Conversion therapy of a giant hepatocellular carcinoma with portal vein thrombus and inferior vena cava thrombus: A case report and review of literature.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) combined with portal and hepatic vein cancerous thrombosis is poor, for unresectable patients the combination of targeted therapy and immune therapy was the first-line recommended treatment for advanced HCC, with a median survival time of only about 2.7-6 months. In this case report, we present the case of a patient with portal and hepatic vein cancerous thrombosis who achieved pathologic complete response after conversion therapy. CASE SUMMARY: In our center, a patient with giant HCC combined with portal vein tumor thrombus and hepatic vein tumor thrombus was treated with transcatheter arterial chemoembolization (TACE), radiotherapy, targeted therapy and immunotherapy, and was continuously given icaritin soft capsules for oral regulation. After 7 months of conversion therapy, the patient's tumor shrank and the tumor thrombus subsided significantly. The pathology of surgical resection was in complete remission, and there was no progression in the postoperative follow-up for 7 months, which provided a basis for the future strategy of combined conversion therapy. CONCLUSION: In this case, atezolizumab, bevacizumab, icaritin soft capsules combined with radiotherapy and TACE had a good effect. For patients with hepatocellular carcinoma combined with hepatic vein/inferior vena cava tumor thrombus, adopting a high-intensity, multimodal proactive strategy under the guidance of multidisciplinary team (MDT) is an important attempt to break through the current treatment dilemma.

Disulfide bonds as a molecular switch of enzyme-activatable anticancer drug precise release for fluorescence imaging and enhancing tumor therapy.

Enzyme-activatable drug delivery systems have been developed for cancer diagnosis and therapy. However, targeted intracellular drug delivery is a challenge for precisely tumor imaging and therapy due to the increased stability of copolymer nanoparticles (NPs) is accompanied by a notable decrease in enzyme degradation. Herein, disulfide bond was designed as an enzyme-activatable molecular switch of SS-P(G2)2/DOX NPs. The copolymer NPs consists of polyvinylpyrrolidone (PVP) with disulfide bonds in the center and enzyme-degradable peptide dendrites (Phe-Lys) to form dendritic-linear-dendritic triblock copolymers (TBCs). The amphiphilic TBCs could be split into two identical amphiphilic diblock copolymers (DBCs) by glutathione (GSH) in cancer cells specifically while maintaining the same hydrophilic-lipophilic equilibrium. This structural transformation significantly reduced the stability of copolymer NPs and enhanced sensitivity of DOX release by cathepsin B-activated. Subsequently, the released DOX acted as an indicator of fluorescence imaging and chemotherapy drug for cancer cells. The polymeric NPs achieved excellent drug-loaded stability and prolonged blood circulation in vivo, and realized fluorescence imaging and specific cancer cell killing capabilities by responding to the overexpression of GSH and cathepsin B in tumor cells. Furthermore, the copolymer NPs demonstrated excellent blood compatibility and biosafety. Therefore, a novel strategy based on one tumor marker acting as the switch for another tumor microenvironment responsive drug delivery system could be designed for tumor intracellular imaging and chemotherapy.

Functional and Genetic Analyses Unveil the Implication of CDC27 in Hemifacial Microsomia.

Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible, external ear, and middle ear. The pathogenic genes remain largely unidentified. Whole-exome sequencing (WES) was conducted on 12 HFM probands and their unaffected biological parents. Predictive structural analysis of the target gene was conducted using PSIPRED (v3.3) and SWISS-MODEL, while STRING facilitated protein-to-protein interaction predictions. CRISPR/Cas9 was applied for gene knockout in zebrafish. In situ hybridization (ISH) was employed to examine the spatiotemporal expression of the target gene and neural crest cell (NCC) markers. Immunofluorescence with PH3 and TUNEL assays were used to assess cell proliferation and apoptosis. RNA sequencing was performed on mutant and control embryos, with rescue experiments involving target mRNA injections and specific gene knockouts. CDC27 was identified as a novel candidate gene for HFM, with four nonsynonymous de novo variants detected in three unrelated probands. Structural predictions indicated significant alterations in the secondary and tertiary structures of CDC27. cdc27 knockout in zebrafish resulted in craniofacial malformation, spine deformity, and cardiac edema, mirroring typical HFM phenotypes. Abnormalities in somatic cell apoptosis, reduced NCC proliferation in pharyngeal arches, and chondrocyte differentiation issues were observed in cdc27-/- mutants. cdc27 mRNA injections and cdkn1a or tp53 knockout significantly rescued pharyngeal arch cartilage dysplasia, while sox9a mRNA administration partially restored the defective phenotypes. Our findings suggest a functional link between CDC27 and HFM, primarily through the inhibition of CNCC proliferation and disruption of pharyngeal chondrocyte differentiation.

Nucleolin lactylation contributes to intrahepatic cholangiocarcinoma pathogenesis via RNA splicing regulation of MADD.

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a fatal malignancy of the biliary system. The lack of a detailed understanding of oncogenic signaling or global gene expression alterations has impeded clinical iCCA diagnosis and therapy. The role of protein lactylation, a newly unraveled post-translational modification that orchestrates gene expression, remains largely elusive in the pathogenesis of iCCA. METHODS: Proteomics analysis of clinical iCCA specimens and adjacent tissues was performed to screen for proteins aberrantly lactylated in iCCA. Mass spectrometry, macromolecule interaction and cell behavioral studies were employed to identify the specific lactylation sites on the candidate protein(s) and to decipher the downstream mechanisms responsible for iCCA development, which were subsequently validated using a xenograft tumor model and clinical samples. RESULTS: Nucleolin (NCL), the most abundant RNA-binding protein in the nucleolus, was identified as a functional lactylation target that correlates with iCCA occurrence and progression. NCL was lactylated predominantly at lysine 477 by the acyltransferase P300 in response to a hyperactivity of glycolysis, and promoted the proliferation and invasion of iCCA cells. Mechanistically, lactylated NCL bound to the primary transcript of MAP kinase-activating death domain protein (MADD) and led to efficient translation of MADD by circumventing alternative splicing that generates a premature termination codon. NCL lactylation, MADD translation and subsequent ERK activation promoted xenograft tumor growth and were associated with overall survival in patients with iCCA. CONCLUSION: NCL is lactylated to upregulate MADD through an RNA splicing-dependent mechanism, which potentiates iCCA pathogenesis via the MAPK pathway. Our findings reveal a novel link between metabolic reprogramming and canonical tumor-initiating events, and uncover biomarkers that can potentially be used for prognostic evaluation or targeted treatment of iCCA. IMPACT AND IMPLICATIONS: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive liver malignancy with largely uncharacterized pathogenetic mechanisms. Herein, we demonstrated that glycolysis promotes P300-catalyzed lactylation of nucleolin, which upregulates MAP kinase-activating death domain protein (MADD) through precise mRNA splicing and activates ERK signaling to drive iCCA development. These findings unravel a novel link between metabolic rewiring and canonical oncogenic pathways, and reveal new biomarkers for prognostic assessment and targeting of clinical iCCA.

Hearing outcomes following cochlear implantation with anatomic or default frequency mapping in postlingual deafness adults.

PURPOSE: The aim of this study was to compare the outcomes of different mapping procedures based on anatomic or default frequency distribution in postlingual deafness adults who underwent cochlear implantation (CI). METHODS: Forty-eight adults with postlingual deafness who underwent CI (MED-EL) from January 2021 to May 2022 in our hospital were prospectively recruited. The participants were randomly assigned to two groups (the anatomic group and the default group). Postoperative computerized tomography (CT) scans were evaluated with Otoplan® to determine the angular insertion depth (AID) and the specific locations of the intracochlear electrodes. Anatomic maps were imported into MAESTRO 9.0 software (MED-EL) for anatomy-based fitting for anatomic group, while default mapping program was set up for the default group. Hearing thresholds, Speech Recognition Scores (SRS), and subjects' auditory and musical abilities were evaluated 1 year after using the CI. Differences were determined in two groups using Stata statistical software, with significance defined as p < 0.05. RESULTS: SRS under noisy conditions was significantly greater for anatomic group than the default group (p = 0.02). Under quiet conditions, however, mean hearing thresholds (0.5, 1, 2, and 4 kHz) and SRS did not differ significantly between the two groups (p = 0.07). Modified questionnaires showed that auditory (p = 0.02) and musical (p = 0.01) quality were significantly better following the anatomic mapping than the default procedure. CONCLUSION: CI program based on the anatomic distribution may bring better SRS under noise conditions as well as better auditory and musical qualities than based on the default frequency distribution.

Co-Occurrence of Sensorineural Hearing Loss and Congenital Heart Disease: Etiologies and Management.

OBJECTIVES/HYPOTHESIS: The co-occurrence of sensorineural hearing loss (SNHL) and congenital heart disease (CHD) is a rare condition with complex etiologies. The purpose of this study is to assess the etiologies, clinical features, and outcomes of cochlear implant (CI) in this patient population. STUDY DESIGN: Case series and literature review. METHODS: Clinical data of children who were diagnosed with SNHL and CHD and received CIs at a tertiary hospital from 2016 to 2021 were retrospectively analyzed. A literature review was performed to identify patients with SNHL and CHD. FINDINGS: Of the 382 children who underwent cochlear implantation at our center, eight (2.1%) were diagnosed with SNHL and CHD. A literature review identified 1525 patients from 254 studies; the database therefore consisted of 1533 patients. The most common genetic etiologies of co-occurring SNHL and CHD were CHARGE syndrome (36.3%), Turner syndrome (8.4%), 22q11.2 deletion (3.0%), Noonan syndrome (2.9%), and Down syndrome (2.5%), whereas the most common non-genetic etiologies were congenital rubella syndrome (22.9%) and SNHL after early cardiac surgery (5.5%). Most of the patients presented with congenital, bilateral, severe-profound SNHL requiring early rehabilitation. Of the 126 children who received CIs at a median age of 2.5 years, half showed delayed speech development at last follow-up. CONCLUSIONS: Co-occurring SNHL and CHD is a rare condition with complex etiologies. Timely hearing intervention with long-term follow-up and proper timing of heart surgery is essential for these children. LEVEL OF EVIDENCE: 4, case series Laryngoscope, 134:400-409, 2024.

Artificial intelligence for colorectal neoplasia detection during colonoscopy: a systematic review and meta-analysis of randomized clinical trials.

Background: The use of artificial intelligence (AI) in detecting colorectal neoplasia during colonoscopy holds the potential to enhance adenoma detection rates (ADRs) and reduce adenoma miss rates (AMRs). However, varied outcomes have been observed across studies. Thus, this study aimed to evaluate the potential advantages and disadvantages of employing AI-aided systems during colonoscopy. Methods: Using Medical Subject Headings (MeSH) terms and keywords, a comprehensive electronic literature search was performed of the Embase, Medline, and the Cochrane Library databases from the inception of each database until October 04, 2023, in order to identify randomized controlled trials (RCTs) comparing AI-assisted with standard colonoscopy for detecting colorectal neoplasia. Primary outcomes included AMR, ADR, and adenomas detected per colonoscopy (APC). Secondary outcomes comprised the poly missed detection rate (PMR), poly detection rate (PDR), and poly detected per colonoscopy (PPC). We utilized random-effects meta-analyses with Hartung-Knapp adjustment to consolidate results. The prediction interval (PI) and I2 statistics were utilized to quantify between-study heterogeneity. Moreover, meta-regression and subgroup analyses were performed to investigate the potential sources of heterogeneity. This systematic review and meta-analysis is registered with PROSPERO (CRD42023428658). Findings: This study encompassed 33 trials involving 27,404 patients. Those undergoing AI-aided colonoscopy experienced a significant decrease in PMR (RR, 0.475; 95% CI, 0.294-0.768; I2 = 87.49%) and AMR (RR, 0.495; 95% CI, 0.390-0.627; I2 = 48.76%). Additionally, a significant increase in PDR (RR, 1.238; 95% CI, 1.158-1.323; I2 = 81.67%) and ADR (RR, 1.242; 95% CI, 1.159-1.332; I2 = 78.87%), along with a significant increase in the rates of PPC (IRR, 1.388; 95% CI, 1.270-1.517; I2 = 91.99%) and APC (IRR, 1.390; 95% CI, 1.277-1.513; I2 = 86.24%), was observed. This resulted in 0.271 more PPCs (95% CI, 0.144-0.259; I2 = 65.61%) and 0.202 more APCs (95% CI, 0.144-0.259; I2 = 68.15%). Interpretation: AI-aided colonoscopy significantly enhanced the detection of colorectal neoplasia detection, likely by reducing the miss rate. However, future studies should focus on evaluating the cost-effectiveness and long-term benefits of AI-aided colonoscopy in reducing cancer incidence. Funding: This work was supported by the Heilongjiang Provincial Natural Science Foundation of China (LH2023H096), the Postdoctoral research project in Heilongjiang Province (LBH-Z22210), the National Natural Science Foundation of China's General Program (82072640) and the Outstanding Youth Project of Heilongjiang Natural Science Foundation (YQ2021H023).

Construction of lncRNA-miRNA-mRNA regulatory network in severe asthmatic bronchial epithelial cells: A bioinformatics study.

Asthma is a chronic respiratory disease caused by environment-host interactions. Bronchial epithelial cells (BECs) are the first line of defense against environmental toxins. However, the mechanisms underlying the role of BECs in severe asthma (SA) are not yet fully understood. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been shown to play important roles in the regulation of gene expression in the pathogenesis of SA. In this study, bioinformatics was used for the first time to reveal the lncRNA-miRNA-mRNA regulatory network of BECs in SA. Five mRNA datasets of bronchial brushing samples from patients with SA and healthy controls (HC) were downloaded from the Gene Expression Omnibus (GEO) database. A combination of the Venn diagram and robust rank aggregation (RRA) method was used to identify core differentially expressed genes (DEGs). Protein-protein interaction (PPI) analysis of core DEGs was performed to screen hub genes. The miRDB, miRWalk, and ENCORI databases were used to predict the miRNA-mRNA relationships, and the ENCORI and starBase v2.0 databases were used to predict the upstream lncRNAs of the miRNA-mRNA relationships. Four core DEGs were identified: carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), interleukin-1 receptor type 2 (IL1R2), trefoil factor 3 (TFF3), and vascular endothelial growth factor A (VEGFA). These 4 core DEGs indicated that SA was not significantly associated with sex. Enrichment analysis showed that the MAPK, Rap1, Ras, PI3K-Akt and Calcium signaling pathways may serve as the principal pathways of BECs in SA. A lncRNA-miRNA-mRNA regulatory network of the severe asthmatic bronchial epithelium was constructed. The top 10 competing endogenous RNAs (ceRNAs) were FGD5 antisense RNA 1 (FGD5-AS1), metastasis associated lung adenocarcinoma transcript 1 (MALAT1), X inactive specific transcript (XIST), HLA complex group 18 (HCG18), small nucleolar RNA host gene 16 (SNHG16), has-miR-20b-5p, has-miR-106a-5p, hsa-miR-106b-5p, has-miR-519d-3p and Fms related receptor tyrosine kinase 1 (FLT1). Our study revealed a potential mechanism for the lncRNA-miRNA-mRNA regulatory network in BECs in SA.

Characteristics and Clinical Outcomes After Osteochondral Allograft Transplantation for Treating Articular Cartilage Defects: Systematic Review and Single-Arm Meta-analysis of Studies From 2001 to 2020.

Background: Osteochondral allograft transplantation (OCA) treats symptomatic focal cartilage defects with satisfactory clinical results. Purpose: To comprehensively analyze the characteristics and clinical outcomes of OCA for treating articular cartilage defects. Study Design: Systematic review; Level of evidence, 4. Methods: We searched Embase, PubMed, Cochrane Database, and Web of Science for studies published between January 1, 2001, and December 31, 2020, on OCA for treating articular cartilage defects. Publication information, patient data, osteochondral allograft storage details, and clinical outcomes were extracted to conduct a comprehensive summative analysis. Results: In total, 105 studies involving 5952 patients were included. The annual reported number of patients treated with OCA increased from 69 in 2001 to 1065 in 2020, peaking at 1504 cases in 2018. Most studies (90.1%) were performed in the United States. The mean age at surgery was 34.2 years, and 60.8% of patients were male and had a mean body mass index of 26.7 kg/m2. The mean lesion area was 5.05 cm2, the mean follow-up duration was 54.39 months, the mean graft size was 6.85 cm2, and the number of grafts per patient was 54.7. The failure rate after OCA was 18.8%, and 83.1% of patients reported satisfactory results. Allograft survival rates at 2, 5, 10, 15, 20, and 25 years were 94%, 87.9%, 80%, 73%, 55%, and 59.4%, respectively. OCA was mainly performed on the knee (88.9%). The most common diagnosis in the knee was osteochondritis dissecans (37.9%), and the most common defect location was the medial femoral condyle (52%). The most common concomitant procedures were high tibial osteotomy (28.4%) and meniscal allograft transplantation (24.7%). After OCA failure, 54.7% of patients underwent revision with primary total knee arthroplasty. Conclusion: The annual reported number of patients who underwent OCA showed a significant upward trend, especially from 2016 to 2020. Patients receiving OCA were predominantly young male adults with a high body mass index. OCA was more established for knee cartilage than an injury at other sites, and its best indication was osteochondritis dissecans. This analysis demonstrated satisfactory long-term postoperative outcomes.

Research trends and hotspots of exosomes in respiratory diseases.

Currently, theoretical studies on exosomes in respiratory diseases have received much attention from many scholars and have made remarkable progress, which has inestimable value and potential in future clinical and scientific research. Unfortunately, no scholar has yet addressed this field's bibliometric analysis and summary. We aim to comprehensively and profoundly study and explore the present situation and highlights of exosome research at the stage of respiratory diseases and to provide meaningful insights for the future development of this field. The WOSCC literature was gathered for the study using bibliometrics, and the data were collected and analyzed using CiteSpace, VOSviewer, Microsoft Excel, and Endnote software. The publication language is "English," and the search strategy is TS = (exosome OR exosomes OR exosomal) AND TS = (respiratory OR lung). The search time is from the beginning of the WOS construction, and the deadline is July 11, 2022, at 22:00 hours. The literature types selected were dissertation, review paper, and online published paper. The analysis includes 2456 publications in 738 journals from 76 countries, 2716 institutions, and 14,568 authors. The field's annual publications have been rising, especially in recent years. China and the US lead research, and prominent universities, including Harvard Medical School, Shanghai Jiao Tong University, and Fudan University, are essential research institutes. Takahiro Ochiya, whose research focuses on exosomes and lung cancer, and Clotilde Théry, a pioneering exosome researcher, are the most cited authors in this field. The key terms include lung cancer, non-small cell lung cancer, mesenchymal stem cells, intercellular communication, exosomal miRNAs, and oncology. Cell biology, biochemistry & biotechnology, and oncology are related fields. The final summary of research hotspots is exosomes and lung cancer, mesenchymal stem cell-derived exosomes and lung inflammation, and miRNAs in exosomes as biomarkers for respiratory illnesses. The present research situation and relevant hotspots of the area were analyzed through bibliometric studies on exosomes in respiratory diseases. The research development in this field has a considerable upside, and the exosome's function in diagnosing, treating, monitoring, and prognosis of respiratory illnesses cannot be taken lightly. Moreover, we believe the research results will bring the gospel to many patients with clinical respiratory diseases shortly.

Enzyme and pH dual responsive linear-dendritic block copolymer micelles based on a phenylalanyl-lysine motif and peripherally ketal-functionalized dendron as potential drug carriers.

Stimuli-responsive linear-dendritic block copolymers (LDBCs) have attracted significant research attention as novel drug carriers. We report here three generations of new enzyme and pH dual responsive linear-dendritic block copolymers (LDBCs) with a phenylalanyl-lysine (Phe-Lys) dipeptide linking hydrophilic linear poly(N-vinylpyrrolidone) (PNVP) and a hydrophobic peripherally ketal-functionalized dendron derived from 2,2'-bis(hydroxymethyl)propionic acid (bis-MPA). The LDBCs are synthesized via a combination of interchange of xanthates/reversible addition-fragmentation chain transfer (MADIX/RAFT) polymerization of N-vinylpyrrolidone (NVP) and "chain-first" strategy. Their structures are confirmed by 1H NMR spectra. The gel permeation chromatograph (GPC) analysis revealed that the LDBCs have a narrow molecular weight distribution (PDI ≤ 1.25). The amphiphilic LDBCs can self-assemble into spherical nanomicelles in aqueous solution. The presence of enzyme or/and the change of pH cause disassembly of micelles to release encapsulated cargos. The release rates of the guest molecules are faster in buffer solution at pH 5.0 than those upon the addition of the activating enzyme and can be fine-tuned by changing the generation of bis-MPA dendrons. The combination of enzyme and pH dual stimuli results in significantly accelerated and more complete release of the loaded hydrophobic guests. The cell viability assay confirmed the favorable biocompatibility until the LDBC micelle concentration reached 800 µg mL-1. These results indicate that the LDBCs can be considered as a good candidate for targeting drug delivery.

Biological and genomic analysis of a symbiotic nitrogen fixation defective mutant in Medicago truncatula.

Medicago truncatula has been selected as one of the model legume species for gene functional studies. To elucidate the functions of the very large number of genes present in plant genomes, genetic mutant resources are very useful and necessary tools. Fast Neutron (FN) mutagenesis is effective in inducing deletion mutations in genomes of diverse species. Through this method, we have generated a large mutant resource in M. truncatula. This mutant resources have been used to screen for different mutant using a forward genetics methods. We have isolated and identified a large amount of symbiotic nitrogen fixation (SNF) deficiency mutants. Here, we describe the detail procedures that are being used to characterize symbiotic mutants in M. truncatula. In recent years, whole genome sequencing has been used to speed up and scale up the deletion identification in the mutant. Using this method, we have successfully isolated a SNF defective mutant FN007 and identified that it has a large segment deletion on chromosome 3. The causal deletion in the mutant was confirmed by tail PCR amplication and sequencing. Our results illustrate the utility of whole genome sequencing analysis in the characterization of FN induced deletion mutants for gene discovery and functional studies in the M. truncatula. It is expected to improve our understanding of molecular mechanisms underlying symbiotic nitrogen fixation in legume plants to a great extent.

Identifying immune infiltration by deep learning to assess the prognosis of patients with hepatocellular carcinoma.

BACKGROUND: The treatment situation for hepatocellular carcinoma remains critical. The use of deep learning algorithms to assess immune infiltration is a promising new diagnostic tool. METHODS: Patient data and whole slide images (WSIs) were obtained for the Xijing Hospital (XJH) cohort and TCGA cohort. We wrote programs using Visual studio 2022 with C# language to segment the WSI into tiles. Pathologists classified the tiles and later trained deep learning models using the ResNet 101V2 network via ML.NET with the TensorFlow framework. Model performance was evaluated using AccuracyMicro versus AccuracyMacro. Model performance was examined using ROC curves versus PR curves. The percentage of immune infiltration was calculated using the R package survminer to calculate the intergroup cutoff, and the Kaplan‒Meier method was used to plot the overall survival curve of patients. Cox regression was used to determine whether the percentage of immune infiltration was an independent risk factor for prognosis. A nomogram was constructed, and its accuracy was verified using time-dependent ROC curves with calibration curves. The CIBERSORT algorithm was used to assess immune infiltration between groups. Gene Ontology was used to explore the pathways of differentially expressed genes. RESULTS: There were 100 WSIs and 165,293 tiles in the training set. The final deep learning models had an AccuracyMicro of 97.46% and an AccuracyMacro of 82.28%. The AUCs of the ROC curves on both the training and validation sets exceeded 0.95. The areas under the classification PR curves exceeded 0.85, except that of the TLS on the validation set, which might have had poor results (0.713) due to too few samples. There was a significant difference in OS between the TIL classification groups (p < 0.001), while there was no significant difference in OS between the TLS groups (p = 0.294). Cox regression showed that TIL percentage was an independent risk factor for prognosis in HCC patients (p = 0.015). The AUCs according to the nomogram were 0.714, 0.690, and 0.676 for the 1-year, 2-year, and 5-year AUCs in the TCGA cohort and 0.756, 0.797, and 0.883 in the XJH cohort, respectively. There were significant differences in the levels of infiltration of seven immune cell types between the two groups of samples, and gene ontology showed that the differentially expressed genes between the groups were immune related. Their expression levels of PD-1 and CTLA4 were also significantly different. CONCLUSION: We constructed and tested a deep learning model that evaluates the immune infiltration of liver cancer tissue in HCC patients. Our findings demonstrate the value of the model in assessing patient prognosis, immune infiltration and immune checkpoint expression levels.

A scalable and anti-fouling silver-nickel/cellulose paper with synergy photothermal effect for efficient solar distillation.

Solar interfacial evaporation is one of the most efficient and environmentally-friendly clean freshwater production technologies. Plasma metal nanoparticles are excellent optical absorption materials, but their high cost and inherent resonance narrow bandwidth absorption limit their application. In this work, commercial cellulose papers are used as substrates to synthesize Ag-Ni/cellulose paper by the seed-mediated method. The Ag-Ni/cellulose paper exhibits high light absorption at the full wavelength (200-2500 nm) resulting from the synergistic effect of localized surface plasmon resonance (LSPR) of Ag NPs and the interband transitions (IBTs) of Ni. Under one-sun irradiation (1 kW m-2), the energy utilization efficiency of Ag-Ni/cellulose paper is as high as 93.8%, and the water evaporation rate is 1.87 kg m-2 h-1. Diffusion inhibition experiment results show that the Ag-Ni/cellulose paper exhibits excellent antibacterial performance, and the antibacterial performance is highly related with Ag NPs content. These provide new opportunities for commercial production of competitive cost, green, and portable solar evaporators for different application sceneries.

Dissection of insular cortex layer 5 reveals two sublayers with opposing modulatory roles in appetitive drinking behavior.

The insular cortex (insula) is known to play a modulatory role in feeding and drinking. Previous studies have revealed anterior-posterior differences of subcortical projections and roles for the insula, yet the anatomical and functional heterogeneity among the cortical layers remains poorly understood. Here, we show that layer 5 of the mouse dysgranular insula has two distinct neuronal subpopulations along the entire anterior-posterior axis: The L5a population, expressing NECAB1, projects bilaterally to the lateral and capsular divisions of the central amygdala, and the L5b population, expressing CTIP2, projects ipsilaterally to the parasubthalamic nucleus and the medial division of the central amygdala. Optogenetically activating L5a and L5b neuronal populations in thirsty male mice led to suppressed and facilitated water spout licking, respectively, without avoidance against or preference for the spout paired with the opto-stimulation. Our results suggest sublayer-specific bidirectional modulatory roles of insula layer 5 in the motivational aspect of appetitive behavior.

Titanium alloy cannulated screws and biodegrade ceramic nails for treatment of femoral neck fractures: A finite element analysis.

BACKGROUND: Our previous studies have demonstrated the mechanical effect of sclerosis around screw paths on the healing of femoral neck fractures (FNF) after internal fixation. Furthermore, we discussed the possibility of using bioceramic nails (BNs) to prevent sclerosis. However, all these studies were conducted under static conditions as the patient was standing on one leg, while the effect of the stress generated during movement is unknown. The purpose of this study was to evaluate the stress and displacement under dynamic stress loading conditions. METHODS: Two types of internal fixation, namely cannulated screws and bioceramic nails, were utilized in conjunction with various finite element models of the femur. These models included the femoral neck fracture healing model, the femoral neck fracture model, and the sclerosis around screws model. The resulting stress and displacement were analyzed by applying the contact forces associated with the most demanding activities during gait, including walking, standing, and knee bending. The present study establishes a comprehensive framework for investigating the biomechanical properties of internal fixation devices in the context of femoral fractures. RESULTS: The stress at the top of the femoral head in the sclerotic model was increased by roughly 15 MPa during the knee bend and walking phases and by about 30 MPa during the standing phase compared to the healing model. The area of high stress at the top of the femoral head was increased during the sclerotic model's walking and standing phases. Additionally, the stress distribution throughout the dynamic gait cycle was comparable before and after the removal of internal fixations following the healing of the FNF. The overall stress distribution of the entire fractured femoral model was lower and more evenly distributed in all combinations of internal fixation. Furthermore, the internal fixation stress concentration was lower when more BNs were used. In the fractured model with three cannulated screws (CSs), however, the majority of the stress was concentrated around the ends of the fractures.The maximal stress in the healing model with one CS and two BNs was the highest at all stages of gait over three combinations of internal fixation, and the stress was mainly carried by CS. CONCLUSIONS: The presence of sclerosis around screw paths increases the risk of femoral head necrosis. Removal of CS has little effect on the mechanics of the femur after healing of the FNF. BNs have several advantages over conventional CSs after FNF. Replacing all internal fixations with BNs after the healing of FNF may solve the problem of sclerosis formation around CSs to improve bone reconstruction owing to their bioactivity.

[Systematic evaluation of the incidence of the knee donor area after autobone cartilage mosaic xentoplasty].

OBJECTIVE: To provide an overview of the incidence of knee donor -site morbidity after autologous osteochondral mosaicplasty. METHODS: A comprehensive search was conducted in PubMed, EMbase, Wanfang Medical Network, and CNKI databases from January 2010 to April 20, 2021. Relevant literature was selected based on predefined inclusion and exclusion criteria, and data were evaluated and extracted. The correlation between the number and size of transplanted osteochondral columns and donor-site morbidity was analyzed. RESULTS: A total of 13 literatures were included, comprising a total of 661 patients. Statistical analysis revealed an incidence of knee donor-site morbidity at 8.6% (57/661), with knee pain being the most common complaint, accounting for 4.2%(28/661). There was no significant correlation between the number of osteochondral columns and postoperative donor-site incidence (P=0.424, N=10), nor between the diameter size of osteochondral columns and postoperative donor-site incidence(P=0.699, N=7). CONCLUSION: Autologous osteochondral mosaicplasty is associated with a considerable incidence of knee donor-site morbidity, with knee pain being the most frequent complaint. There is no apparent correlation between donor-site incidence and the number and size of transplanted osteochondral columns. Donors should be informed about the potential risks.

Risk factors analysis of surgical complications of hepatic hemangioma: a modified Clavien-Dindo classification-based study.

PURPOSE: There are few studies on the risk factors of postoperative complications after surgical treatment of hepatic hemangioma (HH). This study aims to provide a more scientific reference for clinical treatment. METHODS: The clinical characteristics and operation data of HH patients undergoing surgical treatment in the First Affiliated Hospital of Air Force Medical University from January 2011 to December 2020 were retrospectively collected. All enrolled patients were divided into two groups based on the modified Clavien-Dindo classification: Major group (Grade II/III/IV/V) and Minor group (Grade I and no complications). Univariate and multivariate regression analysis was used to explore the risk factors for massive intraoperative blood loss (IBL) and postoperative Grade II and above complications. RESULTS: A total of 596 patients were enrolled, with a median age of 46.0 years (range, 22-75 years). Patients with Grade II/III/IV/V complications were included in the Major group (n = 119, 20%), and patients with Grade I and no complications were included in the Minor group (n = 477, 80%). The results of multivariate analysis of Grade II/III/IV/V complications showed that operative duration, IBL, and tumor size increased the risk of Grade II/III/IV/V complications. Conversely, serum creatinine (sCRE) decreased the risk. The results of multivariate analysis of IBL showed that tumor size, surgical method, and operative duration increased the risk of IBL. CONCLUSIONS: Operative duration, IBL, tumor size, and surgical method are independent risk factors that should be paid attention to in HH surgery. In addition, as an independent protective factor for HH surgery, sCRE should attract more attention from scholars.

A COMPARATIVE ANALYSIS TO DETERMINE THE OPTIMUM HISTONE DEACETYLASE INHIBITORS AND ADMINISTRATION ROUTE FOR IMPROVING SURVIVAL AND ORGAN INJURY IN RATS AFTER HEMORRHAGIC SHOCK.

ABSTRACT: Objective: Histone deacetylase inhibitors (HDACIs) have been reported to improve survival in rats with hemorrhagic shock (HS). However, no consensus exists on the most effective HDACIs and their administration routes. We herein aimed to determine the optimal HDACIs and administration route in rats with HS. Methods: Survival analysis: In experiment I, male Sprague-Dawley rats were subjected to HS (mean arterial pressure [MAP] was maintained at 30-40 mm Hg for 20 min), and intravenously injected with the following agents (n = 8 per group): (1) no treatment, (2) vehicle (VEH), (3) entinostat (MS-275), (4) [ N -((6-(Hydroxyamino)-6-oxohexyl)oxy)-3,5-dimethylbenzamide] (LMK-235), (5) tubastatin A, (6) trichostatin A (TSA), and (7) sirtinol. In experiment II, rats were intraperitoneally injected with TSA. Mechanism research: In experiments I and II, rats were observed for 3 h, after which blood samples and liver, heart, and lung tissues were harvested. Results: In experiment I, 75% rats in the VEH group but only 25% rats in the LMK-235 and sirtinol groups died within ≤5 h of treatment, whereas the survival of rats in the MS-275, tubastatin A, and TSA groups was significantly prolonged. MS-275, LMK-235, tubastatin A, and TSA significantly reduced histopathological scores, apoptosis cell numbers, and inflammatory cytokine levels. In experiment II, the survival was longer after i.v. TSA treatment than after i.p. TSA treatment, and the IL-6 levels in the heart were significantly lower in rat who received i.p. TSA treatment than in those who received i.v. TSA treatment. Conclusions: The i.v. effect was superior to the i.p. effect, while nonselective and isoform-specific classes I and IIb HDACIs had similar effects.

Neurochemical properties for defining subdivisions of the mouse medial geniculate body.

The medial geniculate body (MGB) exhibits anatomical and physiological properties that underlie its role in the auditory system. Anatomical properties, including myelo- and cyto-architecture, are used to identify MGB subdivisions. Recently, neurochemical properties, including calcium-binding proteins, have also been employed to define the MGB subdivisions. Because these properties do not show clear boundaries in the MGB and do not involve anatomical connectivity, whether the MGB subdivisions can be defined based on anatomical and neurochemical properties remains unclear. In this study, 11 different neurochemical markers were employed for defining the MGB subdivisions. In terms of anatomical connectivity, immunoreactivities for vesicular transporter demonstrated glutamatergic, GABAergic and glycinergic afferents and provided clues about the boundaries of the MGB subdivisions. On the other hand, the distribution of novel neurochemical markers of the MGB demonstrated distinct boundaries of the MGB subdivisions and resulted in the discovery of a putative homolog of the rabbit internal division of the MGB. Additionally, corticotropin-releasing factor was expressed in the larger neurons in the medial division of the MGB (MGm), particularly in the caudal MGm. Lastly, the analysis of anatomical details by measuring the size and density of vesicular transporters revealed heterogeneity among the MGB subdivisions. Our results demonstrate that the MGB is composed of five subdivisions based on their anatomical and neurochemical properties.