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PURPOSE: This comprehensive review aims to provide a unique clinical perspective on the latest advances and ongoing boron neutron capture therapy (BNCT) trials for various cancers. METHODS: We critically analyzed clinical data from BNCT trials for head and neck cancer, glioblastoma, melanoma, meningioma, breast cancer, and liver tumors. We investigated differences in tumor responses and normal tissue toxicities among trials and discussed potential contributing factors. We also identified the limitations of early BNCT trials and proposed strategies to optimize future trial design. RESULTS: BNCT has shown promising results in treating head and neck cancer, with high response rates and improved survival in patients with recurrent disease. In glioblastoma, BNCT combined with surgery and chemotherapy has demonstrated survival benefits compared to standard treatments. BNCT has also been successfully used for recurrent high-grade meningiomas and shows potential for melanomas, extramammary Paget's disease, and liver tumors. However, differences in tumor responses and toxicities were observed among trials, potentially attributable to variations in treatment protocols, patient characteristics, and evaluation methods. CONCLUSIONS: BNCT is a promising targeted radiotherapy for various cancers. Further optimization and well-designed randomized controlled trials are needed to establish its efficacy and safety. Future studies should focus on standardizing treatment protocols and addressing limitations to guide clinical decision-making and research priorities.

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Terapia por Captura de Neutrón de Boro , Terapia por Captura de Neutrón de Boro/métodos , Humanos , Neoplasias/radioterapia , Ensayos Clínicos como Asunto

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BACKGROUND: Insulin has been known to regulate bone metabolism, yet its specific molecular mechanisms during the proliferation and osteogenic differentiation of dental pulp stem cells (DPSCs) remain poorly understood. This study aimed to explore the effects of insulin on the bone formation capability of human DPSCs and to elucidate the underlying mechanisms. METHODS: Cell proliferation was assessed using a CCK-8 assay. Cell phenotype was analyzed by flow cytometry. Colony-forming unit-fibroblast ability and multilineage differentiation potential were evaluated using Toluidine blue, Oil red O, Alizarin red, and Alcian blue staining. Gene and protein expressions were quantified by real-time quantitative polymerase chain reaction and Western blotting, respectively. Bone metabolism and biochemical markers were analyzed using electrochemical luminescence and chemical colorimetry. Cell adhesion and growth on nano-hydroxyapatite/collagen (nHAC) were observed with a scanning electron microscope. Bone regeneration was assessed using micro-CT, fluorescent labeling, immunohistochemical and hematoxylin and eosin staining. RESULTS: Insulin enhanced the proliferation of human DPSCs as well as promoted mineralized matrix formation in a concentration-dependent manner. 10- 6 M insulin significantly up-regulated osteogenic differentiation-related genes and proteins markedly increased the secretion of bone metabolism and biochemical markers, and obviously stimulated mineralized matrix formation. However, it also significantly inhibited the expression of genes and proteins of receptors and receptor substrates associated with insulin/insulin-like growth factor-1 signaling (IIS) pathway, obviously reduced the expression of the phosphorylated PI3K and the ratios of the phosphorylated PI3K/total PI3K, and notably increased the expression of the total PI3K, phosphorylated AKT, total AKT and mTOR. The inhibitor LY294002 attenuated the responsiveness of 10- 6 M insulin to IIS/PI3K/AKT/mTOR pathway axis, suppressing the promoting effect of insulin on cell proliferation, osteogenic differentiation and bone formation. Implantation of 10- 6 M insulin treated DPSCs into the backs of severe combined immunodeficient mice and the rabbit jawbone defects resulted in enhanced bone formation. CONCLUSIONS: Insulin induces insulin resistance in human DPSCs and effectively promotes their proliferation, osteogenic differentiation and bone formation capability through gradually inducing the down-regulation of IIS/PI3K/AKT/mTOR pathway axis under insulin resistant states.

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Diferenciación Celular , Proliferación Celular , Pulpa Dental , Insulina , Osteogénesis , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Células Madre , Serina-Treonina Quinasas TOR , Pulpa Dental/citología , Pulpa Dental/metabolismo , Humanos , Osteogénesis/efectos de los fármacos , Insulina/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células Madre/metabolismo , Células Madre/citología , Células Madre/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proliferación Celular/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Diferenciación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ratones , Animales , Durapatita/farmacología , Células Cultivadas , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Colágeno

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OBJECTIVE: We aim to uncover the hot topics and development trends in clinical psychology research in the United States. METHOD: Utilizing bibliometric analysis, we examined clinical psychology papers published in the United States from 2010 to 2022 in the Web of Science database, employing citation analysis, content analysis, author analysis, and journal analysis. RESULTS: Our analysis revealed a significant increase in clinical psychology research, notably catalyzed by the 2019 COVID-19 pandemic. This surge was particularly evident in studies addressing mental disorders such as PTSD, anxiety, and suicidal behaviors, as well as psychological trauma related to issues like family conflict, elder abuse, and collective trauma. Furthermore, there was a distinct shift towards studying diverse populations, including gender and racial minorities, mothers, and adolescents. Therapeutic approaches, such as mindfulness-based practices and AI-assisted technologies, also gained prominence. CONCLUSIONS: This study represents the first large-scale bibliometric analysis in the field of clinical psychology in the United States. Our findings suggest that the COVID-19 pandemic highlights the importance of studying psychological issues linked to major events. Also, researchers are increasingly focusing on minority groups. This trend, along with the use of new technologies like big data and artificial intelligence, guides future research in clinical psychology. PUBLIC HEALTH SIGNIFICANCE STATEMENT: The works in this review suggest that the changing landscape of clinical psychology, especially post-COVID-19. The increased research post-pandemic emphasizes addressing psychological trauma arising from societal issues like family conflicts, elder abuse, and collective trauma. A positive shift towards inclusivity is evident in research, focusing on diverse groups like gender minorities, racial minorities, mothers, and adolescents. Additionally, the amplified focus on mental disorders like PTSD, anxiety, and suicidal behaviors during the pandemic stresses the need for tailored interventions and support systems. Exploring innovative methods such as mindfulness-based practices and AI-assisted technologies showcases the field's adaptability in mental health interventions.

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BACKGROUND: Substantial observational evidence suggests an association between neuropsychiatric conditions and venous thromboembolism (VTE). However, the causal relationship between these two conditions requires further investigation. Therefore, we used a two-sample Mendelian randomization (MR) approach to assess the bidirectional causal effects between four neuropsychiatric conditions and VTE, deep vein thrombosis, and pulmonary embolism (PE). METHODS: Genetic variants associated with four neuropsychiatric conditions (ie, schizophrenia, major depressive disorder [MDD], bipolar disorder, and epilepsy) and VTE, deep vein thrombosis, and PE were selected. Bidirectional univariable and multivariable MR methods were applied to evaluate the causal relationships among these conditions. The primary causal estimates were obtained using the inverse variance weighted method with multiplicative random effects, supplemented by MR Egger regression, weighted median, simple mode, and weighted mode. Sensitivity analysis was conducted using the MR pleiotropy residual sum, funnel plots, and outlier (MR pleiotropy and residual sum and outlier) method. RESULTS: Univariable MR results showed that genetic susceptibility to MDD increases the risk of VTE and PE (VTE: odds ratio [OR], 1.25; 95% confidence interval [CI], 1.08-1.46; P = .004; PE: OR, 1.36; 95% CI, 1.09-1.69; P = .006) and that PE has an adverse causal effect on MDD (OR, 1.02; 95% CI, 1.00-1.04; P = .026). Adjustment for confounders such as obesity, sleep duration, smoking, physical activity, and alcohol consumption revealed that increased genetic susceptibility to MDD is also associated with VTE and PE. CONCLUSIONS: Our results suggest that genetic susceptibility to MDD might have an adverse causal effect on the risk of VTE and PE and that PE has a reverse causal effect on MDD. Prevention and early diagnosis of depression are crucial in the management of VTE and PE.

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Background: Research on the risk factors for cervical cancer in Yunnan Province's four characteristic ethnic groups (Han, Bai, Dai, and Hani) is lacking. Objective: To study the risk factors of cervical cancer in four ethnic women in Yunnan Province, and to provide evidence for its prevention. Methods: The cervical cancer patients of Han, Bai, Dai and Hani ethnic groups in Yunnan Province who were first diagnosed in the Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center) from January 2011 to December 2020 were selected as the research objects. The 1:1 matched case-control study method was used, and single factor and conditional logistic regression were used for statistical analysis. Results: HPV types 16, 18 and 58 are mostly related with cervical cancer, the younger the age of the last pregnancy, the more times of pregnancy, childbirth and abortion, especially the younger the first marriage age of Bai and Dai, are the risk factors of cervical cancer; the infection of genital tract bacteria, mycoplasma and chlamydia is closely related to the incidence of cervical cancer in four ethnicities. Multifactorial analysis showed that demographic characteristics and environment/behavior were not included in the influencing factors of cervical cancer; among Han, Bai, Dai and Hani ethnic minorities, contraception (OR=0.29, OR=0.03, OR=0.09, OR=0.16, P<0.05) was positive factor, HPV infection (OR=64.77, OR=128.71, OR=71.89, OR=40.07, P<0.01) was a causative factor of cervical cancer. Conclusion: Risk of high parity with cervical cancer could be due to a complex interplay of factors, it is very important to formulate prevention strategies and measures in line with the cervical cancer of Han, Bai, Dai and Hani ethnic groups women in Yunnan Province.

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The ischemic stroke is a major global health concern, with high mortality and disability rates. Unfortunately, there is a dearth of effective clinical interventions for managing poststroke neuroinflammation and blood-brain barrier (BBB) disruption that are crucial for the brain injury evolving and neurological deficits. By leveraging the pathological progression of an ischemic stroke, we developed an M2 microglia-targeting lipid nanoparticle (termed MLNP) approach that can selectively deliver mRNA encoding phenotype-switching interleukin-10 (mIL-10) to the ischemic brain, creating a beneficial feedback loop that drives microglial polarization toward the protective M2 phenotypes and augments the homing of mIL-10-loaded MLNPs (mIL-10@MLNPs) to ischemic regions. In a transient middle cerebral artery occlusion (MCAO) mouse model of an ischemic stroke, our findings demonstrate that intravenously injected mIL-10@MLNPs induce IL-10 production and enhance the M2 polarization of microglia. The resulting positive loop reinforces the resolution of neuroinflammation, restores the impaired BBB, and prevents neuronal apoptosis after stroke. Using a permanent distal MCAO mouse model of an ischemic stroke, the neuroprotective effects of mIL-10@MLNPs have been further validated by the attenuation of the sensorimotor and cognitive neurological deficits. Furthermore, the developed mRNA-based targeted therapy has great potential to extend the therapeutic time window at least up to 72 h poststroke. This study depicts a simple and versatile LNP platform for selective delivery of mRNA therapeutics to cerebral lesions, showcasing a promising approach for addressing an ischemic stroke and associated brain conditions.

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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Ratones , Animales , Microglía/patología , Microglía/fisiología , Barrera Hematoencefálica/patología , Isquemia Encefálica/tratamiento farmacológico , Enfermedades Neuroinflamatorias , Accidente Cerebrovascular/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/patología

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Background: Abnormal anillin (ANLN) expression has been observed in multiple tumours and is closely associated with patient prognosis and clinical features. In this study, we systematically elucidated the clinical significance and biological roles of ANLN in patients with clear cell renal cell carcinoma (ccRCC). Methods: We obtained transcriptome and clinical data of patients with ccRCC from public databases. Multi-omics data and clinical samples were combined to analyse the correlation between ANLN expression and the clinical characteristics of patients with renal cancer. Additionally, the immune cell landscape of ANLN expression was evaluated using different immune algorithms in the tumour microenvironment. The tumour-promoting potential of ANLN was confirmed using in vitro assays, including CCK8 and Transwell assays. Results: Bioinformatics analysis showed that ANLN is over-expressed in patients with ccRCC, as validated by clinical samples. Publicly available clinical data suggest that high ANLN expression may indicate poor outcomes in patients with ccRCC. Moreover, biological function analysis revealed a marked enrichment of the cell cycle and PI3K-Akt pathways. The distribution of immune cells, particularly M2 macrophages, differed in patients with ccRCC. Furthermore, ANLN silencing inhibited the proliferation, migration, and invasion of renal cancer cells in vitro. After ANLN expression was knocked down in 786-O cells, the protein levels of important PI3K signalling pathway components, including PI3K, Akt, and mTOR, drastically decreased. Conclusions: These findings suggest that ANLN is dysregulated in renal cancer tissues and promotes tumour progression by activating the PI3K/Akt/mTOR signalling pathway.

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Cholesteatoma is a noncancerous cystic lesion caused by an abnormal growth of keratinizing squamous epithelium which is invasive and capable of destroying structures. A prospective study on the expression of membrane type1-matrix metalloproteinases (MMP-14) and its related influencing factors in middle ear cholesteatoma was conducted to fully understand the pathogenesis of cholesteatoma in the molecular level. We examined the expression of MMP-14 by immunohistochemical staining 39 middle ear cholesteatoma specimens and 10 external auditory meatus epithelial cell specimens. The cholesteatoma specimens were divided into 4 groups according to the degree of destruction of the ossicles during surgery. The associated factors affecting MMP-14 expression were analyzed using statistical methods; The positive expression of MMP-14 in the epithelium of the external auditory canal was significantly different between middle ear cholesteatoma and normal patients (P < .05); Gender, age, and the degree of hearing loss had no statistically significant effect on MMP-14 expression (P > .05); The expression of MMP-14 was positively correlated with the severity of bone destruction (R = 0.535, P < .05); MMP-14 plays an important role in the pathological development of the epithelium of cholesteatoma; MMP-14 expression in middle ear cholesteatoma tissue was not strongly correlated with the level of hearing loss, age or gender, but was positively correlated with the degree of middle ear bone destruction.

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Colesteatoma del Oído Medio , Sordera , Osteólisis , Humanos , Colesteatoma del Oído Medio/metabolismo , Colesteatoma del Oído Medio/patología , Sordera/patología , Oído Medio/patología , Epitelio/metabolismo , Metaloproteinasa 14 de la Matriz/metabolismo , Osteólisis/patología , Estudios Prospectivos

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Phosphatidylinositol 3-kinase delta (PI3Kδ) and gamma (PI3Kγ) are predominantly located in immune and hematopoietic cells. It is well-established that PI3Kδ/γ plays important roles in the immune system and participates in inflammation; hence, it could be a potential target for anti-inflammatory therapy. Currently, several PI3K inhibitors are used clinically to treat cancers with aberrant PI3K signaling; however, their role in treating acute respiratory inflammatory diseases has rarely been explored. Herein, we investigated the potential anti-inflammatory activities of several pharmacological PI3K inhibitors, including marketed drugs idelalisib (PI3Kδ), duvelisib (PI3Kδ/γ), and copanlisib (pan-PI3K with preferential α/δ) and the clinical drug eganelisib (PI3Kγ), for treating acute lung injury (ALI). In the lipopolysaccharide-induced RAW264.7 macrophage inflammatory model, the four inhibitors significantly suppressed proinflammatory cytokine expression by inhibiting the PI3K signaling pathway. Oral administration of PI3K inhibitors markedly improved lung injury in a murine model of ALI. PI3K pathway inhibition decreased inflammatory cell infiltration and totalprotein levels, as well as reduced the expression of associated lung inflammatory factors. Collectively, all four representative PI3K inhibitors exerted prominent anti-inflammatory properties, indicating that PI3K δ and/or γ inhibition could be ideal targets to treat respiratory inflammatory diseases by reducing the inflammatory response. The findings of the current study provide a new basis for utilizing PI3K inhibitors to treat acute respiratory inflammatory diseases.

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Lesión Pulmonar Aguda , Fosfatidilinositol 3-Quinasas , Ratones , Animales , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Lesión Pulmonar Aguda/tratamiento farmacológico

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Atherosclerosis is a common pathology present in many cardiovascular diseases. Although the current therapies (including statins and inhibitors of the serine protease PCSK9) can effectively reduce low-density lipoprotein (LDL) cholesterol levels to guideline-recommended levels, major adverse cardiovascular events still occur frequently. Indeed, the subendothelial retention of lipoproteins in the artery wall triggers multiple events of inflammation in macrophages and is a major contributor to the pathological progression of atherosclerosis. It has been gradually recognized that modulating inflammation is, therefore, an attractive avenue to forestall and treat atherosclerosis and its complications. Unfortunately, challenges with specificity and efficacy in managing plaque inflammation have hindered progress in atherosclerosis treatment. Herein, we report an NP-mediated mRNA therapeutic approach to target atherosclerotic lesional macrophages, modulating inflammation in advanced atherosclerotic lesions for the treatment of atherosclerosis. We demonstrated that the targeted NPs containing IL-10 mRNA colocalized with M2-like macrophages and induced IL-10 production in atherosclerotic plaques following intravenous administration to Western diet (WD)-fed Ldlr-/- mice. Additionally, the lesions showed a significantly alleviated inflammatory response, as evidenced by reduced oxidative stress and macrophage apoptosis, resulting in decreased lipid deposition, diminished necrotic areas, and increased fiber cap thickness. These results demonstrate the successful delivery of mRNA therapeutics to macrophage-enriched plaques in a preclinical model of advanced atherosclerosis, showing that this targeted NP inflammation management approach has great potential for translation into a wide range of clinical applications.

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Aterosclerosis , Placa Aterosclerótica , Animales , Ratones , Placa Aterosclerótica/tratamiento farmacológico , Proproteína Convertasa 9 , Interleucina-10 , Aterosclerosis/tratamiento farmacológico , Inflamación

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Since dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway is associated with the pathogenesis of cancer, inflammation, and autoimmunity, PI3K has emerged as an attractive target for drug development. Although copanlisib is the first pan-PI3K inhibitor to be approved for clinical use, the precise mechanism by which it acts on PI3K has not been fully elucidated. To reveal the binding mechanisms and structure-activity relationship between PI3K and copanlisib, a comprehensive modeling approach that combines 3D-quantitative structure-activity relationship (3D-QSAR), pharmacophore model, and molecular dynamics (MD) simulation was utilized. Initially, the structure-activity relationship of copanlisib and its derivatives were explored by constructing a 3D-QSAR. Then, the key chemical characteristics were identified by building common feature pharmacophore models. Finally, MD simulations were performed to elucidate the important interactions between copanlisib and different PI3K subtypes, and highlight the key residues for tight-binding inhibitors. The present study uncovered the principal mechanism of copanlisib's action on PI3K at the theoretical level, and these findings might provide guidance for the rational design of pan-PI3K inhibitors.Communicated by Ramaswamy H. Sarma.

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The alveolar bone marrow mesenchymal stem cells (ABM-MSCs) play an important role in oral bone healing and regeneration. Insulin is considered to improve impaired oral bones due to local factors, systemic factors and pathological conditions. However, the effect of insulin on bone formation ability of ABM-MSCs still needs to be elucidated. The aim of this study was to determine the responsiveness of rat ABM-MSCs to insulin and to explore the underlying mechanism. We found that insulin promoted ABM-MSCs proliferation in a concentration-dependent manner, in which 10-6 M insulin exerted the most significant effect. 10-6 M insulin significantly promoted the type I collagen (COL-1) synthesis, alkaline phosphatase (ALP) activity, osteocalcin (OCN) expression, and mineralized matrix formation in ABM-MSCs, significantly enhanced the gene and protein expressions of intracellular COL-1, ALP, and OCN. Acute insulin stimulation significantly promoted insulin receptor (IR) phosphorylation, IR substrate-1 (IRS-1) protein expression, and mammalian target of rapamycin (mTOR) phosphorylation, but chronic insulin stimulation decreased these values, while inhibitor NT219 could attenuate these responses. When seeded on ß-tricalcium phosphate (ß-TCP), ABM-MSCs adhered and grew well, during the 28-day culture period, ABM-MSCs+ß-TCP +10-6 M insulin group showed significantly higher extracellular total COL-1 amino-terminus prolongation peptide content, ALP activity, OCN secretion, and Ca and P concentration. When implanted subcutaneously in severe combined immunodeficient mice for 1 month, the ABM-MSCs+ß-TCP +10-6 M insulin group obtained the most bone formation and blood vessels. These results showed that insulin promoted the proliferation and osteogenic differentiation of ABM-MSCs in vitro, and enhance osteogenesis and angiogenesis of ABM-MSCs in vivo. Inhibition studies demonstrated that the insulin-induced osteogenic differentiation of ABM-MSCs was dependent of insulin/mTOR signaling. It suggests that insulin has a direct anabolic effect on ABM-MSCs.

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Células Madre Mesenquimatosas , Osteogénesis , Ratones , Ratas , Animales , Insulina/farmacología , Insulina/metabolismo , Diferenciación Celular , Colágeno/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Células de la Médula Ósea , Células Cultivadas , Fosfatasa Alcalina/metabolismo , Mamíferos/metabolismo

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Objective: The aim of this study was to explore the correlation and difference of influencing factors by analyzing the psychological status of patients with cervical precancerous lesions and cancer in Han and Ethnic minorities. So as to provide evidence for more targeted psychological intervention for categories types of patients. Methods: The Chinese version of Kessler 10 scale was used to investigate 200 Han Chinese patients with cervical lesions and 100 ethnic minority patients with cervical lesions in Yunnan Cancer Center. Statistical analysis was performed using t-test, analysis of variance, and multivariable linear regression. Results: There was no significant difference in the distribution of demographic characteristics between the two groups (P > 0.05).The results of univariate analysis showed that the impression of K10 score was statistically significant among the following factors: educational level, awareness of HPV vaccine, disease screening status, employee medical insurance, economic burden of disease, cancerous or not, pathological type, treatment modalities, marital status, and family genetic history of tumor (P < 0.05). After multivariate analysis and considering the influence of the number of independent variables, it indicates that the economic burden of the disease, occupation, and family genetic history of tumor had a greater impact on the total score of Han patients among many factors, accounting for a total of 8.1%(Adj R2 = 0.081).Treatment modalities had the greatest effect on the scores of ethnic minority patients, accounting for 8.4%(Adj R2 = 0.084). Conclusion: The factors affecting the psychological status of patients between the two groups have similarities and differences. Multifactorial analysis showed that the main factors affecting the psychology of Han patients were: economic burden caused by the disease, occupation, and family genetic history of tumor; while the main factors affecting the psychology of minority patients were: treatment modalities. Therefore, targeted recommendations and policy measures can be proposed respectively.

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Polymyositis (PM) and dermatomyositis (DM) are the two subtypes of idiopathic inflammatory myositis and are characterized as symmetrical progressive muscle weakness in the proximal extremities. PM/DM affect multiple organs and systems, including the cardiovascular, respiratory and digestive tract systems. An in-depth understanding of PM/DM biomarkers will facilitate development of simple and accurate strategies for diagnosis, treatment, and prognosis prediction. This review summarized the classic biomarkers of PM/DM, including anti-aminoacyl tRNA synthetases (ARS) antibody, anti-Mi-2 antibody, anti-melanoma differentiation-associated gene 5 (MDA5) antibody, anti-transcription intermediary factor 1-γ (TIF1-γ) antibody, anti-nuclear matrix protein 2 (NXP2) antibody, among others. Among them, anti-aminoacyl tRNA synthetases antibody is the most classic. In addition, many potential novel biomarkers were also discussed in this review, including anti-HSC70 antibody, YKL-40, interferons, myxovirus resistance protein 2, regenerating islet-derived protein 3-α, interleukin (IL)-17, IL-35, microRNA (miR)-1 and so on. Among the biomarkers of PM/DM described in this review, classic biomarkers have become the mainstream biomarkers to assist clinicians in diagnosis due to their early discovery, in-depth research, and widespread application. The novel biomarkers also have potential and broad research prospects, which will make immeasurable contributions to exploring biomarker-based classification standards and expanding their application value.

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Dermatomiositis , Polimiositis , Humanos , Dermatomiositis/diagnóstico , Polimiositis/diagnóstico , Biomarcadores , Autoanticuerpos , Ligasas , ARN de Transferencia , Estudios Retrospectivos

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BACKGROUND: Cervical cancer is the fourth most diagnosed cancer and the leading cause of cancer death, and it still poses a crippling threat to women's health. China launched the National Cervical Cancer Screening Program for Rural Women in 2009, and an increasing number of cervical cancer patients have been detected. Health-related quality of life is not only the end point of cancer research but is also related to socioeconomic and clinical factors and has received an increasing amount of attention. In light of the characteristics of the Yunnan nationality, we conducted cross-sectional research to assess and explore the health-related quality of life in both Han and ethnic minority patients. METHODS: A cross-sectional study was conducted from January 2020 to May 2021 at the Third Affiliated Hospital of Kunming University/Yunnan Cancer Hospital. Patients, including 100 Han patients and 100 ethnic minorities, were interviewed using the FACT-Cx questionnaire within 3 months of receiving treatment. RESULTS: Patients of Han ethnicity and ethnic minorities were comparable in both sociodemographic and clinical features. The total FACT-Cx scores were 139.38 ± 9.83 and 134.39 ± 13.63 in Han and ethnic minority patients, respectively (P < 0.05). Significant differences were shown in physical well-being, emotional well-being and the FACT-Cx subscale between the Han and ethnic minority groups. Independent predictors of the FACT-Cx scale were ethnicity, educational level, participation in the National Cervical Cancer Screening Program for Rural Areas (NCCSPRA) and clinical stage. CONCLUSIONS: The results of our study imply that the HRQOL of Han patients is better than that of ethnic minority patients. Thus, clinicians and related health workers should pay more attention to the HRQOL of cervical cancer patients, especially for ethnic minority patients, and provide psychosocial interventions as much as possible to improve their HRQOL. Policies should also aim to strengthen health education regarding cervical cancer and expand the coverage of the NCCSPRA among those who are ethnic minorities, are older and have low educational levels.

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Etnicidad , Neoplasias del Cuello Uterino , Humanos , Femenino , Etnicidad/psicología , China , Grupos Minoritarios , Minorías Étnicas y Raciales , Estudios Transversales , Calidad de Vida/psicología , Detección Precoz del Cáncer

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Neuroinflammation has been identified as another significant pathogenic factor in Alzheimer's disease following Aß amyloid deposition and tau protein hyperphosphorylation, activated in the central nervous system by glial cells in response to injury-related and pathogen-related molecular patterns. Moderate glial cell activity can be neuroprotective; however, excessive glial cell activation advances the pathology of Alzheimer's disease and is accompanied by structural changes in the brain interface, with peripheral immune cells entering the brain through the blood-brain barrier, creating a vicious circle. The immunomodulatory properties of mesenchymal stem cells (MSCs) are primarily conveyed through extracellular vesicles (EVs). MSC-EVs participate in chronic inflammatory and immune processes by transferring nucleic acids, proteins and lipids from the parent cell to the recipient cell, thus MSC-EVs retain their immunomodulatory capacity while avoiding the safety issues associated with living cell therapy, making them a promising focus for immunomodulatory therapy. In this review, we discuss the modulatory effects of MSC-EVs on Alzheimer's disease-associated immune cells and the mechanisms involved in their treatment of the condition. We have found a clinical trial of MSC-EVs in Alzheimer's disease treatment and outlined the challenges of this approach. Overall, MSC-EVs have the potential to provide a safe and effective treatment option for Alzheimer's disease by targeting neuroinflammation.

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Enfermedad de Alzheimer , Vesículas Extracelulares , Células Madre Mesenquimatosas , Humanos , Enfermedad de Alzheimer/terapia , Enfermedades Neuroinflamatorias , Inmunomodulación

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Background: We investigated the application of local perforator flap or island flap with a modified triangular to repair small and medium facial defects. Methods: (1) Before the operation, a Doppler flowmeter was used to investigate the superficial exit point of the perforator artery. The length to breadth ratio of the flap was more than 3-4 times, and it contained 1-2 perforator vessels. (2) The lesion was excised, and the skin was cut along the design line of the flap. The flap was separated and trimmed based on the defect degree. (3) The blood supply was confirmed, and the defect was then covered with the flap by "rotation and advancement" approach without causing tension. The incision was finally sutured in layers. (4) Postoperative routine care was performed according to the situation. Results: The functional morphology and appearance of all 23 cases of skin flaps successfully recovered during follow-up. There was no major aesthetic and malformation recorded. Conclusion: In summary, the modified triangular perforator flap can improve the functional appearance at the repaired small and medium facial defects.

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Phosphatidylinositol 3-kinase gamma (PI3Kγ) plays a critical role in immune signaling, thus identifying PI3Kγ as a potential therapeutic target. However, developing selective PI3Kγ inhibitors is hampered by the highly conserved structure of the ATP-binding pocket. Focused effort would be needed to improve upon the γ-subtype selectivity of the inhibitors; therefore, in the present study, a naïve Bayesian classification (NBC) model with PI3Kγ structural features that integrates molecular docking and pharmacophore based on multiple PI3Kγ conformations was developed for virtual screening against PI3Kγ to find novel selective PI3Kγ inhibitors. First, the active PI3Kγ inhibitors/decoy dataset was used to prove whether molecular docking or pharmacophore, integrating multiple PI3Kγ conformations always has higher prediction accuracy than that of any single conformation. Second, both internal cross-validation and external prediction revealed that the NBC model combining molecular docking and pharmacophore could significantly improve the enrichment of active PI3Kγ inhibitors. Then, an analog dataset based on JN-PK1 (a reference compound) was constructed and submitted to virtual screening using the optimal NBC model. Finally, a novel inhibitor with higher PI3Kγ inhibitory activity than JN-PK1 was identified through a series of biological assays, showing both good accuracy and significant reliability of the NBC model with the PI3Kγ structural features. We hope that the developed virtual screening strategy will provide valuable guidance for the discovery of novel selective PI3Kγ inhibitors.

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Fosfatidilinositol 3-Quinasa , Relación Estructura-Actividad Cuantitativa , Simulación del Acoplamiento Molecular , Teorema de Bayes , Reproducibilidad de los Resultados , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Dominio Catalítico , Ligandos

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Ionizable cationic lipid-containing lipid nanoparticles (LNPs) are the most clinically advanced non-viral gene delivery platforms, holding great potential for gene therapeutics. This is exemplified by the two COVID-19 vaccines employing mRNA-LNP technology from Pfizer/BioNTech and Moderna. Herein, we develop a chemical library of ionizable cationic lipids through a one-step chemical-biological enzyme-catalyzed esterification method, and the synthesized ionizable lipids were further prepared to be LNPs for mRNA delivery. Through orthogonal design of experiment methodology screening, the top-performing AA3-DLin LNPs show outstanding mRNA delivery efficacy and long-term storage capability. Furthermore, the AA3-DLin LNP COVID-19 vaccines encapsulating SARS-CoV-2 spike mRNAs successfully induced strong immunogenicity in a BALB/c mouse model demonstrated by the antibody titers, virus challenge, and T cell immune response studies. The developed AA3-DLin LNPs are an excellent mRNA delivery platform, and this study provides an overall perspective of the ionizable cationic lipids, from aspects of lipid design, synthesis, screening, optimization, fabrication, characterization, and application.

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COVID-19 , Nanopartículas , Ratones , Animales , Humanos , ARN Mensajero/genética , ARN Mensajero/química , Vacunas contra la COVID-19 , Lípidos/química , COVID-19/prevención & control , SARS-CoV-2/genética , Nanopartículas/química , Liposomas , Cationes , Catálisis

RESUMEN

Background: Clopidogrel is a traditional P2Y12 receptor inhibitor that is widely used in clinical practice, but there are significant individual differences in its therapeutic effect. Carriers of the CYP2C19 deletion allele have a higher risk of adverse cardiovascular events than non-carriers. Methods: In this study, 170 patients diagnosed with coronary heart disease (CHD) and on regular oral clopidogrel or ticagrelor antiplatelet therapy in the Department of Cardiology of Wuxi Second People's Hospital from August to December 2019 were screened. Baseline patient data were collected, percutaneous coronary angiography (CAG) or coronary computed tomography angiography (CTA) results were recorded, CYP2C19 gene type was detected, and prognosis/outcome was assessed by telephone/outpatient/inpatient follow-up for 12 months. Results: (I) Of the 170 patients, 0.66% were the fast metabolic type, 41.45% were the normal metabolic type, 42.76% were the intermediate metabolic type, and 15.13% were the poor metabolic type. CYP2C19*2 mutation accounted for 89.29% of all mutations, CYP2C19*3 mutation accounted for 9.82%, and CYP2C19*17 mutation accounted for only 0.89%. (II) Among the patients with CHD who regularly took clopidogrel, the risk in the intermediate metabolic group was 5.208-fold higher than that of normal metabolic group, and that of the poor metabolic group was 3.75-fold higher than that of normal metabolic group; there was no significant difference between the intermediate and poor metabolic groups. (III) Prognosis was significantly associated with regular use of ticagrelor or clopidogrel by patients in the intermediate metabolic group. There was no significant correlation between poor metabolism (PM) and normal metabolism (NM). Prognosis was significantly associated with regular use of ticagrelor or clopidogrel in patients undergoing percutaneous coronary intervention (PCI), but not in patients who did not undergo PCI. Conclusions: CYP2C19 polymorphism was associated with the prognosis of patients with CHD administered antiplatelet therapy with oral clopidogrel. The incidence of poor prognosis was significantly increased with CYP2C19*2 and/or CYP2C19*3 mutations, and patients undergoing PCI or carrying a single CYP2C19 deletion allele had a better prognosis with ticagrelor as replacement therapy.