspheres (CGM/PCL) was successfully prepared and used for repairing a rate model with sciatic nerve defects. CGM and CGM/PCL conduits displayed high in vitro biocompatibility and can support the growth of cells for nerve regeneration. Furthermore, CGM/PCL conduits displayed high performance which is close to that of autologous nerve grafts in promoting in vivo PNI regeneration, compared with PCL conduits. The sciatic nerve functional index analysis, electrophysiological examination, and immunological analysis performed to evaluate the functional recovery of the injurious sciatic nerve of rats have indeed proved the favorable effects of CGM/PCL conduits. The result of this study not only aimed to explore CGA's contribution to nerve regeneration but also provided a new strategy for designing and preparing functional NGCs for PNI treatment.

Pathophysiological consequences and treatment strategy of obstructive jaundice.

Obstructive jaundice (OJ) is a common problem in daily clinical practice. However, completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management. The effects of OJ are widespread, affecting the biliary tree, hepatic cells, liver function, and causing systemic complications. The lack of bile in the intestine, destruction of the intestinal mucosal barrier, and increased absorption of endotoxins can lead to endotoxemia, production of proinflammatory cytokines, and induce systemic inflammatory response syndrome, ultimately leading to multiple organ dysfunction syndrome. Proper management of OJ includes adequate water supply and electrolyte replacement, nutritional support, preventive antibiotics, pain relief, and itching relief. The surgical treatment of OJ depends on the cause, location, and severity of the obstruction. Biliary drainage, surgery, and endoscopic intervention are potential treatment options depending on the patient's condition. In addition to modern medical treatments, Traditional Chinese medicine may offer therapeutic benefits for OJ. A comprehensive search was conducted on PubMed for relevant articles published up to August 1970. This review discusses in detail the pathophysiological changes associated with OJ and presents effective strategies for managing the condition.

Exosomes derived from schwann cells alleviate mitochondrial dysfunction and necroptosis after spinal cord injury via AMPK signaling pathway-mediated mitophagy.

Although spinal cord injury (SCI) represents a primary etiology of disability, currently, there are exist limited viable therapies modalities. Acquiring comprehension of the diverse pathways that drive mitochondrial aberration may facilitate the identification of noteworthy targets for ameliorating the deleterious consequences precipitated by SCI. Our objective was to determine the efficiency of exosomes produced from Schwann cells (SCDEs) in protecting against mitochondrial dysfunction. This evaluation was conducted using a rat model of compressed SCI and in vitro experiments involving rat pheochromocytoma cells (PC12) exposed to oxygen-glucose deprivation (OGD). The conducted experiments yielded evidence that SCDEs effectively mitigated oxidative stress (OS) and inflammation subsequent to SCI, while concurrently diminishing necroptosis. Subsequent in vitro inquiry assessed the impact of SCDEs on PC12, with a specific emphasis on mitochondrial functionality, necrotic cell prevalence, and mitophagy. The study findings revealed that SCDEs enhanced mitophagy in PC12 cells, leading to a decrease in the generation of reactive oxygen species (ROS) and inflammatory cytokines (CK) provoked by OGD-induced injury. This, in turn, mitigated mitochondrial dysfunction and necroptosis. Mechanistically, SCDEs facilitated cellular mitophagy through activation of the AMPK signaling pathway. In conclusion, our data strongly support the notion that SCDEs hold considerable promise as a therapeutic approach for managing SCI. Furthermore, our investigation serves to elucidate the pivotal role of AMPK-mediated mitophagy in reducing cell damage, thereby unveiling novel prospects for enhancing neuro-pathological outcomes following SCI.

Inhibition of autophagy and RIP1/RIP3/MLKL-mediated necroptosis by edaravone attenuates blood spinal cord barrier disruption following spinal cord injury.

The disruption of the blood spinal cord barrier (BSCB) after spinal cord injury (SCI) can trigger secondary tissue damage. Edaravone is likely to protect the BSCB as a free radical scavenger, whereas it has been rarely reported thus far. In this study, the protective effect of edaravone was investigated with the use of compression spinal cord injured rats and human brain microvascular endothelial cells (HBMECs) injury. As indicated by the result of this study, edaravone treatment facilitated functional recovery after rats were subjected to SCI, ameliorated the vascular damage, and up-regulated the expression of BSCB-associated proteins. In vitro results, edaravone improved HBMECs viability, restored intercellular junctions, and promoted cellular angiogenic activities. It is noteworthy that autophagy was activated and RIP1/RIP3/MLKL phosphorylation was notably up-regulated. However, edaravone treatment exhibited the capability of mitigating above-mentioned tendency in vivo and in vitro. Moreover, rapamycin (Rapa) treatment deteriorated the protective effect of edaravone while aggravating the phosphorylation of RIP1/RIP3/MLKL expression. In the model of necrotic activator-induced HBMECs, autophagic expression was increased, whereas edaravone prevented autophagy and phosphorylation of RIP1/RIP3/MLKL. In general, our results suggested that edaravone is capable of reducing the destruction of BSCB and promoting functional recovery after SCI. The possible underlying mechanism is that edaravone is capable of protecting angiogenic activity and improving autophagy and the phosphorylation of RIP1/RIP3/MLKL, as well as their mutual deterioration. Accordingly, edaravone can be a favorable option for the treatment of SCI.

A novel hybrid algorithm based on Harris Hawks for tumor feature gene selection.

Background: Gene expression data are often used to classify cancer genes. In such high-dimensional datasets, however, only a few feature genes are closely related to tumors. Therefore, it is important to accurately select a subset of feature genes with high contributions to cancer classification. Methods: In this article, a new three-stage hybrid gene selection method is proposed that combines a variance filter, extremely randomized tree and Harris Hawks (VEH). In the first stage, we evaluated each gene in the dataset through the variance filter and selected the feature genes that meet the variance threshold. In the second stage, we use extremely randomized tree to further eliminate irrelevant genes. Finally, we used the Harris Hawks algorithm to select the gene subset from the previous two stages to obtain the optimal feature gene subset. Results: We evaluated the proposed method using three different classifiers on eight published microarray gene expression datasets. The results showed a 100% classification accuracy for VEH in gastric cancer, acute lymphoblastic leukemia and ovarian cancer, and an average classification accuracy of 95.33% across a variety of other cancers. Compared with other advanced feature selection algorithms, VEH has obvious advantages when measured by many evaluation criteria.

A new hybrid algorithm for three-stage gene selection based on whale optimization.

In biomedical data mining, the gene dimension is often much larger than the sample size. To solve this problem, we need to use a feature selection algorithm to select feature gene subsets with a strong correlation with phenotype to ensure the accuracy of subsequent analysis. This paper presents a new three-stage hybrid feature gene selection method, that combines a variance filter, extremely randomized tree, and whale optimization algorithm. First, a variance filter is used to reduce the dimension of the feature gene space, and an extremely randomized tree is used to further reduce the feature gene set. Finally, the whale optimization algorithm is used to select the optimal feature gene subset. We evaluate the proposed method with three different classifiers in seven published gene expression profile datasets and compare it with other advanced feature selection algorithms. The results show that the proposed method has significant advantages in a variety of evaluation indicators.

PCL NGCs integrated with urolithin-A-loaded hydrogels for nerve regeneration.

Inflammation and oxidative stress are among the leading causes of poor prognosis after peripheral nerve injury (PNI). Urolithin-A (UA), an intermediate product produced by the catabolism of ellagitannins in the gastrointestinal tract, has anti-inflammatory, antioxidant, and immunomodulatory properties for inflammation, oxidative damage, and aging-related diseases. Hence, we prepared UA-loaded hydrogels and embedded them in the lumen of PCL nerve guide conduits (NGCs). The hydrogels continuously released appropriate doses of UA into the microenvironment. Based on in vitro studies, UA facilitates cell proliferation and reduces oxidative damage. Besides, the experimental evaluation revealed good biocompatibility of the materials involved. We implanted NGCs into rat models to bridge the sciatic nerve defects in an in vivo study. The sciatic functional index of the PCL/collagen/UA group was comparable to that of the autograft group. Additionally, the consequences of electrophysiological, gastrocnemius muscle and nerve histology assessment of the PCL/collagen/UA group were better than those in the PCL and PCL/collagen groups and close to those in the autograft group. In this study, UA sustained release via the PCL/collagen/UA NGC was found to be an effective alternative treatment for PNI, validating our hypothesis that UA could promote regeneration of nerve tissue.

Correction: PCL NGCs integrated with urolithin-A-loaded hydrogels for nerve regeneration.

Correction for 'PCL NGCs integrated with urolithin-A-loaded hydrogels for nerve regeneration' by Xue-Han Jin et al., J. Mater. Chem. B, 2022, https://doi.org/10.1039/D2TB01624A.

Identification and validation of the necroptosis-related gene signature related to prognosis and tumor immune in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer, which is characterized by complicated etiology, excessive heterogeneity, and poor prognosis. Necroptosis is a new kind of programmed cell death, which is intently associated with the occurrence and development of tumors. Although researchers have had a deep understanding of necroptosis in recent years, the expression level of necroptosis-related genes in HCC and its relationship with the survival time of HCC patients are not clear. METHODS: According to the expression of necroptosis-related genes and the survival of HCC patients, HCC patients in the TCGA database were divided into 2 groups that were relatively independent of each other. The genes related to the survival time of HCC patients were screened from the 2 groups of differentially expressed genes. By using the Least Absolute Shrinkage and Selection Operator Cox regression analysis, the optimal λ value was obtained, and the 10-gene signature model was established. RESULTS: According to the median risk score of the TCGA cohort, HCC patients were averagely divided into high- and low-risk groups. Compared with the low-risk group, the death toll of the high-risk group was relatively higher and the survival time was relatively shorter. Principal component analysis and t-distributed stochastic neighbor embedding analysis showed that there was a significant separation between high- and low-risk groups. Through Kaplan-Meier analysis, it was found that the survival time of HCC patients in the high-risk group was significantly shorter than that in the low-risk group. Through receiver operating characteristic analysis, it was found that the sensitivity and specificity of the model were good. We also make a comprehensive analysis of the international cancer genome consortium database as a verification queue and prove the reliability of the 10-gene signature model. Gene Ontolog, Kyoto Encyclopedia of Genes and Genomes, and single-sample gene set enrichment analysis showed that many biological processes and pathways related to immunity had been enriched, and the antitumor immune function was weakened in the high-risk population. CONCLUSION: The risk score can be considered as an independent prognostic factor to predict the prognosis of patients with HCC, and necroptosis-related genes are also closely related to tumor immune function.

The mechanism of Yinchenhao decoction in treating obstructive-jaundice-induced liver injury based on Nrf2 signaling pathway.

BACKGROUND: Obstructive jaundice (OJ) is caused by bile excretion disorder after partial or complete bile duct obstruction. It may cause liver injury through various mechanisms. Traditional Chinese medicine (TCM) has a lot of advantages in treating OJ. The recovery of liver function can be accelerated by combining Chinese medicine treatment with existing clinical practice. Yinchenhao decoction (YCHD), a TCM formula, has been used to treat jaundice. Although much progress has been made in recent years in understanding the mechanism of YCHD in treating OJ-induced liver injury, it is still not clear. AIM: To investigate chemical components of YCHD that are effective in the treatment of OJ and predict the mechanism of YCHD. METHODS: The active components and putative targets of YCHD were predicted using a network pharmacology approach. Gene Ontology biological process and Kyoto Encyclopedia of Genes and Genomes path enrichment analysis were carried out by cluster profile. We predicted the biological processes, possible targets, and associated signaling pathways that YCHD may involve in the treatment of OJ. Thirty male Sprague-Dawley rats were randomly divided into three groups, each consisting of 10 rats: the sham group (Group S), the OJ model group (Group M), and the YCHD-treated group (Group Y). The sham group only received laparotomy. The OJ model was established by ligating the common bile duct twice in Groups M and Y. For 1 wk, rats in Group Y were given a gavage of YCHD (3.6 mL/kg) twice daily, whereas rats in Groups S and M were given the same amount of physiological saline after intragastric administration daily. After 7 d, all rats were killed, and the liver and blood samples were collected for histopathological and biochemical examinations. Total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), and aspartate transaminase (AST) levels in the blood samples were detected. The gene expression levels of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), and the nucleus positive rate of NF-E2 related factor 2 (Nrf2) protein were measured. Western blot analyses were used to detect the protein and gene expression levels of Nrf2, Kelch-like ECH-associated protein 1, NAD(P)H quinone dehydrogenase 1 (NQO1), and glutathione-S-transferase (GST) in the liver tissues. One-way analysis of variance was used to evaluate the statistical differences using the statistical package for the social sciences 23.0 software. Intergroup comparisons were followed by the least significant difference test and Dunnett's test. RESULTS: The effects of YCHD on OJ involve biological processes such as DNA transcription factor binding, RNA polymerase II specific regulation, DNA binding transcriptional activator activity, and nuclear receptor activity. The protective effects of YCHD against OJ were closely related to 20 pathways, including the hepatitis-B, the mitogen-activated protein kinase, the phosphatidylinositol 3-kinase/protein kinase B, and tumor necrosis factor signaling pathways. YCHD alleviated the swelling and necrosis of hepatocytes. Following YCHD treatment, the serum levels of TBIL (176.39 ± 17.03 µmol/L vs 132.23 ± 13.88 µmol/L, P < 0.01), DBIL (141.41 ± 14.66 µmol/L vs 106.43 ± 10.88 µmol/L, P < 0.01), ALT (332.07 ± 34.34 U/L vs 269.97 ± 24.78 U/L, P < 0.05), and AST (411.44 ± 47.64 U/L vs 305.47 ± 29.36 U/L, P < 0.01) decreased. YCHD promoted the translocation of Nrf2 into the nucleus (12.78 ± 0.99 % vs 60.77 ± 1.90 %, P < 0.001). After YCHD treatment, we found a decrease in iNOS (0.30 ± 0.02 vs 0.20 ± 0.02, P < 0.001) and an increase in eNOS (0.18 ± 0.02 vs 0.32 ± 0.02, P < 0.001). Meanwhile, in OJ rats, YCHD increased the expressions of Nrf2 (0.57 ± 0.03 vs 1.18 ± 0.10, P < 0.001), NQO1 (0.13 ± 0.09 vs 1.19 ± 0.07, P < 0.001), and GST (0.12 ± 0.02 vs 0.50 ± 0.05, P < 0.001), implying that the potential mechanism of YCHD against OJ-induced liver injury was the upregulation of the Nrf2 signaling pathway. CONCLUSION: OJ-induced liver injury is associated with the Nrf2 signaling pathway. YCHD can reduce liver injury and oxidative damage by upregulating the Nrf2 pathway.

Effectiveness and safety of a less-invasive MCL reconstruction technique for contracted or ossified ligaments in patients with elbow stiffness: An open-label, non-randomised, prospective, multicentre trial in China.

Background: The elbow joint is sensitive to trauma from accidents, sports injuries, and surgical trauma. Some patients develop ossification or contracture of the medial collateral ligament (MCL) after elbow trauma. A less invasive reconstruction of the MCL can be performed after resection of diseased MCL. The biomechanical characteristics of this technique have been demonstrated and validated. However, its clinical effectiveness and safety require further confirmation in clinical practice. Methods: This open-label, non-randomised, prospective, multicentre trial included consecutive patients with elbow stiffness from five orthopaedic centres in China. Patients willing to participate in the study, with elbow stiffness caused by traumatic injury, who had reached skeletal maturity, and who had a range of motion of <100° were eligible for inclusion. Patients with immunological or metabolic causes of elbow stiffness, burns, or central nervous system injuries were excluded. In addition, patients who did not require MCL release and reconstruction after intraoperative release of other structures were also excluded. All patients underwent resection of the diseased MCL part in an open arthrolysis. Medial stability of the elbow was reconstructed using a less invasive MCL reconstruction technique that uses fascia and tendon patches. In this study, the primary outcomes, including stability, Mayo Elbow Performance Score (MEPS), Amadio score, were used to comprehensively evaluate this technique. Outcomes were assessed at 6 weeks, 6 months, and 1 year postoperatively and annually thereafter. This study reports the results of one arm of the trial that has been registered with the Chinese Clinical Trial Registry (chictr.org.cn), ChiCTR-INC-16010019. Findings: Between January 1, 2017 and March 1, 2020, 104 eligible patients were enrolled. The mean follow-up time was 43·47 (95% CI, 41·45 - 45·49) months. Among all 104 patients, 100 (96%) patients who underwent MCL reconstruction retained medial stability at the last follow-up. All outcomes from the last follow-up were used for comparison with the preoperative outcomes. No differences in preoperative and postoperative stability scores were observed (P = 0·7820). Extension, flexion, pronation, and supination of the injured elbow improved significantly (P < 0·0001, P < 0·0001, P < 0·0001, P < 0·0001). The mean range of motion (ROM) and forearm rotational range of motion (FRR) increased by 71·25° (152%) (P < 0·0001) and 30·83° (25%) (P < 0·0001), respectively. Additionally, the Mayo Elbow Performance Score (MEPS) and muscle strength had increased after evaluation at follow-ups (P < 0·0001, P < 0·0001). Drastic pain relief and nerve symptom reduction were observed, as evaluated using VAS scores and Amadio scores, respectively (P < 0·0001, P < 0·0001). Seventeen (16%) patients experienced a recurrence of elbow stiffness of varying severity, but only two patients had poor or fair results. Several common and non-severe complications, including infection in one (1%) patient, new nerve symptoms in seven (7%) patients, new pain in one (1%) patient, fracture in one (1%) patient, and valgus instability in four (4%) patients, were observed and properly treated in this study. Interpretation: The less invasive MCL reconstruction technique using fascia and tendon patches is an effective method for restoring medial stability in patients with elbow stiffness after complete arthrolysis with certain safety. The technique shows prospects for elbow MCL reconstruction in clinical practice. Funding: The study was supported by the National Key Research and Development Program of China (No. 2021YFC2400805), National Natural Science Foundation of China (No. 81830076), Young Elite Scientist Sponsorship Program by Cast (No. YESS20200153), Shanghai Sailing Program (No. 20YF1436000), Shanghai Municipal Science and Technology Commission Foundation (No.19ZR1439200), Municipal Hospital Newly-developing Cutting-edge Technologies Joint Research Program of Shanghai Shenkang Hospital Development Centre (No. SHDC12018130).

Mineralized Enzyme-Based Biomaterials with Superior Bioactivities for Bone Regeneration.

The formation and metabolic balance of bone tissue is a controllable process of biomineralization, which is regulated by various cells, biomolecules, and ions. Enzyme molecules play an important role in this process, and alkaline phosphatase (ALP) is one of the most critical factors. In this study, inspired by the process of bone biomineralization, a biomimetic strategy is achieved for the preparation of mineralized ALP nanoparticles (MALPNs), by taking advantages of the unique reaction between ALP and calcium ions in Dulbecco's modified Eagle's medium. Benefiting from the mild biomineralization reaction, the MALPN system highly maintains the activity of ALP. Furthermore, the in vitro studies show that the MALPN system significantly enhances the proliferation of bone marrow mesenchymal stem cells and upregulates their osteogenic differentiation. When evaluated as synthetic graft materials for bone regeneration, the MALPN-incorporated gelatin methacryloyl graft shows excellent mechanical properties, a sustained release profile of ALP, and high biocompatibility and efficacy in guiding bone regeneration and vascularization for critical-sized rat calvarial defect. Moreover, we also demonstrate that the biomimetic mineralization strategy can be adopted for other proteins such as acid phosphatase, bovine serum albumin, fibrinogen, and gelatin, suggesting its universality for constructing mineralized protein-/enzyme-based bioactive materials for the application of tissue regeneration.

Advances in prognostic and therapeutic targets for hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The hippo signaling pathway.

Primary liver cancer is the sixth most frequently diagnosed cancer worldwide and the third leading cause of cancer-related death. The majority of the primary liver cancer cases are hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Worldwide, there is an increasing incidence of primary liver cancer cases due to multiple risk factors ranging from parasites and viruses to metabolic diseases and lifestyles. Often, patients are diagnosed at advanced stages, depriving them of surgical curability benefits. Moreover, the efficacy of the available chemotherapeutics is limited in advanced stages. Furthermore, tumor metastases and recurrence make primary liver cancer management exceptionally challenging. Thus, exploring the molecular mechanisms for the development and progression of primary liver cancer is critical in improving diagnostic, treatment, prognostication, and surveillance modalities. These mechanisms facilitate the discovery of specific targets that are critical for novel and more efficient treatments. Consequently, the Hippo signaling pathway executing a pivotal role in organogenesis, hemostasis, and regeneration of tissues, regulates liver cells proliferation, and apoptosis. Cell polarity or adhesion molecules and cellular metabolic status are some of the biological activators of the pathway. Thus, understanding the mechanisms exhibited by the Hippo pathway is critical to the development of novel targeted therapies. This study reviews the advances in identifying therapeutic targets and prognostic markers of the Hippo pathway for primary liver cancer in the past six years.

Identification of the ferroptosis-related ceRNA network related to prognosis and tumor immunity for gastric cancer.

Gastric cancer (GC) is a highly invasive course and has a very poor prognosis. Because there are no obvious symptoms in the early stage, most patients with GC are diagnosed in the late stage. The effective diagnosis, prognosis biomarkers and treatment targets of GC can solve this problem to a great extent. Although researchers have done a lot of research on GC in recent years, the relationship between the competing endogenous RNA (ceRNA) network of ferroptosis-related genes and the GC remains to be explored. Therefore, the research done in this paper has become particularly important. Download the expression data and clinical survival data about stomach adenocarcinoma from UCSC Xena and The Cancer Genome Atlas (TCGA) platform. Using bioinformatics tools to screen lncRNAs, miRNAs and mRNAs that are differentially expressed in GC samples and normal samples and related to the prognosis of GC. Then, screening lncRNAs, miRNAs and mRNAs with targeted relationships from the Starbase database. Subsequently, correlation analysis and survival analysis were carried out respectively. Finally, we get a ceRNA network related to the prognosis of GC patients. Cell experiments confirmed the results obtained by bioinformatics. This is critical for the discovery of the diagnosis, prognosis biomarkers and treatment targets.

Targeting C3b/C4b and VEGF with a bispecific fusion protein optimized for neovascular age-related macular degeneration therapy.

Antiangiogenesis therapies targeting vascular endothelial growth factor (VEGF) have revolutionized the treatment of neovascular ocular diseases, including neovascular age-related macular degeneration (nAMD). Compelling evidence has implicated the vital role of complement system dysregulation in AMD pathogenesis, implying it as a potential therapeutic strategy for geographic atrophy in dry AMD and to enhance the efficacy of anti-VEGF monotherapies in nAMD. This study reports the preclinical assessment and phase 1 clinical outcomes of a bispecific fusion protein, efdamrofusp alfa (code: IBI302), which is capable of neutralizing both VEGF isoforms and C3b/C4b. Efdamrofusp alfa showed superior efficacy over anti-VEGF monotherapy in a mouse laser-induced choroidal neovascularization (CNV) model after intravitreal delivery. Dual inhibition of VEGF and the complement activation was found to further inhibit macrophage infiltration and M2 macrophage polarization. Intravitreal efdamrofusp alfa demonstrated favorable safety profiles and exhibited antiangiogenetic efficacy in a nonhuman primate laser-induced CNV model. A phase 1 dose-escalating clinical trial (NCT03814291) was thus conducted on the basis of the preclinical data. Preliminary results showed that efdamrofusp alfa was well tolerated in patients with nAMD. These data suggest that efdamrofusp alfa might be effective for treating nAMD and possibly other complement-related ocular conditions.

Development and validation of a prognostic nomogram for open elbow arthrolysis : the Shanghai Prediction model for Elbow Stiffness Surgical Outcome.

AIMS: The aim of this study was to develop and internally validate a prognostic nomogram to predict the probability of gaining a functional range of motion (ROM ≥ 120°) after open arthrolysis of the elbow in patients with post-traumatic stiffness of the elbow. METHODS: We developed the Shanghai Prediction Model for Elbow Stiffness Surgical Outcome (SPESSO) based on a dataset of 551 patients who underwent open arthrolysis of the elbow in four institutions. Demographic and clinical characteristics were collected from medical records. The least absolute shrinkage and selection operator regression model was used to optimize the selection of relevant features. Multivariable logistic regression analysis was used to build the SPESSO. Its prediction performance was evaluated using the concordance index (C-index) and a calibration graph. Internal validation was conducted using bootstrapping validation. RESULTS: BMI, the duration of stiffness, the preoperative ROM, the preoperative intensity of pain, and grade of post-traumatic osteoarthritis of the elbow were identified as predictors of outcome and incorporated to construct the nomogram. SPESSO displayed good discrimination with a C-index of 0.73 (95% confidence interval 0.64 to 0.81). A high C-index value of 0.70 could still be reached in the interval validation. The calibration graph showed good agreement between the nomogram prediction and the outcome. CONCLUSION: The newly developed SPESSO is a valid and convenient model which can be used to predict the outcome of open arthrolysis of the elbow. It could assist clinicians in counselling patients regarding the choice and expectations of treatment. Cite this article: Bone Joint J 2022;104-B(4):486-494.

Ti3C2Tx MXene-Coated Electrospun PCL Conduits for Enhancing Neurite Regeneration and Angiogenesis.

An electrical signal is the key basis of normal physiological function of the nerve, and the stimulation of the electric signal also plays a very special role in the repair process of nerve injury. Electric stimulation is shown to be effective in promoting axonal regeneration and myelination, thereby promoting nerve injury repair. At present, it is considered that electric conduction recovery is a key aspect of regeneration and repair of long nerve defects. Conductive neural scaffolds have attracted more and more attention due to their similar electrical properties and good biocompatibility with normal nerves. Herein, PCL and MXene-PCL nerve guidance conduits (NGCs) were prepared; their effect on nerve regeneration was evaluated in vitro and in vivo. The results show that the NGCs have good biocompatibility in vitro. Furthermore, a sciatic nerve defect model (15 mm) of SD rats was made, and then the fabricated NGCs were implanted. MXene-PCL NGCs show similar results with the autograft in the sciatic function index, electrophysiological examination, angiogenesis, and morphological nerve regeneration. It is possible that the conductive MXene-PCL NGC could transmit physiological neural electric signals, induce angiogenesis, and stimulate nerve regeneration. This paper presents a novel design of MXene-PCL NGC that could transmit self-originated electric stimulation. In the future, it can be combined with other features to promote nerve regeneration.

Anatomy and assessment of a modified technique during totally robotic distal gastrectomy: A retrospective cohort study.

Background: Robotic surgery has potential benefits in the management of gastric cancer patients. This study compares the outcomes between totally robotic distal gastrectomy (TRDG) with modified port placement and arm positioning technique and conventional totally laparoscopic distal gastrectomy (CTLDG). Materials and methods: Fifty-two patients were enrolled into the study following a retrospective review of an in-patient database between January 2019 and June 2021. Patients who underwent gastric resection with the modified robotic technique were recruited into the study. Patients who did not receive treatment using the modified technique were excluded from the study. Data on demographic, clinical data and surgical outcomes were collected, analyzed, and presented. All statistical analyses were done using IBM SPSS statistical software. Results: Nineteen patients were in the TRDG group, and their mean age was 60.42 ± 11.53 years. There were no differences in demographic characteristics (all p > 0.05); nonetheless, laparoscopic patients had a significantly higher preoperative albumin level (p = 0.000). The operative time was longer in the TRDG group (223min), but the difference was insignificant. The reconstruction time was significantly shorter for the laparoscopic group (p = 0.000). Except for a significantly higher value of postoperative albumin level (p-value = 0.005) in the robotic group, there were no significant differences in all other surgical outcomes between the two groups. One (5.3%) patient had a severe complication in the robotic group compared to four (12.1%) in the laparoscopic group. Nevertheless, the differences in complications were statistically insignificant. Conclusion: The modified approach is a safe and feasible in totally robotic distal gastrectomy for the treatment of gastric cancer patients.