Preoperative prediction of perineural invasion of rectal cancer based on a magnetic resonance imaging radiomics model: A dual-center study.

BACKGROUND: Perineural invasion (PNI) has been used as an important pathological indicator and independent prognostic factor for patients with rectal cancer (RC). Preoperative prediction of PNI status is helpful for individualized treatment of RC. Recently, several radiomics studies have been used to predict the PNI status in RC, demonstrating a good predictive effect, but the results lacked generalizability. The preoperative prediction of PNI status is still challenging and needs further study. AIM: To establish and validate an optimal radiomics model for predicting PNI status preoperatively in RC patients. METHODS: This retrospective study enrolled 244 postoperative patients with pathologically confirmed RC from two independent centers. The patients underwent pre-operative high-resolution magnetic resonance imaging (MRI) between May 2019 and August 2022. Quantitative radiomics features were extracted and selected from oblique axial T2-weighted imaging (T2WI) and contrast-enhanced T1WI (T1CE) sequences. The radiomics signatures were constructed using logistic regression analysis and the predictive potential of various sequences was compared (T2WI, T1CE and T2WI + T1CE fusion sequences). A clinical-radiomics (CR) model was established by combining the radiomics features and clinical risk factors. The internal and external validation groups were used to validate the proposed models. The area under the receiver operating characteristic curve (AUC), DeLong test, net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curve, and decision curve analysis (DCA) were used to evaluate the model performance. RESULTS: Among the radiomics models, the T2WI + T1CE fusion sequences model showed the best predictive performance, in the training and internal validation groups, the AUCs of the fusion sequence model were 0.839 [95% confidence interval (CI): 0.757-0.921] and 0.787 (95%CI: 0.650-0.923), which were higher than those of the T2WI and T1CE sequence models. The CR model constructed by combining clinical risk factors had the best predictive performance. In the training and internal and external validation groups, the AUCs of the CR model were 0.889 (95%CI: 0.824-0.954), 0.889 (95%CI: 0.803-0.976) and 0.894 (95%CI: 0.814-0.974). Delong test, NRI, and IDI showed that the CR model had significant differences from other models (P < 0.05). Calibration curves demonstrated good agreement, and DCA revealed significant benefits of the CR model. CONCLUSION: The CR model based on preoperative MRI radiomics features and clinical risk factors can preoperatively predict the PNI status of RC noninvasively, which facilitates individualized treatment of RC patients.

Genetically redirected HBV-specific T cells target HBsAg-positive hepatocytes and primary lesions in HBV-associated HCC.

Background and Aims: HBV-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it in an HBV-related HCC patient (NCT05339321). Methods: GMP-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh:A, BCLC:B, ECOG:0, HBeAg-, serum HBsAg+, hepatocytes 10% HBsAg+) received 7.9x107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated. Results: SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-hepatoma cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1404 U/ml, and concurrently, serum HBsAg started decreasing by 3.84log and remained <1 IU/ml for over six months. HBsAg expressing hepatocytes in liver biopsies were undetectable after73 days. The patient achieved a partial response according to mRECIST score with a >70% reduction of target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient's blood. Conclusions: SCG101 T-cell therapy showed encouraging efficacy and safety in pre-clinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.

Catalytic Pyrolysis of Polypropylene for Cable Semiconductive Buffer Layers.

With the progress of the power grid system, the coverage area of cables is widening, and the problem of cable faults is gradually coming to affect people's daily lives. While the vast majority of cable faults are caused by the ablation of the cable buffer layer, polypropylene (PP), as a common cable buffer material, has pyrolysis properties that critically impact cable faults. Studying the semiconductive buffer layer of polypropylene (PP) and its pyrolysis properties allows us to obtain a clearer picture of the pyrolysis products formed during PP ablation. This understanding aids in the accurate diagnosis of cable faults and the identification of ablation events. In this study, the effects of temperature and catalyst (H-Zeolite Standard Oil Corporation Of New York (Socony) Mobil-Five (HZSM-5)) content on the PP thermolysis product distribution were studied by using an online tubular pyrolysis furnace-mass spectrometry (MS) experimental platform. The results showed that PP/40% HZSM-5 presented the highest thermolytic efficiency and relative yield of the main products at 400 °C.

Preliminary investigation on the causes of red tides in Qinhuangdao coastal areas in 2022.

To explore the causes of red tides in Qinhuangdao coastal water, we conducted surveys on both water quality and red tides during April to September of 2022 and analyzed the relationships between main environmental factors and red tide organisms through the factor analysis and canonical correspondence analysis. The results showed that there were eight red tides along the coast of Qinhuangdao in 2022, with a cumulative blooming area of 716.1 km2. The red tides could be divided into three kinds based on the major blooming organisms and occurrence time, Noctiluca scintillans bloom, diatom-euglena (Skeletonema costatum, Eutreptiella gymnastica, Pseudo-nitzschia spp.) bloom, and dinoflagellate (Scrippsiella trochoidea and Ceratium furca) bloom. Seasonal factor played roles mainly during July to September, while inorganic nutrients including nitrogen and phosphorus influenced the blooms mainly in April and July. The canonical correspondence analysis suggested that N. scintillans preferred low temperature, and often bloomed with high concentrations of ammonium nitrogen and dissolved inorganic phosphorus. S. costatum, E. gymnastica, and Pseudo-nitzschia spp. could tolerate broad ranges of various environmental factors, but favored high temperature and nitrogen-rich seawater. C. furca and S. trochoidea had higher survival rate and competitiveness in phosphate-poor waters. Combined the results from both analyses, we concluded that the causes for the three kinds of red tide processes in Qinhuangdao coastal areas in 2022 were different. Adequate diet algae and appropriate water temperature were important factors triggering and maintaining the N. scintillans bloom. Suitable temperature, salinity and eutrophication were the main reasons for the diatom-euglena bloom. The abundant nutrients and seawater disturbance promoted the germination of S. trochoidea cysts, while phosphorus limitation caused the blooming organism switched to C. furca and maintained the bloom hereafter.

Giant cell tumor of bone at distal radius suffered more soft tissue recurrence and ultrasonography is effective to detect the soft tissue recurrence.

BACKGROUND: Soft tissue recurrence of giant cell tumor of bone (GCTB) is rare. This study aims to provide its prevalence, recurrent locations, risk factors, effective detection methods and a modified classification for this recurrence. METHODS: Patients with soft tissue recurrence after primary surgery for GCTB were screened from January 2003 to December 2022. General data, recurrence frequency, types according to an original classification (type-I: peripheral ossification; type-II: central ossification; type-III: without ossification), a modified classification with more detailed subtypes (type I-1: ≤ 1/2 peripheral ossification; type I-2: ≥ 1/2 peripheral ossification; type II-1: ≤ 1/2 central ossification; type II-2: ≥ 1/2 central ossification; type III: without ossification), locations, detection methods such as ultrasonography, X-ray, CT or MRI, Musculoskeletal Tumor Society (MSTS) scores were recorded. Multivariate regression analysis was conducted to identify risk factors for recurrence frequency. RESULTS: A total of 558 recurrent cases were identified from 2009 patients with GCTB. Among them, 32 were soft tissue recurrence. The total recurrence rate was 27.78% (558/2009). Soft tissue recurrence rate was 5.73% among 558 recurrent cases, and 1.59% among 2009 GCTB patients, respectively. After excluding one patient lost to follow-up, 10 males and 21 females with the mean age of 28.52 ± 9.93 (16-57) years were included. The definitive diagnosis of all recurrences was confirmed by postoperative pathology. The interval from primary surgery to the first recurrence was 23.23 ± 26.12 (2-27) months. Eight recurrences occurred from primary GCTB located at distal radius, followed by distal femur (6 cases). Recurrence occurred twice in 12 patients and 3 times in 7 patients. Twenty-seven recurrences were firstly detected by ultrasonography, followed by CT or X-ray (10 cases in each). Types at the first recurrence were 5 cases in type-I, 8 in type-II and 18 in type-III. According to the modified classification, 3 patients in type I-1, 2 in type I-2, 1 in type II-1, 7 in type II-2, and 18 in type III. The mean MSTS score was 26.62 ± 4.21 (14-30). Neither Campanacci grade nor recurrence type, modified classification and other characters, were identified as risk factors. CONCLUSIONS: Soft tissue recurrence of GCTB may recur for more than once and distal radius was the most common location of primary GCTB that would suffer a soft tissue recurrence. Ultrasonography was a useful method to detect the recurrence. Since no risk factors were discovered, a careful follow-up with ultrasonography was recommended.

Role of albumin-bilirubin score in non-malignant liver disease.

The albumin-bilirubin (ALBI) score, which was proposed to assess the prognosis of patients with hepatocellular carcinoma, has gradually been extended to other liver diseases in recent years, including primary biliary cholangitis, liver cirrhosis, hepatitis, liver transplantation, and liver injury. The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models. It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators. An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease; additionally, it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases, such as decompensation events. This article presents a review of the application of ALBI scores in various non-malignant liver diseases.

Myositis-associated antibodies predict the severity of lung involvement in adult patients with inflammatory myositis - a cohort study of 70 adult patients with myositis in a single center.

Introduction: Idiopathic inflammatory myopathies (IIMs) encompass a diverse group of diseases characterized by considerable variability in clinical manifestations, antibody profiles, and responsiveness to immunosuppressive therapies. This study aimed to investigate the association between organ involvement and distinct myositis autoantibodies in individuals with IIM in a single-center cohort. Methods: Patients with ICD diagnoses M33.1, M33.2, M33.9, or M609 who (1) had been tested with Euroline blot assay for myositis autoantibodies and (2) met the classification criteria of definite/probable polymyositis (PM) or dermatomyositis (DM), anti-synthetase syndrome (ASS), or inclusion body myositis (IBM) were included. Medical journals were retrospectively examined with respect to clinical disease features. Results: Seventy patients (median age 58 years; 66% females) were included and represented the following diagnosis: PM (n = 23), DM (n = 21), ASS (n = 23), and IBM (n = 3). Most of the patients (87%) presented a muscle biopsy indicative of myositis. The presence of autoantibodies was as follows: myositis-specific antibodies, MSA (n = 53), myositis-associated antibodies, MAA (n = 33), both MSA + MAA (n = 24), MSA only (n = 29), MAA only (n = 9), no MSA, or MAA (n = 8). Anti-Jo-1 was the most common MSA (19%), whereas the most common MAA was anti-Ro/SSA52 (31%). We observed a significant association between antibody patterns and lung disease. In our cohort, 47% of the patients in the whole study group, 86% of patients with anti-SSA52, and 100% with anti-Jo-1 had pulmonary involvement. Patients with both MSA and MAA had a higher incidence of lung disease and decreased CO-diffusion capacity. This was especially prominent in anti-Ro/SSA52-positive patients. Interestingly, none of the patients suffered from lung disease if only antibodies against Mi-2α, Mi-2ß, NXP2, HMGCR, and TIF1γ were present or no MSA/MAA were detected. Discussion: The simultaneous presence of both MAA and MSA indicates an increased risk of lung involvement in patients with inflammatory myopathies. The presence of any MAA, and especially anti-Ro/SSA52, is associated with more severe pulmonary disease. Our data suggest that MAA antibodies might be relevant markers for early detection and treatment of lung involvement in IIM.

Association between plasma circulating tumor DNA and the prognosis of esophageal cancer patients: a meta-analysis.

BACKGROUND: The application of liquid biopsy analysis utilizing circulating tumor DNA (ctDNA) has gained prominence as a biomarker in specific cancer types. Nevertheless, the correlation between ctDNA and the prognostic outcomes of patients with esophageal cancer (EC) remains a subject of controversy. This meta-analysis aims to assess the correlation between ctDNA and the prognosis of EC patients. METHODS: We systematically explored Embase, PubMed, and the Cochrane Database to identify studies reporting on the prognostic value of ctDNA in EC patients before November 2023. The primary outcome involved the determine of associations between ctDNA with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS), as well asprogression-free survival (PFS) among EC patients. Secondary outcomes encompassed a detailed subgroup analysis in the setting of EC, including parameters such as detection time, histological subtypes, treatment modalities, regions, anatomic locations, and detection methods. Publication bias was assessed utilizing Begg's test, Egger's test, and funnel plots. A sensitivity analysis was conducted by systematically excluding individual studies to evaluate the stability of the results. RESULTS: A total of 1203 studies were initially screened, from which 13 studies underwent further analysis, encompassing 604 patients diagnosed with EC. The comprehensive pooled analysis indicated a significant association between the detection of ctDNA and poor OS (HR: 3.65; 95% CI: 1.97-6.75, P<0.001), DFS/RFS (HR: 6.08; 95% CI: 1.21-30.50, P<0.001), and PFS (HR: 2.84; 95% CI: 1.94-4.16, P<0.001). Subgroup analysis showed that ctDNA remained a consistent negative predictor of OS when stratified by different detection time, histological subtypes, regions, anatomic locations, and detection methods. Furthermore, subgroup analysis stratified by regions and study types demonstrated an association between ctDNA detection and poor PFS in EC patients. CONCLUSION: Our results indicate plasma ctDNA may serve as robust prognostic markers for OS, DFS/RFS, and PFS among EC patients. This finding suggests that plasma ctDNA could offer a highly effective approach for risk stratification and personalized medicine.

Inhibition of iron oxidation in Acidithiobacillus ferrooxidans by low-molecular-weight organic acids: Evaluation of performance and elucidation of mechanisms.

The catalytic role of Acidithiobacillus ferrooxidans (A. ferrooxidans) in iron biooxidation is pivotal in the formation of Acid Mine Drainage (AMD), which poses a significant threat to the environment. To control AMD generation, treatments with low-molecular-weight organic acids are being studied, yet their exact mechanisms are unclear. In this study, AMD materials, organic acids, and molecular methods were employed to gain a deeper understanding of the inhibitory effects of low-molecular-weight organic acids on the biooxidation of iron by A. ferrooxidans. The inhibition experiments of A. ferrooxidans on the oxidation of Fe2+ showed that to attain a 90 % inhibition efficacy within 72 h, the minimum concentrations required for formic acid, acetic acid, propionic acid, and lactic acid are 0.5, 6, 4, and 10 mmol/L, respectively. Bacterial imaging illustrated the detrimental effects of these organic acids on the cell envelope structure. This includes severe damage to the outer membrane, particularly from formic and acetic acids, which also caused cell wall damage. Coupled with alterations in the types and quantities of protein, carbohydrate, and nucleic acid content in extracellular polymeric substances (EPS), indicate the mechanisms underlying these inhibitory treatments. Transcriptomic analysis revealed interference of these organic acids with crucial metabolic pathways, particularly those related to energy metabolism. These findings establish a comprehensive theoretical basis for understanding the inhibition of A. ferrooxidans' biooxidation by low-molecular-weight organic acids, offering a novel opportunity to effectively mitigate the generation of AMD at its source.

Exosomes derived from diabetic serum accelerate the progression of osteoarthritis.

Diabetes mellitus (DM) has been demonstrated to accelerate the progression of osteoarthritis (OA) by largely unknown mechanisms. Studies have shown that DM dysfunctional adipocyte-derived exosomes play a crucial role in the pathogenesis of remote organ functions. The present study aimed to clarify whether and how diabetic adipocyte-derived exosomes mediate the pathological regulation of OA. We found that intraarticular injection of DM serum exosomes in the non-diabetic mice significantly exacerbated OA injury as evidenced by a rough and fractured cartilage surface as well as increased chondrocyte apoptosis, decreased mitochondrial membrane potential (△Ψ) and increased expression of cleaved caspase-3. Mechanistic investigation identified that miR-130b-3p was significantly increased in circulating exosomes derived from DM mice and exosomes derived from HG-treated normal adipocytes, and we demonstrated that transfection of miR-130b-3p mimics significantly exacerbated the mitochondrial function of chondrocytes. Our data also indicated that miR-130b-3p impaired the △Ψ, increased cleaved caspase-3 levels, and decreased the expression of 5'-adenosine monophosphate-activated protein kinase α1 (AMPKα1), Silent mating-type information regulation 2 homolog 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in chondrocytes. Pharmacologic activation of AMPKα1 using AICAR reversed the â–³Ψ and catabolic responses in chondrocytes transfected with miR-130b-3p mimics. Moreover, AICAR decreased the effects of miR-130b-3p mimics on chondrocytes transfected with SIRT1-siRNA or PGC-1α-siRNA. The current study demonstrated that adipocyte-derived exosomal miR-130b-3p under DM conditions suppresses mitochondrial function in chondrocytes through targeting the AMPKα1/SIRT1/PGC1-α pathway, thus exacerbating OA injury.

Effect of Dexmedetomidine on Intraoperative Hemodynamics and Blood Loss in Patients Undergoing Spine Surgery: A Systematic Review and Meta-Analysis.

Objective Dexmedetomidine (Dex) is a highly selective α2 adrenoceptor agonist that reduces blood pressure and heart rate. However, its ability to provide stable hemodynamics and a clinically significant reduction in blood loss in spine surgery is still a matter of debate. This study aimed to investigate the effects of Dex on intraoperative hemodynamics and blood loss in patients undergoing spine surgery.Methods The Web of Science, MEDLINE, EMBASE, and the Cochrane Library were searched up to February 2023 for randomized controlled trials (RCTs) including patients undergoing spine surgeries under general anaesthesia and comparing Dex and saline. A fixed- or random-effect model was used depending on heterogeneity.Results Twenty-one RCTs, including 1388 patients, were identified. Dex added the overall risk of intraoperative hypotension (odds ratio [OR]: 2.11; 95% confidence interval [CI]: 1.24 - 3.58; P=0.006) and bradycardia (OR: 2.48; 95%CI: 1.57 - 3.93; P=0.0001). The use of a loading dose of Dex led to significantly increased risks of intraoperative hypotension (OR: 2.00; 95%CI: 1.06 - 3.79; P=0.03) and bradycardia (OR: 2.28; 95%CI: 1.42 - 3.66; P=0.0007). For patients receiving total intravenous anesthesia, there was an increased risk of hypotension (OR: 2.90; 95%CI: 1.24 - 6.82; P=0.01) and bradycardia (OR: 2.66; 95%CI: 1.53 - 4.61; P=0. 0005). For patients in the inhalation anesthesia group, only an increased risk of bradycardia (OR: 4.95; 95%CI: 1.41 - 17.37; P=0.01) was observed. No significant increase in the risk of hypotension and bradycardia was found in the combined intravenous-inhalation anesthesia group. The incidence of severe hypotension (OR: 2.57; 95%CI: 1.05 - 6.32; P=0.04), but not mild hypotension, was increased. Both mild (OR: 2.55; 95%CI: 1.06 - 6.15; P=0.04) and severe (OR: 2.45; 95%CI: 1.43 - 4.20; P=0.001) bradycardia were associated with a higher risk. The overall analyses did not reveal significant reduction in intraoperative blood loss. However, a significant decrease in blood loss was observed in total inhalation anesthesia subgroup (mean difference [MD]: -82.97; 95%CI: -109.04 - -56.90; P<0.001).Conclusions Dex increases the risks of intraoperative hypotension and bradycardia in major spine surgery. The administration of a loading dose of Dex and the utilization of various anesthesia maintenance methods may potentially impact hemodynamic stability and intraoperative blood loss.

The CT-guided percutaneous drainage of pancreatic pseudocyst accompanied by pseudoaneurysm: A case report.

RATIONALE: This case report discusses the CT-guided percutaneous drainage of a pancreatic pseudocyst accompanied by a pseudoaneurysm. Pancreatic pseudocysts can erode the peripancreatic artery and produce pseudoaneurysms. This is rare, but it can be life-threatening. PATIENT CONCERNS: The case presented involves a 58-year-old female who was diagnosed with pancreatic cancer and underwent surgical treatment. She presented with hematochezia, dizziness, and hypodynamic findings with no obvious cause. Imaging revealed a pancreatic pseudocyst and small arterial aneurysms. To reduce the risk of aneurysm rupture, the patient underwent transcatheter arterial coil embolization. Three days later, CT-guided catheter drainage was performed to reduce the erosion of the arterial wall caused by pancreatic fluid. DIAGNOSES: The contrast-enhanced-CT imaging showed a round, slightly high-density lesion in the cyst, suggesting the presence of a pseudoaneurysm. INTERVENTIONS: The patient was sent for another transcatheter arterial embolization with coils and n-butyl-2-cyanoacrylate. OUTCOMES: After receiving the transcatheter arterial embolization, the patient had no serious bleeding or other complications. LESSONS: Early detection and accurate assessment of pseudoaneurysms are essential for appropriate management. This case shows that contrast-enhanced CT is necessary before CT-guided percutaneous drainage of pancreatic pseudocysts. It also shows that, due to the many complications that pancreatic pseudocysts may cause, appropriate treatment of pseudocysts complicated with pseudoaneurysm has important clinical significance.

Biocontrol and Growth Promotion Potential of Bacillus subtilis CTXW 7-6-2 against Rhizoctonia solani that Causes Tobacco Target Spot Disease.

Fungal diseases form perforated disease spots in tobacco plants, resulting in a decline in tobacco yield and quality. The present study investigated the antagonistic effect of Bacillus subtilis CTXW 7-6-2 against Rhizoctonia solani, its ability to promote the growth of tobacco seedlings, and the expression of disease resistance-related genes for efficient and eco-friendly plant disease control. Our results showed that CTXW 7-6-2 had the most vigorous growth after being cultured for 96 h, and its rate of inhibition of R. solani growth in vitro was 94.02%. The volatile compounds produced by CTXW 7-6-2 inhibited the growth of R. solani significantly (by 96.62%). The fungal growthinhibition rate of the B. subtilis CTXW 7-6-2 broth obtained after high-temperature and no-high-temperature sterile fermentation was low, at 50.88% and 54.63%, respectively. The lipopeptides extracted from the B. subtilis CTXW 7-6-2 fermentation broth showed a 74.88% fungal growth inhibition rate at a concentration of 100 mg/l. Scanning and transmission electron microscopy showed some organelle structural abnormalities, collapse, shrinkage, blurring, and dissolution in the R. solani mycelia. In addition, CTXW 7-6-2 increased tobacco seedling growth and improved leaf and root weight compared to the control. After CTXW 7-6-2 inoculation, tobacco leaves showed the upregulation of the PDF1.2, PPO, and PAL genes, which are closely related to target spot disease resistance. In conclusion, B. subtilis CTXW 7-6-2 may be an efficient biological control agent in tobacco agriculture and enhance plant growth potential.

Multifunctional chitosan-based lanthanide luminescent hydrogel with stretchability, adhesion, self-healing, color tunability and antibacterial ability.

Lanthanide luminescent hydrogels have broad application prospects in various fields. However, most of lanthanide hydrogels possess relatively simple functions, which is not conducive to practical applications. Therefore, it is becoming increasingly urgent to develop multifunctional hydrogels. Herein, a multifunctional chitosan-based lanthanide luminescent hydrogel with ultra-stretchability, multi-adhesion, excellent self-healing, emission color tunability, and good antibacterial ability was prepared by a simple one-step free radical polymerization. In this work, our designed lanthanide complexes [Ln(4-VDPA)3] contain three reaction sites, which can be copolymerized with N-[tris(hydroxymethyl) methyl] acrylamide (THMA), acrylamide (AM), and diacryloyl poly(ethylene glycol) (DPEG) to form the first chemical crosslinking network, while hydroxypropyltrimethyl ammonium chloride chitosan (HACC) interacts with the hydroxyl and amino groups derived from the chemical crosslinking network through hydrogen bonds to form the second physical crosslinking network. The structure of the double network as well as the dynamic hydrogen bond and lanthanide coordination endow the hydrogel with excellent stretchability, adhesion and self-healing properties. Moreover, the introduction of lanthanide complexes and chitosan makes the hydrogel exhibit outstanding luminescence and antibacterial performances. This research not only realizes the simple synthesis of multifunctional luminescent hydrogels, but also provides a new idea for the fabrication of biomass-based hydrogels as intelligent and sustainable materials.

Neoadjuvant savolitinib targeted therapy for stage IIIB-N3 lung adenocarcinoma harboring mesenchymal-epithelial transition exon 14 skipping mutation: a case report and literature review.

Savolitinib is a selective inhibitor that specifically targets the phosphorylation of mesenchymal-epithelial transition (MET) kinase. It has demonstrated significant inhibitory effects on the proliferation of tumor cells with METex14 skipping mutation, making it a promising treatment option. While it is the first approved small-molecule inhibitor specifically targeting MET kinase in China, there is limited information about its efficacy as neoadjuvant therapy for patients with supraclavicular lymph node metastasis (N3). In this case report, we presented the successful outcome of a 48-year-old male patient who was diagnosed with stage IIIB (T2bN3M0) lung adenocarcinoma originating from the left upper lobe. The patient exhibited the METex14 skipping alteration. Following two months of neoadjuvant savolitinib treatment, the patient achieved partial remission, with a significant reduction in the size of the primary tumor and metastatic lymph nodes. Postoperative pathological confirmation revealed a pathological complete response, and subsequent imaging examinations, including computed tomography scan and circulating tumor DNA-based molecular residual disease detection, showed no sign of recurrence at 7 months after surgery. Based on this case, neoadjuvant and adjuvant savolitinib therapy may be considered as a favorable alternative to chemotherapy for marginally resectable nonsmall cell lung cancer patients with METex14 skipping mutation.

Decreased PDLIM1 expression in endothelial cells contributes to the development of intracranial aneurysm.

INTRODUCTION: Intracranial aneurysm (IA) is a common vascular enlargement that occurs in the wall of cerebral vessels and frequently leads to fatal subarachnoid hemorrhage. PDZ and LIM domain protein 1 (PDLIM1) is a cytoskeletal protein that functions as a platform for multiple protein complex formation. However, whether PDLIM is involved in the pathogenesis of IA remains poorly understood. METHODS: Loss-of-function and gain-of-function strategies were employed to determine the in vitro roles of PDLIM1 in vascular endothelial cells (VECs). A rat model of IA was generated to study the role of PDLIM1 in vivo. Gene expression profiling, Western blotting, and dual luciferase reporter assays were performed to uncover the underlying cellular mechanism. Clinical IA samples were used to determine the expression of PDLIM1 and its downstream signaling molecules. RESULTS: PDLIM1 expression was reduced in the endothelial cells of IA and was regulated by Yes-associated protein 1 (YAP1). Genetic silencing of PDLIM1 inhibited the viability, migratory ability, and tube formation ability of VECs. Opposite results were obtained by ectopic expression of PDLIM1. Additionally, PDLIM1 overexpression mitigated IA in vivo. Mechanistic investigations revealed that PDLIM1 promoted the transcriptional activity of ß-catenin and induced the expression of v-myc myelocytomatosis viral oncogene homolog (MYC) and cyclin D1 (CCND1). In clinical settings, reduced expression of PDLIM1 and ß-catenin downstream target genes was observed in human IA samples. CONCLUSION: Our study indicates that YAP1-dependent expression of PDLIM1 can inhibit IA development by modulating the activity of the Wnt/ß-catenin signaling pathway and that PDLIM1 deficiency in VECs may represent a potential marker of aggressive disease.

[Mechanism of n-butanol fraction of Wenxia Formula combining with gefitinib in treating non-small cell lung cancer based on network pharmacology and in vitro experiment].

This study combined network pharmacology, molecular docking, and in vitro experiments to explore the potential mechanism of the active components of the n-butanol fraction of Wenxia Formula(NWXF) combined with gefitinib(GEF) in treating non-small cell lung cancer(NSCLC). Ultra-performance liquid chromatography-quadrupole Orbitrap mass spectrometry(UPLC-Q-Orbitrap MS) was employed to detect the main chemical components of NWXF. The active components of NWXF were retrieved from SwissADME, and the candidate targets of these active components were retrieved from SwissTargetPrediction. Online Mendelian Inheritance in Man(OMIM) and GeneCards were searched for the targets of NSCLC. Cytoscape 3.9.0 and STRING were employed to build the protein-protein interaction(PPI) network with the common targets shared by NWXF and NSCLC. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment were performed in DAVID to predict the potential mechanisms. Finally, molecular docking between the main active ingredients and key targets was conducted in SYBYL-X 2.0. The methyl thiazolyl tetrazolium(MTT) assay was employed to evaluate the inhibitory effects of NWXF and/or GEF on the proliferation of human non-small cell lung cancer cells(A549 and PC-9). Additionally, the impact of NWXF on human embryonic lung fibroblast cells(MRC-5) was assessed. The effectiveness of the drug combination was evaluated based on the Q value. The terminal-deoxynucleoitidyl transferase mediated nick-end labeling(TUNEL) assay was employed to examine the apoptosis of A549 and PC-9 cells treated with NWXF and/or GEF. Quantitative real-time PCR(qRT-PCR) was employed to measure the mRNA levels of epidermal growth factor receptor(EGFR), c-Jun N-terminal kinase(JNK), and Bcl2-associated X protein(Bax) in the A549 and PC-9 cells treated with NWXF and/or GEF. Western blot was employed to determine the protein levels of EGFR, p-EGFR, JNK, p-JNK, and Bax in the A549 and PC-9 cells treated with NWXF and/or GEF. A total of 77 active components, 488 potential targets, and 49 key targets involved in the treatment of NSCLC with NWXF were predicted. The results of GO annotation showed that NWXF may treat NSCLC by regulating the biological processes such as cell proliferation, apoptosis, and protein phosphorylation. KEGG enrichment revealed that the key targets of NWXF in treating NSCLC were enriched in the mitogen-activated protein kinase(MAPK), phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT), hypoxia-inducible factor-1(HIF-1), and microRNA-related signaling pathways. Molecular docking results showed that 91.9% of the docking scores were greater than 5, indicating the strong binding capability between main active components and key targets. The cell experiments demonstrated that NWXF combined with GEF synergistically inhibited the proliferation, promoted the apoptosis, decreased p-EGFR/EGFR and p-JNK/JNK values, down-regulated the mRNA levels of EGFR and JNK, and up-regulated the mRNA and protein levels of Bax in A549 and PC-9 cells. In conclusion, NWXF combined with GEF can regulate the EGFR/JNK pathway to promote the apoptosis of NSCLC cells, thus treating NSCLC.

Development and validation of a nomogram for Siewert II esophagogastric junction adenocarcinoma: a retrospective analysis.

Background: Due to the complex histological type and anatomical structures, there has been considerable debate on the classification of adenocarcinoma of the esophagogastric junction (AEG), especially Siewert II AEG. Furthermore, neither the American Joint Committee on Cancer (AJCC) 7th tumor-node-metastasis (TNM) [esophageal adenocarcinoma (E) or gastric cancer (G)] nor the AJCC 8th TNM (E or G) accurately predicted the prognosis of patients with Siewert II AEG. Objective: This study aimed to investigate the factors influencing the survival and prognosis of patients with Siewert II AEG and establish a new and better prognostic predictive model. Design: A retrospective study. Methods: Patients with Siewert II AEG, retrieved from the Surveillance, Epidemiology, and End Results (SEER) databases, were assigned to the training set. Patients retrieved from a single tertiary medical center were assigned to the external validation set. Significant variables were selected using univariate and multivariate Cox regression analyses to construct the nomogram. Nomogram models were assessed using the concordance index (C-index), a calibration plot, decision curve analysis (DCA), and external validation. Results: Age, tumor grade, and size, as well as the T, N, and M stages, were included in the nomograms. For the SEER training set, the C-index of the nomogram was 0.683 (0.665-0.701). The C-index of the nomogram for the external validation set was 0.690 (0.653-0.727). The calibration curve showed good agreement between the nomogram estimations and actual observations in both the training and external validation sets. The DCA showed that the nomogram was clinically useful. Conclusion: The new predictive model showed significant accuracy in predicting the prognosis of Siewert II AEG.

ABHD7-mediated depalmitoylation of lamin A promotes myoblast differentiation.

LMNA gene mutation can cause muscular dystrophy, and post-translational modification plays a critical role in regulating its function. Here, we identify that lamin A is palmitoylated at cysteine 522, 588, and 591 residues, which are reversely catalyzed by palmitoyltransferase zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) and depalmitoylase α/ß hydrolase domain 7 (ABHD7). Furthermore, the metabolite lactate promotes palmitoylation of lamin A by inhibiting the interaction between it and ABHD7. Interestingly, low-level palmitoylation of lamin A promotes, whereas high-level palmitoylation of lamin A inhibits, murine myoblast differentiation. Together, these observations suggest that ABHD7-mediated depalmitoylation of lamin A controls myoblast differentiation.

Prognostic and metabolic characteristics of a novel cuproptosis-related signature in patients with hepatocellular carcinoma.

Cuproptosis is a novel discovered mode of programmed cell death. To identify the molecular regulatory patterns related to cuproptosis, this study was designed for exploring the correlation between cuproptosis-related genes (CRGs) and the prognosis, metabolism, and treatment of hepatocellular carcinoma (HCC). Cancer Genome Atlas (TCGA) database was used to screen 363 HCC samples, which were categorized into 2 clusters based on the expression of CRGs. Survival analysis demonstrated that overall survival (OS) was better in Cluster 1 than Cluster 2 which might to be relevant to differences in metabolic based on functional analysis. With LASSO regression analysis and univariate COX regression, 8 prognosis-related genes were screened, a differently expressed genes (DEGs) were then constructed (HCC patients' DEGs)-based signature. The signature's stability was also validated in the 2 independent cohorts and test cohorts (GSE14520, HCC dataset in PCAWG). The 1-year, 3-year, and 5-year area under the curve (AUC) were 0.756, 0.706, and 0.722, respectively. The signature could also well predict the response to chemotherapy, targeted and transcatheter arterial chemoembolization (TACE) by providing a risk score. Moreover, the correlation was uncovered by the research between the metabolism and risk score. In conclusion, a unique cuproptosis-related signature that be capable of predicting patients' prognosis with HCC, and offered valuable insights into chemotherapy, TACE and targeted therapies for these patients has been developed.