ABSTRACT
Anxiety-related disorders respond to cognitive behavioral therapies, which involved the medial prefrontal cortex (mPFC). Previous studies have suggested that subregions of the mPFC have different and even opposite roles in regulating innate anxiety. However, the specific causal targets of their descending projections in modulating innate anxiety and stress-induced anxiety have yet to be fully elucidated. Here, we found that among the various downstream pathways of the prelimbic cortex (PL), a subregion of the mPFC, PL-mediodorsal thalamic nucleus (MD) projection, and PL-ventral tegmental area (VTA) projection exhibited antagonistic effects on anxiety-like behavior, while the PL-MD projection but not PL-VTA projection was necessary for the animal to guide anxiety-related behavior. In addition, MD-projecting PL neurons bidirectionally regulated remote but not recent fear memory retrieval. Notably, restraint stress induced high-anxiety state accompanied by strengthening the excitatory inputs onto MD-projecting PL neurons, and inhibiting PL-MD pathway rescued the stress-induced anxiety. Our findings reveal that the activity of PL-MD pathway may be an essential factor to maintain certain level of anxiety, and stress increased the excitability of this pathway, leading to inappropriate emotional expression, and suggests that targeting specific PL circuits may aid the development of therapies for the treatment of stress-related disorders.
Subject(s)
Anxiety , Neural Pathways , Prefrontal Cortex , Stress, Psychological , Animals , Anxiety/psychology , Anxiety/physiopathology , Male , Stress, Psychological/psychology , Stress, Psychological/physiopathology , Prefrontal Cortex/physiopathology , Neural Pathways/physiopathology , Neural Pathways/physiology , Mice , Fear/physiology , Fear/psychology , Mice, Inbred C57BL , Ventral Tegmental Area/physiopathology , Thalamus/physiopathology , Mediodorsal Thalamic Nucleus/physiology , Mediodorsal Thalamic Nucleus/physiopathologyABSTRACT
BACKGROUND: To further clarify the acne profile of Chinese adult women, we included 1,156,703 adult women. An artificial intelligence algorithm was used to analyze images taken by high-resolution mobile phones to further explore acne levels in Chinese adult women. METHOD: In this study, we assessed the severity of acne by evaluating patients' selfies through a smartphone application. Furthermore, we gathered basic user information through a questionnaire, including details such as age, gender, skin sensitivity, and dietary habits. RESULTS: This study showed a gradual decrease in acne severity from the age of 25 years. A trough was reached between the ages of 40 and 44, followed by a gradual increase in acne severity. In terms of skin problems and acne severity, we have found that oily skin, hypersensitive skin, frequent makeup application and unhealthy dietary habits can affect the severity of acne. For environment and acne severity, we observed that developed city levels, cold seasons and high altitude and strong radiation affect acne severity in adult women. For the results of the AI analyses, the severity of blackheads, pores, dark circles and skin roughness were positively associated with acne severity in adult women. CONCLUSIONS: AI analysis of high-res phone images in Chinese adult women reveals acne severity trends. Severity decreases after 25, hits a low at 40-44, then gradually rises. Skin type, sensitivity, makeup, diet, urbanization, seasons, altitude, and radiation impact acne. Blackheads, pores, dark circles, and skin roughness are linked to acne severity. These findings inform personalized skincare and public health strategies for adult women.
Subject(s)
Acne Vulgaris , Artificial Intelligence , Adult , Humans , Female , Acne Vulgaris/epidemiology , Acne Vulgaris/complications , Skin , China/epidemiologyABSTRACT
BACKGROUND: An increasing number of surgical and nonsurgical interventions are available in the field of female genital plastic surgery. The rate of female genital plastic surgery has increased by nearly 220 percent over the past 5 years. Despite several studies on the topic, no relevant bibliometric analysis has been conducted. METHODS: We searched the Web of Science Core Collection for articles related to female genital plastic surgery. CiteSpace 6.1.R2 (Drexel University, USA) and VOSviewer 1.6.10.0 (Leiden University, the Netherlands) were used, and national distribution, institutions, journals, authors, and key words were analyzed and calculated. RESULTS: From 2003 to 2022, 1299 papers in the field of female genital plastic surgery were retrieved. There were more articles produced in the United States, and there were also two institutions in the Netherlands that were highly productive. A wide and close relationship has been established between researchers and institutions conducting female genital plastic surgery. Professor Bouman MB published the most articles on female genital plastic surgery in the Journal of Sexual Medicine. Female genital plastic surgery dominated the top 10 references with the highest local citation score. There were four clusters of key words with the most citations, and the most recently trending key words were "vaginal agenesis," "transgender," and "congenital adrenal hyperplasia." CONCLUSIONS: The purpose of this article is to provide a summary of the current research status focusing on female genital plastic surgery. It is hoped that more efforts will be made to promote the development of female genital plastic surgery in the future.
Subject(s)
Bibliometrics , Surgery, Plastic , Humans , Female , Surgery, Plastic/statistics & numerical data , Surgery, Plastic/trends , Plastic Surgery Procedures/statistics & numerical data , Gynecologic Surgical Procedures/statistics & numerical data , Genitalia, Female/surgeryABSTRACT
Localised scleroderma predominantly affects the skin with an unknown aetiology. Despite its clinical importance, no comprehensive bibliometric analysis has been conducted to assess the existing research landscape and future prospects for localised scleroderma. The articles related to localised scleroderma were retrieved from the WoSCC database and analysed by VOSviewer 1.6.10.0 (Leiden University, Netherlands), CiteSpace 6.1.R1 (Dreiser University, USA), and HistCite 2.1 (New York, United States). 2049 research papers pertaining to localised scleroderma spanning the years from 1993 to 2022 were extracted from the WoSCC database. The United States exhibited the highest productivity with 644 papers, accounting for 31.43% of the total output, followed by Germany with 206 papers (10.05%) and Italy with 200 papers (9.76%). Regarding academic institutions and journals, the University of Texas System and Dermatology published the most significant number of papers, and Professor Ihn, H emerged as the most prolific contributor among scholars. The top 10 cited references primarily concentrated on the diagnosis and treatment of localised scleroderma. "Phototherapy" and "methotrexate (MTX)" surfaced as the most recent and noteworthy keywords, representing the research hotspots in the domain of localised scleroderma. This bibliometric analysis furnishes valuable insights into the contemporary research landscape of localised scleroderma.
Subject(s)
Scleroderma, Localized , Humans , Scleroderma, Localized/therapy , Skin , Bibliometrics , Databases, Factual , GermanyABSTRACT
EphB6 belongs to the receptor tyrosine kinase, whose low expression is associated with shorter survival of colorectal cancer (CRC) patients. But the role and mechanism of EphB6 in the progression of CRC need further study. In addition, EphB6 was mainly expressed in intestinal neurons. But how EphB6 is involved in functions of intestinal neurons has not been known. In our study, we constructed a mouse xenograft model of CRC by injecting CMT93 cells into the rectum of EphB6-deficient mice. We found that the deletion of EphB6 in mice promoted tumor growth of CMT93 cells in a xenograft model of CRC, which was independent of changes in the gut microbiota. Interestingly, inhibition of intestinal neurons by injecting botulinum toxin A into rectum of EphB6-deficient mice could eliminate the promotive effect of EphB6 deficiency on tumor growth in the xenograft model of CRC. Mechanically, the deletion of EphB6 in mice promoted the tumor growth in CRC by increasing GABA in the tumor microenvironment. Furthermore, EphB6 deficiency in mice increased the expression of synaptosomal-associated protein 25 in the intestinal myenteric plexus, which mediated the release of GABA. Our study concluded that EphB6 knockout in mice promotes tumor growth of CMT93 cells in a xenograft model of CRC by modulating GABA release. Our study found a new regulating mechanism of EphB6 on the tumor progression in CRC that is dependent on intestinal neurons.
Subject(s)
Cell Communication , Colorectal Neoplasms , Humans , Animals , Mice , Colorectal Neoplasms/metabolism , Intestines/pathology , Neurons/metabolism , Neurons/pathology , gamma-Aminobutyric Acid , Tumor MicroenvironmentABSTRACT
BACKGROUND: To better compare the progression of dark circles and the aging process in Chinese skin. A total of 100 589 Chinese males and 1 838 997 Chinese females aged 18 to 85, without facial skin conditions, and who had access to a smartphone with a high-resolution camera all took selfies. METHOD: Using a smartphone application with a built-in artificial intelligence algorithm, facial skin diagnostic evaluated the selfies and score the severity of the dark circles with four other facial indicators (including skin type, Pores, Acne vulgaris, and Blackheads). Basic information was collected with online questionnaire, including their age, gender, skin sensitivity, and dietary habits. RESULTS: In users between the age of 18 and 59, the prevalence of comprehensive, pigmented, and structural type of dark circles all rose with age. However, between the age of 60 and 85, the intensity of all types of dark circles diminished. Besides, vascular dark circles progressively worsen from the age of 18 to their peak at 39, and then gradually decline with age. Females typically have more pronounced black circles under their eyes than males in China. Bad eating habits, urbanization, regular cosmetics use, and sensitive skin positively correlate with severe dark circles. Vascular, comprehensive dark circles were worse in spring. Both pigmented and structural dark circles were worse in the summer. The results indicated that the intensity of dark circles was influenced by oily skin, wide pores, severe blackheads, and severe acne. CONCLUSIONS: Chinese men and women differed noticeably in the prevalence of each face aging indicator and the appearance of aging dark circles. Selfies could be automatically graded and examined by artificial intelligence, which is a quick and private method for quantifying signs of facial aging and identifying major problems for different populations. Artificial intelligence would assist in the development of individualized preventive and therapeutic interventions.
Subject(s)
Artificial Intelligence , Face , Skin Aging , Female , Humans , Male , Acne Vulgaris , East Asian People , Skin , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and overABSTRACT
BACKGROUND: Fat grafting is one of the most effective treatments for soft tissue restoration and augmentation. Adipose-derived stem cells (ASCs) supplementation is one of the foremost concerns to improve its efficiency. There have been several studies aiming at adipose-derived mesenchymal stem cells in fat grafting, but no relevant bibliometric research has conducted. METHODS: Articles about fat grafting and ASCs were retrieved in Web of Science Core Collection (WoSCC). Using VOSviewer 1.6.10.0 (Leiden University, the Netherlands) and CiteSpace 6.1.R2 (Drexel University, USA), the information of national distribution, institutions, journals, authors and keywords were evaluated and calculated. RESULTS: A total of 1166 papers in the field of ASCs in fat grafting were retrieved from 2002 to 2021. The USA produced the most articles, and the top 2 productive institutions were all from the USA. Researchers and institutions conducting ASCs in fat grafting research have shown a widespread and close connection. Plastic and Reconstructive Surgery published the most article on ASCs in fat grafting, and professor Rubin Peter is the most productive author. The top 10 references with the highest LCS mainly focused on applying ASCs to assist fat transplantation in plastic surgery. The most cited keywords formed 4 clusters, and "mesenchymal stem," "mesenchymal stromal cell," "stromal vascular fraction" and "long term" were the most recently trending keywords. CONCLUSIONS: This article provides a summary of the current research status focusing on fat grafting and ASCs. More efforts will be made to promote the application of ASCs in fat grafting. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Subject(s)
Adipocytes , Plastic Surgery Procedures , Humans , Adipocytes/transplantation , Bibliometrics , Adipose Tissue/transplantation , Stem CellsABSTRACT
Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is a subtype of the NOX family, which is mainly expressed in the pulmonary vasculature and pulmonary endothelial cells in the respiratory system. NOX4 has unique characteristics, and is a constitutively active enzyme that primarily produces hydrogen peroxide. The signaling pathways associated with NOX4 are complicated. Negative and positive feedback play significant roles in regulating NOX4 expression. The role of NOX4 is controversial because NOX4 plays a protective or damaging role in different respiratory diseases. This review summarizes the structure, enzymatic properties, regulation, and signaling pathways of NOX4. This review then introduces the roles of NOX4 in different diseases in the respiratory system, such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis.
Subject(s)
Lung Diseases/enzymology , NADPH Oxidase 4/metabolism , Animals , Humans , Lung Diseases/pathology , Models, Biological , Signal TransductionABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) and chronic inflammation with limited therapeutic options. Psoralen, a major active component extracted from Psoralea corylifolia L. seed, has several biological effects. However, the role of psoralen in IPF is still unclear. Here, we hypothesized that psoralen played an essential role in IPF in the inhibition of fibroblast proliferation and inflammatory response. A murine model of IPF was established by injecting bleomycin (BLM) intratracheally, and psoralen was administered for 14 days from the 7th to 21st day after BLM injection. Our results demonstrated that psoralen treatment reduced body weight loss and improved the survival rate of mice with IPF. Histological and immunofluorescent examination showed that psoralen alleviated BLM-induced lung parenchymal inflammatory and fibrotic alteration. Furthermore, psoralen inhibited proliferation and collagen synthesis of mouse fibroblasts and partially reversed BLM-induced expression of α-smooth muscle actin at both the tissue and cell level. Moreover, psoralen decreased the expression of transforming growth factor-ß1, interleukin-1ß, and tumor necrosis factor-α in the lungs of BLM-stimulated mice. Our results reveale for the first time that psoralen exerts therapeutic effects against IPF in a BLM-induced murine model.
ABSTRACT
Human single-strand (ss) DNA binding proteins 1 (hSSB1) has been shown to participate in DNA damage response and maintenance of genome stability by regulating the initiation of ATM-dependent signaling. ATM phosphorylates hSSB1 and prevents hSSB1 from ubiquitin-proteasome-mediated degradation. However, the E3 ligase that targets hSSB1 for destruction is still unknown. Here, we report that hSSB1 is the bona fide substrate for an Fbxl5-containing SCF (Skp1-Cul1-F box) E3 ligase. Fbxl5 interacts with and targets hSSB1 for ubiquitination and degradation, which could be prevented by ATM-mediated hSSB1 T117 phosphorylation. Furthermore, cells overexpression of Fbxl5 abrogated the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets and exhibited increased radiosensitivity, chemosensitivity and defective checkpoint activation after genotoxic stress stimuli. Moreover, the protein levels of hSSB1 and Fbxl5 showed an inverse correlation in lung cancer cells lines and clinical lung cancer samples. Therefore, Fbxl5 may negatively modulate hSSB1 to regulate DNA damage response, implicating Fbxl5 as a novel, promising therapeutic target for lung cancers.
Subject(s)
DNA Damage , DNA-Binding Proteins/metabolism , F-Box Proteins/metabolism , Mitochondrial Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Animals , Ataxia Telangiectasia Mutated Proteins/metabolism , Cell Line, Tumor , Cullin Proteins/metabolism , F-Box Proteins/physiology , Humans , Lung Neoplasms/enzymology , Lung Neoplasms/metabolism , Male , Mice, Nude , Phosphorylation , Proteolysis , Ubiquitin-Protein Ligase Complexes , Ubiquitin-Protein Ligases/physiology , UbiquitinationABSTRACT
The large tumour suppressor 1 (LATS1) signalling network has been proved to be an essential regulator within the cell, participating in multiple cellular phenotypes. However, it is unclear concerning the clinical significance of LATS1 and the regulatory mechanisms of 17-Allylamino-17- demethoxygeldanamycin (17-AAG) in lung adenocarcinoma (LAC). The aim of the present study was to investigate the correlation of LATS1 and yes-associated protein (YAP) expression with clinicopathological characteristics in LAC patients, and the effects of 17-AAG on biological behaviours of LAC cells. Subcutaneous LAC tumour models were further established to observe the tumour growth in nude mice. The results showed that the positive expression of LATS1 was significantly lowered (26.7% versus 68.0%, P < 0.001), while that of YAP was elevated (76.0% versus 56.0%, P = 0.03) in LAC tissues compared to the adjacent non-cancerous tissues; LAST1 expression was negatively correlated with YAP expression (r = 0.432, P < 0.001) and lymphatic invasion of the tumour (P = 0.015). In addition, 17-AAG inhibited proliferation and invasion, and induced cell apoptosis and cycle arrest in LAC cells together with increased expression of E-cadherin and p-LATS1, and decreased expression of YAP and connective tissue growth factor. Tumour volumes and weight were much smaller in 17-AAG-treated groups than those in untreated group (P < 0.01). Taken together, our findings indicate that decreased expression of LATS1 is associated with lymphatic invasion of LAC, and 17-AAG suppresses growth and invasion of LAC cells via regulation of the LATS1/YAP pathway in vitro and in vivo, suggesting that we may provide a promising therapeutic strategy for the treatment of human LAC.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Adenocarcinoma/drug therapy , Apoptosis/drug effects , Benzoquinones/pharmacology , Lactams, Macrocyclic/pharmacology , Lung Neoplasms/drug therapy , Phosphoproteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Adaptor Proteins, Signal Transducing/biosynthesis , Adenocarcinoma of Lung , Animals , Antineoplastic Agents/pharmacology , Cadherins/biosynthesis , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Connective Tissue Growth Factor/biosynthesis , Female , Gene Expression Regulation, Neoplastic , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Neoplasm Invasiveness/pathology , Phosphoproteins/biosynthesis , Protein Serine-Threonine Kinases/biosynthesis , Signal Transduction/drug effects , Transcription Factors , Xenograft Model Antitumor Assays , YAP-Signaling ProteinsABSTRACT
In most social species, the attainment of social dominance is strongly affected by personality traits. Dominant individuals show better cognitive abilities, however, whether an individual's cognition can determine its social status has remained inconclusive. We found that mice show better cognitive abilities tend to possess a higher social rank after cohousing. The dynamic release of acetylcholine (ACh) in the prelimbic cortex (PL) is correlated with mouse dominance behavior. ACh enhanced the excitability of the PL neurons via acetylcholine muscarinic M1 receptors (M1). Inhibition of M1 impaired mice cognitive performance and induced losing in social competition. Mice with M1 deficiency in the PL performed worse on cognitive behavioral tests, and exhibited lower status when re-grouped with others. Elevating ACh level in the PL of subordinate mice induced winning. These results provide direct evidence for the involvement of M1 in social hierarchy and suggest that social rank can be tuned by altering cognition through cholinergic system.
Subject(s)
Acetylcholine , Cognition , Hierarchy, Social , Mice, Inbred C57BL , Prefrontal Cortex , Receptor, Muscarinic M1 , Animals , Prefrontal Cortex/metabolism , Prefrontal Cortex/physiology , Receptor, Muscarinic M1/metabolism , Acetylcholine/metabolism , Male , Cognition/physiology , Mice , Mice, Knockout , Neurons/metabolism , Neurons/physiologyABSTRACT
Wound repair is a complex challenge for both clinical practitioners and researchers. Conventional approaches for wound repair have several limitations. Stem cell-based therapy has emerged as a novel strategy to address this issue, exhibiting significant potential for enhancing wound healing rates, improving wound quality, and promoting skin regeneration. However, the use of stem cells in skin regeneration presents several challenges. Recently, stem cells and biomaterials have been identified as crucial components of the wound-healing process. Combination therapy involving the development of biocompatible scaffolds, accompanying cells, multiple biological factors, and structures resembling the natural extracellular matrix (ECM) has gained considerable attention. Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells, providing them with an environment conducive to growth, similar to that of the ECM. These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing. This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing, emphasizing their capacity to facilitate stem cell adhesion, proliferation, differentiation, and paracrine functions. Additionally, we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.
ABSTRACT
Diabetic foot ulcers (DFUs) pose a critical medical challenge, significantly im-pairing the quality of life of patients. Adipose-derived stem cells (ADSCs) have been identified as a promising therapeutic approach for improving wound healing in DFUs. Despite extensive exploration of the mechanical aspects of ADSC therapy against DFU, its clinical applications remain elusive. In this review, we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of DFUs. The review begins with a discussion of the classification and clinical management of diabetic foot conditions. It then discusses the current landscape of clinical trials, focusing on their geographic distribution, reported efficacy, safety profiles, treatment timing, administration techniques, and dosing considerations. Finally, the review discusses the preclinical strategies to enhance ADSC efficacy. This review shows that many trials exhibit biases in study design, unclear inclusion criteria, and intervention protocols. In conclusion, this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches, with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.
ABSTRACT
The mechanisms of anxiety disorders, the most common mental illness, remain incompletely characterized. The ventral hippocampus (vHPC) is critical for the expression of anxiety. However, current studies primarily focus on vHPC neurons, leaving the role for vHPC astrocytes in anxiety largely unexplored. Here, genetically encoded Ca2+ indicator GCaMP6m and in vivo fiber photometry calcium imaging are used to label vHPC astrocytes and monitor their activity, respectively, genetic and chemogenetic approaches to inhibit and activate vHPC astrocytes, respectively, patch-clamp recordings to measure glutamate currents, and behavioral assays to assess anxiety-like behaviors. It is found that vHPC astrocytic activity is increased in anxiogenic environments and by 3-d subacute restraint stress (SRS), a well-validated mouse model of anxiety disorders. Genetic inhibition of vHPC astrocytes exerts anxiolytic effects on both innate and SRS-induced anxiety-related behaviors, whereas hM3Dq-mediated chemogenetic or SRS-induced activation of vHPC astrocytes enhances anxiety-like behaviors, which are reversed by intra-vHPC application of the ionotropic glutamate N-methyl-d-aspartate receptor antagonists. Furthermore, intra-vHPC or systemic application of the N-methyl-d-aspartate receptor antagonist memantine, a U.S. FDA-approved drug for Alzheimer's disease, fully rescues SRS-induced anxiety-like behaviors. The findings highlight vHPC astrocytes as critical regulators of stress and anxiety and as potential therapeutic targets for anxiety and anxiety-related disorders.
ABSTRACT
Introduction: Recombinant adeno-associated viruses (rAAVs) are widely used in genetic therapeutics. AAV5 has shown superior transduction efficiency, targeting neurons and glial cells in primate brains. Nonetheless, the comprehensive impact of AAV5 transduction on molecular and behavioral alterations remains unexplored. This study focuses on evaluating the effects of AAV5 transduction in the hippocampus, a critical region for memory formation and emotional processes. Methods: In this experiment, fluorescence-activated cell sorting (FACS) was utilized to isolate the mCherry-labeled pyramidal neurons in the hippocampus of CaMkIIα-cre mice following three different doses rAAV5-mCherry infusion after 3 weeks, which were then subjected to RNA sequencing (RNA-seq) to assess gene expression profiles. The cytokines concentration, mRNA expression, and glial response in hippocampi were confirmed by ELASA, digital droplet PCR and immunohistochemistry respectively. Locomotion and anxiety-like behaviors were elevated by Open Field Test and Elevated Plus Maze Test, while the Y-Maze were used to assessed spatial working memory. Recognition memory and fear responses were examined by the Novel Object Recognition Test and Fear Conditioning Test, respectively. Results: We found that 2.88 × 1010 v.g rAAV5 transduction significantly upregulated genes related to the immune response and apoptosis, and downregulated genes associated with mitochondrial function and synaptic plasticity in hippocampal pyramidal neurons, while did not induce neuronal loss and gliosis compared with 2.88 × 109 v.g and 2.88 × 108 v.g. Furthermore, the same doses impaired working memory and contextual fear memory, without effects on locomotion and anxiety-related behaviors. Discussion: Our findings highlight the detrimental impact of high-dose administration compared to median-dose or low-dose, resulting in increased neural vulnerability and impaired memory. Therefore, when considering the expression effectiveness of exogenous genes, it is crucial to also take potential side effects into account in clinical settings. However, the precise molecular mechanisms underlying these drawbacks of high-dose rAAV5-mCherry still require further investigation in future studies.
ABSTRACT
BACKGROUND AND OBJECTIVES: The objective of this study is to explore clinical risk factors for venous thromboembolism (VTE) in postoperative lung cancer patients in order to provide a basis for the prevention and treatment of postoperative VTE. METHODS: A total of 1,001 lung cancer patients were retrospectively analyzed. Each patient was confirmed with surgical pathology diagnosis and had a complete clinical and follow-up record. VTE was identified in a combination of spiral computed tomography (CT), pulmonary angiography, and color Doppler ultrasound. We used life table method to create an occurrence frequency curve of thrombosis. We also searched for high risk factors for postoperative VTE with Cox multivariate regression model and created frequency curves of thrombosis against different risk factors using Kaplan-Meier method. RESULTS: As of July 31, 2011, the median follow-up time is 25.73 ± 0.11 months (19.23-31.37). The cumulative frequency of VTE among 1,001 lung cancer patients is 2%, 3%, 4%, 5%, and 5.3% over 1, 3, 6, 12, and 30 months after the surgery. COX regression analysis showed that the hazard ratio of VTE occurrence in patients with incomplete resection relative to ones with complete resection is 9.867 (95% CI: 5.275-18.459, P = 0.000). And the hazard ratio of VTE occurrence is 3.472 (95% CI: 1.761-6.845, P = 0.000) in patients with anti-angiogenesis treatment compared to patients without such treatment. The hazard ratio of VTE occurrence is 2.808 (95% CI: 1.439-5.479, P = 0.002) in patients with EGFR-TKI treatment relative to patients without the treatment, and 7.520 (95% CI: 3.968-14.250, P = 0.000) in patients with an increase in D-dimer level relative to normal ones CONCLUSIONS: The highest incidence of VTE is within 1 month after lung cancer surgery. High risk factors for VTE include incomplete surgical resection, postoperative use of anti-angiogenesis drugs, EGFR-TKI application and an increase in preoperative D-dimer level.
Subject(s)
Lung Neoplasms/surgery , Postoperative Complications/etiology , Venous Thromboembolism/etiology , Adult , Aged , ErbB Receptors/antagonists & inhibitors , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk FactorsABSTRACT
OBJECTIVE: To measure the full-length anteroposterior and lateral radiographs of lower limbs after the resection of a tumor in the distal femur and tumor-type knee prosthesis replacement and to analyze the factors leading to aseptic loosening of the prosthesis. METHODS: A total of 26 cases of tumor-type knee prosthesis replacement or revision due to the distal femoral tumor at our hospital from January 2007 to December 2019 were retrospectively analyzed. The patients were divided into the loosening and unloosening groups depending on whether aseptic loosening occurred after surgery. Full-length anteroposterior and lateral radiographs of lower limbs were used to measure bone resection length, length of prosthesis, distance of proximal apex of the medullary stem of the femoral prosthesis from the maximum arc of the anterior femoral arch, diameter of the medullary stem, etc. Data were analyzed, and the risk factors for aseptic loosening of the prosthesis were explored. RESULTS: The ratio of the prosthetic length to the femoral length (63.72 ± 5.21) and the ratio of the femoral medullary stem diameter to the femoral diameter (26.03 ± 8.45) were smaller in the loosening group than in the unloosening group. The difference was statistically significant (p < 0.05). The distance between the apex of the medullary stem and the maximum arc of the anterior femoral arch was significantly shorter in the loosening group (3.47 ± 2.96) than in the unloosening group, and the difference was statistically significant (p < 0.05). The measurement of the lower limb alignment showed significant differences between the loosening and unloosening groups in terms of HKAA, mLDFA, and distance between the lower limb alignment and the center of the knee joint (p < 0.05). The logistic regression analysis showed that less than 30% ratio between the medullary stem diameter and the femoral diameter, less than 3 cm distance between the apex of the medullary stem and the maximum curvature of the anterior arch of the femur, distance between the lower limb alignment and the center of the knee joint, and presence of varus knee and valgus knee after the surgery were the risk factors for aseptic loosening of the prosthesis. CONCLUSIONS: The diameter of the femoral medullary stem of the prosthesis, the apex position of the prosthetic stem, and the lower limb alignment are the risk factors for aseptic loosening of the prosthesis.
Subject(s)
Arthroplasty, Replacement, Knee , Knee Prosthesis , Neoplasms , Femur/diagnostic imaging , Femur/surgery , Humans , Knee Joint/diagnostic imaging , Knee Joint/surgery , Lower Extremity/surgery , Neoplasms/surgery , Prosthesis Design , Prosthesis Failure , Reoperation , Retrospective StudiesABSTRACT
The Chinese government triggered the immediate implementation of a lockdown policy in China following the outbreak of the COVID-19 pandemic, leading to drastic decreases in air pollutant emissions. However, concentrations of PM2.5 and other pollutants increased during the COVID-19 lockdown over the Jing-Jin-Ji region compared with those averaged over 2015-2019, and two PM2.5 pollution events occurred during the lockdown. Using the ERA5 reanalysis data, we found that the Jing-Jin-Ji region during the COVID-19 lockdown was characterized by higher relative humidity, lower planetary boundary layer height, and anomalous updraft. These conditions were favorable for condensation and the secondary formation of aerosols and prevented turbulent diffusion of pollutants. Furthermore, we conducted sensitivity tests using the WRF-Chem model and found that ρ(PM2.5) increased by 20-55 µg·m-3(60%-170%) over the middle region of Jing-Jin-Ji during the COVID-19 lockdown due to changes in meteorological conditions. Furthermore, the enhanced aerosol chemistry and unfavorable diffusion conditions were identified as the key factors driving increases in PM2.5 concentrations during the lockdown. Planetary boundary layer height and relative humidity may become the important factors in forecasting PM2.5 pollution events over the Jing-Jin-Ji region under the background of emission reduction.