Current Medical Science最新文献

Objective: The trigger receptor expressed on myeloid cells-2 (TREM2) pathway in myeloid cells is a key disease-inducing immune signaling hub that is essential for detecting tissue damage and limiting its pathological spread. However, the role and potential mechanisms of TREM2 in wound repair remain unclear. The purpose of this study was to determine the role and mechanism of TREM2 in skin wound healing in mice.

Methods: Immunofluorescence staining was used to determine the expression and cellular localization of TREM2 and test the effects of TREM2 knockout on angiogenesis, glycolysis, and lactylation in skin tissue. Western blotting was used to analyze the expression of the Akt/mTOR/HIF-1α signaling pathway in the wounded skin tissues of wild-type (WT) and TREM2 knockout mice. A coimmunoprecipitation assay was used to determine whether HIF-1α, which mediates angiogenesis, is modified by lactylation.

Results: The number of TREM2⁺ macrophages was increased, and TREM2⁺ macrophages mediated angiogenesis after skin injury. TREM2 promoted glycolysis and lactylation in macrophages during wound healing. Mechanistically, TREM2 promoted macrophage glycolysis and angiogenesis in wounded skin tissues by activating the Akt/mTOR/HIF-1α signaling pathway. HIF-1α colocalized with Klac to mediate lactylation in macrophages, and lactate could stabilize the expression of the HIF-1α protein through lactylation. Lactate treatment ameliorated the impaired angiogenesis and delayed wound healing in wounded skin in TREM2 knockout mice.

Conclusion: TREM2⁺ macrophage-mediated glycolysis can promote angiogenesis and wound healing. Our findings provide an effective strategy and target for promoting skin wound healing.

Objective: This study aimed to investigate the incidence and predictors of non-variceal upper gastrointestinal bleeding (NVUGIB) in hospitalized patients with coronavirus disease 2019 (COVID-19), as well as the inpatient outcomes associated with this complication.

Methods: This was an analysis of the National Inpatient Sample Database from January to December 2020. Adult COVID-19 patients were categorized into two groups based on NVUGIB development during hospitalization. Multivariate logistic analysis was performed to identify predictors and outcomes associated with NVUGIB in hospitalized COVID-19 patients in the US, after adjusting for age, sex, race, and Charlson Comorbidity Index (CCI) score, using Stata/BE 17.0.

Results: Among 1 050 045 hospitalized patients, 1.87% developed NVUGIB. Asian Americans had the highest risk, followed by Native Americans, Hispanics, and African Americans, with odds ratios (ORs) of 1.70, 1.59, 1.40, and 1.14, respectively. Patients with higher CCI scores were also at greater risk (with ORs of 1.47, 2.09, and 3.45 for CCI scores of 1, 2, and 3, respectively). COVID-19 patients with NVUGIB had a higher risk of inpatient mortality (OR=3.84), acute kidney injury (OR=3.12), hypovolemic shock (OR=13.7), blood transfusion (OR=7.02), and in-hospital cardiac arrest (OR=4.02).

Conclusion: NVUGIB occurred in 1.87% of hospitalized COVID-19 patients and was associated with a threefold increase in mortality. Further research is necessary to identify strategies for reducing its incidence in COVID-19 patients with multiple risk factors.

Objective: This prospective randomized controlled study was conducted to evaluate the safety and efficacy of the Pringle hepatic hilar occlusion with a bulldog clamp in laparoscopic liver resection.

Methods: From March 1, 2020 to July 31, 2021, 80 patients were enrolled, including 40 undergoing intraperitoneal Pringle maneuver (IPM) and 40 extraperitoneal Pringle maneuver (EPM). The observation indices included basic preoperative clinical characteristics and intraoperative and postoperative liver function indices.

Results: There were no significant differences in the basic characteristics or types of hepatectomy, intraoperative blood loss, intraoperative blood transfusion, or hepatectomy time between the IPM and EPM groups. However, the blocking and operation time in the IPM group was shorter than that in the EPM group. There were no significant differences in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels on the first day after surgery or in total bilirubin (TBIL) or albumin (ALB) levels on the first, third, or fifth days after surgery. However, C-reactive protein (CRP) levels on the first and third days, ALT and AST levels on the third and fifth days were lower, and hospital stay after surgery was shorter in the IPM group than in the EPM group.

Conclusion: IPM using bulldog clamps is simple, safe, and effective. The inflammatory reaction is less severe, the degree of liver function injury is lower, and recovery is faster.

Objective: Chronic kidney disease (CKD) is a complex disorder resulting from a combination of various environmental and genetic factors. Considerable efforts have been dedicated to elucidating its etiological mechanisms. Nevertheless, the pathogenic mechanism of CKD remains poorly understood, which hinders the development of effective therapeutic strategies. In this study, we aimed to identify novel mediators that could contribute to the development of CKD.

Methods: The ClinVar, STRING, MEME Suite, TRRUST, bedtools, GEO, and R Studio databases and software were used to analyze their common features and investigate potential CKD disease genes. Transcriptomic analysis, immunohistochemistry, qRT-PCR, and Western blotting were utilized to further validate the role of ECT2 in kidney fibrosis.

Results: In total, 26 CKD disease genes were obtained from the ClinVar database, and the STRING, MEME Suite, TRRUST, bedtools, and GEO databases and software were used to analyze their common properties and explore potential CKD disease genes. Epithelial cell transforming sequence 2 (ECT2), cyclin B 1, caspase 7 and collagen alpha-1 (IV) were identified as potential candidates for CKD progression. Weighted correlation network analysis (WGCNA) subsequently revealed the relationships between potential genes and CKD. The results of the transcriptomic analysis further confirmed that ECT2 expression was greater in the kidney tissue of CKD patients than in that of healthy controls. Next, immunohistochemistry and Western blotting demonstrated that ECT2 was predominantly expressed in the renal tubules of a unilateral ureteral obstruction (UUO) mouse model. Consistently, in vitro experiments revealed that ECT2 was upregulated in TGF-β1-treated HK-2 cells. Moreover, ECT2 overexpression or knockdown in HK-2 cells altered the intensity of fibrosis markers.

Conclusion: ECT2 significantly affects the development and progression of CKD, particularly in association with tubulointerstitial fibrosis.

Objective: To evaluate the accuracy and parsing ability of GPT 4.0 for Japanese medical practitioner qualification examinations in a multidimensional way to investigate its response accuracy and comprehensiveness to medical knowledge.

Methods: We evaluated the performance of the GPT 4.0 on Japanese Medical Licensing Examination (JMLE) questions (2021-2023). Questions are categorized by difficulty and type, with distinctions between general and clinical parts, as well as between single-choice (MCQ1) and multiple-choice (MCQ2) questions. Difficulty levels were determined on the basis of correct rates provided by the JMLE Preparatory School. The accuracy and quality of the GPT 4.0 responses were analyzed via an improved Global Qualily Scale (GQS) scores, considering both the chosen options and the accompanying analysis. Descriptive statistics and Pearson Chi-square tests were used to examine performance across exam years, question difficulty, type, and choice. GPT 4.0 ability was evaluated via the GQS, with comparisons made via the Mann-Whitney U or Kruskal-Wallis test.

Results: The correct response rate and parsing ability of the GPT4.0 to the JMLE questions reached the qualification level (80.4%). In terms of the accuracy of the GPT4.0 response to the JMLE, we found significant differences in accuracy across both difficulty levels and option types. According to the GQS scores for the GPT 4.0 responses to all the JMLE questions, the performance of the questionnaire varied according to year and choice type.

Conclusion: GTP4.0 performs well in providing basic support in medical education and medical research, but it also needs to input a large amount of medical-related data to train its model and improve the accuracy of its medical knowledge output. Further integration of ChatGPT with the medical field could open new opportunities for medicine.

Objective: Human adipose-derived stem cells (ASCs) have shown considerable potential for tissue regeneration. FK506 binding protein (FKBP) 5 is a cochaperone of several proteins. The purpose of this work was to explore the function of FKBP5 in ASC osteogenesis.

Methods: Lentivirus infection was used to overexpress or knock down FKBP5 in ASCs. To inhibit FKBP5, SAFit2, a specific inhibitor of FKBP5, was used. Next, the osteogenic capacity of ASCs was evaluated via alkaline phosphatase (ALP) staining, and extracellular calcium precipitation was detected via Alizarin red S staining. The binding proteins of FKBP5 were assessed via proteomics and validated via coimmunoprecipitation experiments.

Results: Following osteogenic induction, FKBP5 expression increased at both the mRNA and protein levels. Interestingly, FKBP5 upregulation by lentivirus infection increased the ability of ASCs to differentiate into osteoblasts, as revealed by ALP staining, while ALP activity also increased. Moreover, increased extracellular calcium precipitation confirmed that FKBP5 overexpression promoted ASC osteogenesis into osteocytes. On the other hand, FKBP5 knockdown or functional suppression with SAFit2 decreased this process. Furthermore, the proteomics and coimmunoprecipitation data demonstrated that FKBP5 bound to a variety of proteins in ASCs. These proteins serve as the molecular chaperone base upon which the osteogenesis-regulating activity of FKBP5 rests.

Conclusion: Our study revealed that FKBP5 enhances the osteogenesis of ASCs, providing a feasible method for clinical bone tissue engineering applications.

The medical metaverse is a combination of medicine, computer science, information technology and other cutting-edge technologies. It redefines the method of information interaction about doctor-patient communication, medical education and research through the integration of medical data, knowledge and services in a virtual environment. Artificial intelligence (AI) is a discipline that uses computer technology to study and develop human intelligence. AI has infiltrated every aspect of medical metaverse and is deeply integrated with the technologies that build medical metaverse, such as large language models (LLMs), digital twins, blockchain and extended reality (including VR/AR/XR). AI has become an integral part of the medical metaverse building process. Moreover, AI also provides richer medical metaverse functions, including diagnosis, education, and consulting. This paper aims to introduce how AI supports the development of medical metaverse, including its specific application scenarios, shortcomings and future development. Our goal is to contribute to the advancement of more sophisticated and intelligent medical methods.

The brain-computer interface (BCI) system serves as a critical link between external output devices and the human brain. A monitored object's mental state, sensory cognition, and even higher cognition are reflected in its electroencephalography (EEG) signal. Nevertheless, unprocessed EEG signals are frequently contaminated with a variety of artifacts, rendering the analysis and elimination of impurities from the collected EEG data exceedingly challenging, not to mention the manual adjustment thereof. Over the last few decades, the rapid advancement of artificial intelligence (AI) technology has contributed to the development of BCI technology. Algorithms derived from AI and machine learning have significantly enhanced the ability to analyze and process EEG electrical signals, thereby expanding the range of potential interactions between the human brain and computers. As a result, the present BCI technology with the help of AI can assist physicians in gaining a more comprehensive understanding of their patients' physical and psychological status, thereby contributing to improvements in their health and quality of life.

There are several types of brain tumors but glioblastoma (GBM) is one of the highly malignant tumors. A primary concern with GBM is that the treatment is inadequate. Even after giving many multi-stacked combinations of therapies to patients, inclusive of chemotherapy, radiation, and surgery, the median survival rate remains poor. Due to its heterogeneous nature, the use of selective therapy for specific targeting of tumor cells is of particular importance. Although many treatment alternatives which include surgery with adjuvant chemotherapy and radiotherapy are available, the prognosis of the disease is very poor. Combination therapy is becoming the foundation of modern antitumor therapy and it is continuously evolving and developing innovative drug regimens as evidenced by ongoing preclinical and clinical trials. In this review, we discuss the current treatment options and emerging therapeutic approaches for the treatment of GBM. The prospects for alternative glioblastoma therapy are also discussed.

Cystic fibrosis (CF) is a hereditary disorder characterized by mutations in the CFTR gene, leading to impaired chloride ion transport and subsequent thickening of mucus in various organs, particularly the lungs. Despite significant progress in CF management, current treatments focus mainly on symptom relief and do not address the underlying genetic defects. Stem cell and gene therapies present promising avenues for tackling CF at its root cause. Stem cells, including embryonic, induced pluripotent, mesenchymal, hematopoietic, and lung progenitor cells, offer regenerative potential by differentiating into specialized cells and modulating immune responses. Similarly, gene therapy aims to correct CFTR gene mutations by delivering functional copies of the gene into affected cells. Various approaches, such as viral and nonviral vectors, gene editing with CRISPR-Cas9, small interfering RNA (siRNA) therapy, and mRNA therapy, are being explored to achieve gene correction. Despite their potential, challenges such as safety concerns, ethical considerations, delivery system optimization, and long-term efficacy remain. This review provides a comprehensive overview of the current understanding of CF pathophysiology, the rationale for exploring stem cell and gene therapies, the types of therapies available, their mechanisms of action, and the challenges and future directions in the field. By addressing these challenges, stem cell and gene therapies hold promise for transforming CF management and improving the quality of life of affected individuals.