Acyl-CoA binding protein for the experimental treatment of anorexia.

Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.

Dynamic degree centrality in stroke-induced Broca's aphasia varies based on first language: A functional MRI study.

BACKGROUND AND PURPOSE: This study sought to explore dynamic degree centrality (DC) variability in particular regions of the brain in patients with poststroke Broca aphasia (BA) using a resting-state functional magnetic resonance imaging (rs-fMRI) approach, comparing differences between Uyghur and Chinese BA patients. METHODS: This study investigated two factors, language and BA status, and divided patients into four groups: Uyghur aphasia patients (UA), Uyghur normal control subjects (UN), Chinese aphasia patients (CA), and Chinese normal subjects (CN) who underwent rs-fMRI analysis. Two-way analysis of variance (ANOVA) was used to calculate the comprehensive differences in dynamic DC among these four groups. Correlations between DC and language behavior were assessed with partial correlation analyses. RESULTS: Two-way ANOVA revealed comparable results for the results of pairwise comparisons of dynamic DC variability among the four groups in the right middle frontal gyrus/orbital part (ORBmid.R), right superior frontal gyrus/dorsolateral, and right precuneus (PCUN.R), with results as follows: UA < UN, CA > CN, UA < CA, and UN > CN (p < .05, with the exception of the p-values for UA and UN in superior frontal gyrus/dorsolateral). In contrast, the opposite results were observed for the right calcarine fissure and surrounding cortex (CAL.R, p < .05). CONCLUSION: The observed enhancement of dynamic DC variability in ORBmid.R and PCUN.R among Chinese BA patients and in CAL.R in Uyghur BA patients may be attributable to language network restructuring. Overall, these results suggest that BA patients who use different language families may exhibit differences in the network mechanisms that characterize observed impairments of language function.

Recent Research Progress on the Use of Transcranial Magnetic Stimulation in the Treatment of Vascular Cognitive Impairment.

Vascular Cognitive Impairment (VCI) is a condition where problems with brain blood vessels lead to a decline in cognitive abilities, commonly affecting the elderly and placing a significant burden on both patients and their families. Compared to medication and surgery, Transcranial Magnetic Stimulation (TMS) is a non-invasive treatment option with fewer risks and side effects, making it particularly suitable for elderly patients. TMS not only assesses the excitability and plasticity of the cerebral cortex, but its effectiveness in treating Vascular Cognitive Impairment (VCI) and its subtypes has also been validated in numerous clinical trials worldwide. However, there is still a lack of review on the physiological mechanisms of TMS treatment for VCI and its specific clinical application parameters. Therefore, this article initially provided a brief overview of the risk factors, pathological mechanisms, and classification of VCI. Next, the article explained the potential physiological mechanisms of TMS in treating VCI, particularly its role in promoting synaptic plasticity, regulating neurotransmitter balance, and improving the function of the default mode network. Additionally, The article also summarizes the application of rTMS in treating VCI and its subtypes, VCI-related sleep disorders, and the use of TMS in follow-up studies of VCI patients, providing empirical evidence for the clinical application of TMS and rTMS technologies.

Value of 2D ultrasonography in the diagnosis and evaluation of intrauterine adhesions - a prospective study.

RESEARCH QUESTION: What is the value of 2D ultrasonography in the diagnosis and assessment of intrauterine adhesions (IUA)? DESIGN: This was a prospective study conducted at a hysteroscopy centre. RESULTS: Of a total of 600 subjects recruited, 41 dropped out and 559 were finally enrolled and analysed. The observed 2D ultrasonography features, in decreasing order of frequency, were 'irregular endometrium' (37.9%), 'broken endometrial echo' (23.4%), 'thin endometrium' (13.7%), 'loss of endometrial echo' (13.1%,), 'hyperechoic focus' (12.5%) and 'fluid in the cavity' (8.8%). The sensitivity of individual ultrasound features ranged from 8.8% to 37.9%, whereas the specificity of individual ultrasound features ranged from 78.9% to 100%. When all the six ultrasound features were considered together, the sensitivity and specificity were 71.7% and 66.2% respectively. The sensitivity, specificity and accuracy of ultrasound diagnosis in the mid-proliferative phase, peri-ovulatory phase and mid-luteal phase did not appear to be significantly different statistically, although the results in the mid-proliferative phase appeared to be consistently higher than those in the mid-luteal phase. In women confirmed to have IUA, the likelihood of the adhesions being severe in nature in the presence of zero, one, two or three or more ultrasound features was 8.7%, 23.0%, 40.2% and 80.5%, respectively (P < 0.001). CONCLUSIONS: The findings in this study support the notions that ultrasonography examination in women suspected to have IUA cannot replace hysteroscopy in the diagnosis of the condition. However, it does provide useful clinical information regarding severity and could help in the planning of hysteroscopy to optimize management.

Inhibition of acyl-CoA binding protein (ACBP) by means of a GABAARγ2-derived peptide.

Acyl-CoA binding protein (ACBP) encoded by diazepam binding inhibitor (DBI) is an extracellular inhibitor of autophagy acting on the gamma-aminobutyric acid A receptor (GABAAR) γ2 subunit (GABAARγ2). Here, we show that lipoanabolic diets cause an upregulation of GABAARγ2 protein in liver hepatocytes but not in other major organs. ACBP/DBI inhibition by systemically injected antibodies has been demonstrated to mediate anorexigenic and organ-protective, autophagy-dependent effects. Here, we set out to develop a new strategy for developing ACBP/DBI antagonists. For this, we built a molecular model of the interaction of ACBP/DBI with peptides derived from GABAARγ2. We then validated the interaction between recombinant and native ACBP/DBI protein and a GABAARγ2-derived eicosapeptide (but not its F77I mutant) by pull down experiments or surface plasmon resonance. The GABAARγ2-derived eicosapeptide inhibited the metabolic activation of hepatocytes by recombinant ACBP/DBI protein in vitro. Moreover, the GABAARγ2-derived eicosapeptide (but not its F77I-mutated control) blocked appetite stimulation by recombinant ACBP/DBI in vivo, induced autophagy in the liver, and protected mice against the hepatotoxin concanavalin A. We conclude that peptidomimetics disrupting the interaction between ACBP/DBI and GABAARγ2 might be used as ACBP/DBI antagonists. This strategy might lead to the future development of clinically relevant small molecules of the ACBP/DBI system.

Efficacy and safety evaluation of Ginkgo biloba dropping pill (GBDP) on stable angina pectoris complicated with depression: A placebo-controlled, randomized, double-blind, multicenter study.

BACKGROUND: Stable angina pectoris (SAP) is a clinical condition characterized by reversible and temporary myocardial ischemia and hypoxia. A majority of SAP patients also experience depressive disorders, which adversely affect their disease prognosis and overall quality of life. However, the clinical utility of existing antidepressants is constrained by their side effects. Ginkgo biloba dropping pill (GBDP), a Chinese patented medication, has demonstrated efficacy in the treatment of both coronary heart disease and mental disorders. This prospective, randomized, double-blind, multicenter clinical trial aimed to assess the effectiveness and safety of GBDP as an adjuvant therapy for SAP complicated by depression. METHODS: Participants were randomly assigned in a 1:1 ratio to receive either GBDP or a placebo (5 pills, three times a day) in addition to standard therapy for a duration of 12 weeks. The Seattle Angina Questionnaire (SAQ) was administered every 4 weeks during the treatment, and angina event frequency was assessed weekly. The 36-item Short-Form (SF-36) and Hamilton Depression Scale (HAMD) scores were measured both before and after the treatment. RESULTS: Out of the 72 patients, 68 (n = 34 per group) completed the entire study. At the first visit (4 weeks ± 3 days), the SAQ-Angina Stability score in the GBDP group was significantly higher than that in the placebo group (p < 0.05). While the average weekly frequency of angina episodes in the placebo group notably increased after 12 weeks of treatment (p < 0.05), it displayed an improving trend in the GBDP group (p > 0.05). By the endpoint, each subcategory score of SF-36 in the GBDP group exhibited significant improvement compared to baseline (p < 0.05). The comparison of score improvement between the two groups revealed that the SF-PCS score of the GBDP group was higher than that of the placebo group (p < 0.05). HAMD scores in both groups significantly increased after treatment (p < 0.05). No discernible difference in the incidence of adverse reactions was observed between the two groups (p > 0.05). CONCLUSION: In patients with SAP complicated by depression, GBDP, when combined with standard treatment, rapidly and safely alleviates angina pectoris symptoms. It demonstrates therapeutic potential in enhancing the quality of life and alleviating depressive symptoms.

Orthotopic Model of Hepatocellular Carcinoma in Mice.

Orthotopic models of hepatocellular carcinoma (HCC) consist in the implantation of tumor cells into the liver by direct intrahepatic injection. In this model, tumorigenesis is triggered within the hepatic microenvironment, thus mimicking the metastatic behavior of HCC. Herein, we detail a surgically mediated methodology that allows the reproducible and effective induction of liver-sessile tumors in mice. We enumerate the steps to be followed before and after the surgical procedure, including HCC cell preparation, the quantity of cancer cells to be injected, presurgical preparation of the mice, and finally, postoperative care. The surgical procedure involves laparotomy to expose the liver, injection of cells into the left-lateral hepatic lobe, and closure of the incision with sutures followed by wound clips. We also provide information concerning the subsequent tumor growth follow-up, as well as the application of bioluminescence imaging to monitor tumor development.

A Mouse Model of Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma Induced by Western Diet and Carbon Tetrachloride.

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD). Obesity is a known risk factor of NASH, which, in turn, increases the risk of developing cirrhosis (liver scarring) and hepatocellular carcinoma (HCC). In addition to being a potentially life-threatening condition, public health concerns surrounding NASH are amplified by the lack of FDA-approved treatments. Although various preclinical models reflecting both the histopathology and the pathophysiological progression of human NASH exist, most of these models are diet-based and require 6-13 months for NASH symptom manifestation. Here, we describe a simple and rapid-progression model of NASH and NASH-driven HCC in mice. Mice received a western diet equivalent (WD; i.e., a high-fat, high-fructose, and high-cholesterol diet), high-sugar water (23.1 g/L fructose and 18.9 g/L glucose), and weekly intraperitoneal injections of carbon tetrachloride (CCl4) at a dose of 0.2 µL/g of body weight. The resulting phenotype, consisting in liver fibrosis and HCC, appeared within 24 weeks of diet/treatment initiation and presented similar histological and transcriptomic features as human NASH and NASH-driven HCC, thereby supporting the adequacy of this preclinical model for the development and evaluation of drugs that can prevent or reverse these diseases.

A Mouse Model of Hepatocellular Carcinoma Induced by Streptozotocin and High-Fat Diet.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the second most common cause of cancer-related death. HCC is associated to chronic diseases such as viral hepatitis, alcoholic, and non-alcoholic fatty liver disease (NAFLD), diabetes mellitus, and obesity, among others. Although pre-clinical models have been investigated to mimic the transition from NAFLD to HCC, they do not accurately reproduce the phenotypic evolution from simple steatosis to steatohepatitis, fibrosis/cirrhosis, and HCC. Hence, these models have failed to demonstrate the influence of diabetes on hepatic carcinogenesis. Here, we report a novel mouse model of HCC triggered by fast-developing diabetes and NAFLD. The first step consists in a single intraperitoneal injection of a low dose of streptozotocin into neonatal C57BL/6J mice to induce type 2 diabetes. In a second step, mice are fed with high-fat diet to accelerate the development of simple steatosis. Continuous high-fat diet exacerbates hepatic fat deposition with increased lobular inflammation (by activation of foam cell-like macrophages) and fibrosis (by activating hepatic stellate cells), two representative pathological traits of steatohepatitis/fibrosis. After 20 weeks, all mice developed multiple HCCs. This model of hepatic carcinogenesis triggered by diabetes mellitus and NAFLD offers the advantage of being rapid and accurately recapitulates the pathogenesis of human HCC without the need of administering hepatic carcinogens.

Targeted Analysis of Glycerophospholipids and Mono-, Di-, or Tri-Acylglycerides in Liver Cancer.

The metabolic rearrangements of hepatic metabolism associated with liver cancer are still incompletely understood. There is an ongoing need to identify novel and more efficient diagnostic biomarkers and therapeutic targets based on the metabolic mechanisms of these diseases. In comparison to traditional diagnostic biomarkers, metabolomics is a comprehensive technique for discovering chemical signatures for liver cancer screening, prediction, and earlier diagnosis. Lipids are a large and diverse group of complex biomolecules that are at the heart of liver physiology and play an important role in the development and progression of cancer. In this chapter, we described two detailed protocols for targeted lipids analysis: glycerophospholipids and mono, di, tri-acylglycerides, both by Flow Injection Analysis (FIA) HPLC coupled to a SelexIon/QTRAP 6500+ system. These approaches provide a targeted lipidomic metabolomic signature of dissimilar metabolic disorders affecting liver cancers.

Isolation of Primary Mouse Hepatocytes and Non-Parenchymal Cells from a Liver with Precancerous Lesions.

In the early stages of liver carcinogenesis, rare hepatocytes and cholangiocytes are transformed into preneoplastic cells, which can progressively acquire a neoplastic phenotype, favored by the failure of natural antitumor immunosurveillance. The detailed study of both hepatic parenchymal (e.g., hepatocytes) and non-parenchymal cells (NPCs), such as immune cells, could help understand the cellular microenvironment surrounding these pre-cancerous and neoplastic lesions.Cultures of primary hepatocytes are of interest in various biomedical research disciplines, serving as an ex vivo model for liver physiology. Obtaining high viability and yield of primary mouse hepatocytes and other liver cell populations is technically challenging, thus limiting their use. In the first section of the current chapter, we introduce a protocol based on the two-step collagenase perfusion technique (by inferior vena cava) to isolate hepatocytes and, to a lower extent, NPCs and detailed the different considerations to take into account for a successful perfusion. The liver is washed by perfusion, hepatocytes are dissociated with collagenase, and different cell populations are separated by centrifugation. Various techniques have been described for the isolation of healthy and malignant hepatocytes; however, the viability and purity of the isolated cells is frequently not satisfactory. Here, we significantly optimized this protocol to reach improved yield and viability of the hepatocytes and concomitantly obtain preserved NPC populations of the liver.Within NPCs, tissue-resident or recruited immune cells are essential actors regulating hepatocarcinogenesis. However, simultaneous isolation of hepatic leukocytes together with other cell types generally yields low immune cell numbers hindering downstream application with these cells. In the second section of this chapter, as opposed to the first section primarily aiming to isolate hepatocytes, we present a tissue dissociation protocol adapted to efficiently recover leukocytes from non-perfused bulk (pre-)cancerous livers. This protocol has been optimized to be operator-friendly and fast compared to other liver processing methods, allowing easy simultaneous sample processing to retrieve hepatic (tumor-infiltrating) immune cells.

Biomarker Identification in Liver Cancers Using Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) Imaging: An Approach for Spatially Resolved Metabolomics.

Liver cancers are characterized by interindividual and intratumoral heterogeneity, which makes early diagnosis and the development of therapies challenging. Desorption electrospray ionization mass spectrometry (DESI-MS) imaging is a potent and sensitive MS ionization technique for direct, unaltered 2D and 3D imaging of metabolites in complex biological samples. Indeed, DESI gently desorbs and ionizes analyte molecules from the sample surface using an electrospray source of highly charged aqueous spray droplets in ambient conditions. DESI-MS imaging of biological samples allows untargeted analysis and characterization of metabolites in liver cancers to identify new biomarkers of malignancy. In this chapter, we described a detailed protocol using liver cancer samples collected and stored for histopathology examination, either as frozen or as formalin-fixed, paraffin-embedded specimens. Such hepatocellular carcinoma samples can be subjected to DESI-MS analyses, illustrating the capacity of spatially resolved metabolomics to distinguish malignant lesions from adjacent normal liver tissue.

Stiffness and BMP-2 Mimetic Peptide Jointly Regulate the Osteogenic Differentiation of Rat Bone Marrow Stromal Cells in a Gelatin Cryogel.

Both biochemical and mechanical cues could regulate the function of stem cells, but the interaction mechanism of their signaling pathway remains unclear, especially in the three-dimensional (3D) culture mode. Higher matrix stiffness promotes osteogenic differentiation of stem cells, and bone morphogenic protein-2 (BMP-2) has been clinically applied to promote bone regeneration. Here, the crosstalk of extracellular mechanical signals on BMP-2 signaling was investigated in rat bone marrow stromal cells (rMSCs) cultured inside cryogels with interconnective pores. Stiff cryogel independently promoted osteogenic differentiation and enhanced the autocrine secretion of BMP-2, thus stimulating increased phosphorylation levels of the Smad1/5/8 complex. BMP-2 mimetic peptide (BMMP) and high cryogel stiffness jointly guided the osteogenic differentiation of rMSCs. Inhibition of rho-associated kinase (ROCK) by Y-27632 or inhibition of nonmuscle myosin II (NM II) by blebbistatin showed that osteogenesis induction by BMP-2 signaling, as well as autocrine secretion of BMP-2 and phosphorylation of the Smad complex, requires the involvement of cytoskeletal tension and ROCK pathway signaling. An interconnective microporous cryogel scaffold promoted rMSC osteogenic differentiation by combining matrix stiffness and BMMP, and it accelerated critical cranial defect repair in the rat model.

Evaluation of combination of ALA-PDT and interferon for cervical low-grade squamous intraepithelial lesion (LSIL).

BACKGROUND: Cervical LSIL is a precancerous disease which requires regular follow-up. High risk patients need active interventions. Interferon and topical PDT have been used in the treatment of cervical LSIL. The aim of this study was to evaluate the combination use of topical PDT and interferon in the treatment of cervical LSIL. MATERIALS AND METHODS: A prospective study was carried out involving 159 women with cervical LSIL and high risk human papillomaviruses (hr-HPV) infection. Patients were divided into three groups. Group 1-receiving interferon suppository only, Group 2-receiving 19 mg/cm2 ALA plus post PDT interferon, and Group 3-receiving 38 mg/cm2 ALA plus post PDT interferon. The primary endpoint was pathological regression. The secondary endpoints were the HPV negative conversion rate and the adverse effects of treatment. RESULTS: At 6-12 months after PDT, for Group 1, the effective rate, CR rate and HPV negative conversion rate was 48.3 %, 43.3 % and 24.0 %, respectively. For Group 2, the effective rate, CR rate and HPV negative conversion rate were 89.3 %, 71.4 %, and 72.4 %, respectively. For Group 3, the effective rate, CR rate and HPV negative conversion rate were 91.5 %, 66.1 %, and 64.4 %, respectively, significantly higher than those of interferon only group. Two ALA dose group study showed similar efficacy. No patient experienced serious adverse effects. CONCLUSIONS: ALA-PDT combined with interferon therapy was feasible and tolerable. Two ALA dose groups showed similar outcomes in treating cervical LSIL.

A novel configuration for the fixation of intra-articular C2.3 distal humerus fractures with the potential for minimally invasive surgery: a biomechanical evaluation and finite element analysis.

BACKGROUND: Distal humerus fractures are a challenge to treat, and the current standard of care, open reduction internal fixation with a double-plate, has a high rate of complications. We proposed a novel internal fixation configuration, lateral intramedullary nail and medial plate (LINMP) and verified its rigidity through biomechanical tests and finite element analysis. METHODS: The study involved biomechanical testing of 30 synthetic humerus models to compare 2 different fixation systems for an AO 13C-2.3 type fracture. The orthogonal double-plate (ODP) group and the LINMP group were compared through biomechanical testing to measure stiffness and failure load fewer than 3 working conditions. Based on the results, we optimized the intramedullary nail by eliminating the holes at the distal end of the nail and incorporating a 2-hole external locking plate. The Finite element analysis was also conducted to further compare the modified LINMP configuration with the previous 2 fixation configurations. RESULTS: In biomechanical tests, the ODP group exhibited lower stiffness under bending and compression forces compared to the LINMP group, but higher stiffness and failure loads under torsion force. In finite element analysis, the modified LINMP reduces the maximum stress of the fixation structure without significantly reducing the stiffness under bending stress and axial compression conditions. In torsion stress conditions, the modified LINMP enhances both the maximum stress and the stiffness, although it remains marginally inferior to the ODP structure. CONCLUSION: Our study demonstrates that the innovative LINMP presents comparable or slightly superior concerning bending and axial loading compared to orthogonal double-plate osteosynthesis for distal humeral intra-articular fractures, which might become a minimally invasive option for these fractures.

Pan-cancer characterization of ncRNA synergistic competition uncovers potential carcinogenic biomarkers.

Non-coding RNAs (ncRNAs) act as important modulators of gene expression and they have been confirmed to play critical roles in the physiology and development of malignant tumors. Understanding the synergism of multiple ncRNAs in competing endogenous RNA (ceRNA) regulation can provide important insights into the mechanisms of malignant tumors caused by ncRNA regulation. In this work, we present a framework, SCOM, for identifying ncRNA synergistic competition. We systematically construct the landscape of ncRNA synergistic competition across 31 malignant tumors, and reveal that malignant tumors tend to share hub ncRNAs rather than the ncRNA interactions involved in the synergistic competition. In addition, the synergistic competition ncRNAs (i.e. ncRNAs involved in the synergistic competition) are likely to be involved in drug resistance, contribute to distinguishing molecular subtypes of malignant tumors, and participate in immune regulation. Furthermore, SCOM can help to infer ncRNA synergistic competition across malignant tumors and uncover potential diagnostic and prognostic biomarkers of malignant tumors. Altogether, the SCOM framework (https://github.com/zhangjunpeng411/SCOM/) and the resulting web-based database SCOMdb (https://comblab.cn/SCOMdb/) serve as a useful resource for exploring ncRNA regulation and to accelerate the identification of carcinogenic biomarkers.

Association of carbohydrate intake from different sources with all-cause and cardiovascular mortality among chronic kidney disease populations: assessment of 1999-2018 National Health and Nutrition Examination Survey participation.

This study analysed the data from the NHANES (1999-2018) to examine how different sources of carbohydrate intake affected the all-cause and cardiovascular mortality of 11,302 chronic kidney disease (CKD) patients. The data were adjusted for other factors using various methods. The results showed that CKD patients (stages 1-2 and 3-5) who consumed more carbohydrates from whole grains, fruits, vegetables and less carbohydrates from fruit juice or sauces had lower mortality rates. Replacing fat intake with carbohydrates from whole grains (HR = 0.86[0.78-0.95]), fruits (raw) (HR = 0.79[0.70-0.88]) and non-starchy vegetables (HR = 0.82[0.70-0.96]), but not protein intake, was linked to lower all-cause mortality. The fibre content in carbohydrates might partly account for the benefits of selected carbohydrate intake. This study provided practical recommendations for optimising the carbohydrate sources in CKD patients.

Protein regulator of cytokinesis 1: a potential oncogenic driver.

Protein regulator of cytokinesis 1 (PRC1) is involved in cytokinesis. Growing evidence suggests the association of PRC1 with multiple cancers. Here, we unveil that, in 28 cancer types, PRC1 is higher expressed in tumor tissues than in non-malignant tissues. Overexpression of PRC1 indicates unfavorable prognostic value, especially in ACC, LGG, KIRP, LICH, LUAD, MESO, PAAD, SARC and UCEC, while methylation of the PRC1 gene at sites associated with its inactivation has a favorable prognostic value in ACC, KIRP, LUAD, MESO, KIRP and LGG. Differentially expressed genes (DEGs) associated with high (> median) PRC1 expression contribute to key signaling pathways related with cell cycle, DNA damage and repair, EMT, cell migration, invasion and cell proliferation in most cancer types. More specifically, the DEGs involved in RAS/RAF/MAPK, PI3K/AKT, WNT, NOTCH, TGF-ß, integrin, EMT process, focal adhesion, RHO GTPase-related pathway or microtubule cytoskeleton regulation are upregulated when PRC1 expression is above median, as confirmed for most cancers. Most importantly, high expression of PRC1 appears to be associated with an overabundance of poor-prognosis TH2 cells. Furthermore, positive correlations of PRC1 and some immune checkpoint genes (CD274, CTLA4, HAVCR2, LAG3, PDCD1, PDCD1LG2, TIGIT, and CD86) were observed in several cancers, especially BLCA, BRCA, KIRC, LUAD, LIHC, PRAD and THCA. These findings plead in favor of further studies validating the diagnostic and prognostic impact of PRC1 as well as the elaboration of pharmacological strategies for targeting PRC1.

Impact of inflammation and anti-inflammatory modalities on diabetic cardiomyopathy healing: From fundamental research to therapy.

Diabetic cardiomyopathy (DCM) is a prevalent cardiovascular complication of diabetes mellitus, characterized by high morbidity and mortality rates worldwide. However, treatment options for DCM remain limited. For decades, a substantial body of evidence has suggested that the inflammatory response plays a pivotal role in the development and progression of DCM. Notably, DCM is closely associated with alterations in inflammatory cells, exerting direct effects on major resident cells such as cardiomyocytes, vascular endothelial cells, and fibroblasts. These cellular changes subsequently contribute to the development of DCM. This article comprehensively analyzes cellular, animal, and human studies to summarize the latest insights into the impact of inflammation on DCM. Furthermore, the potential therapeutic effects of current anti-inflammatory drugs in the management of DCM are also taken into consideration. The ultimate goal of this work is to consolidate the existing literature on the inflammatory processes underlying DCM, providing clinicians with the necessary knowledge and tools to adopt a more efficient and evidence-based approach to managing this condition.

[Targeted muscle reinnervation: a surgical technique of human-machine interface for intelligent prosthesis].

Objective: To review targeted muscle reinnervation (TMR) surgery for the construction of intelligent prosthetic human-machine interface, thus providing a new clinical intervention paradigm for the functional reconstruction of residual limbs in amputees. Methods: Extensively consulted relevant literature domestically and abroad and systematically expounded the surgical requirements of intelligent prosthetics, TMR operation plan, target population, prognosis, as well as the development and future of TMR. Results: TMR facilitates intuitive control of intelligent prostheses in amputees by reconstructing the "brain-spinal cord-peripheral nerve-skeletal muscle" neurotransmission pathway and increasing the surface electromyographic signals required for pattern recognition. TMR surgery for different purposes is suitable for different target populations. Conclusion: TMR surgery has been certified abroad as a transformative technology for improving prosthetic manipulation, and is expected to become a new clinical paradigm for 2 million amputees in China.