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Background: Distinguishing benign from malignant sub-centimeter solid pulmonary nodules (SSPNs) continues to be challenging in clinical practice. Earlier diagnosis is crucial for improving patient survival and prognosis. This study aimed to investigate the risk factors of malignant SSPNs and establish and validate a prediction model based on computed tomography (CT) characteristics to assist in their early diagnosis. Methods: A total of 261 consecutive participants with 261 SSPNs were retrospectively recruited between January 2012 and July 2023 from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Center 1), including 161 malignant lesions and 100 benign lesions. Patients were randomly assigned to the training set (n=183) and validation set (n=78) according to a 7:3 ratio. Malignant nodules were confirmed by pathology; and benign nodules were confirmed by follow-up or pathology. Clinical data and CT features were collected to estimate the independent predictors of malignancy of SSPN with multivariate logistic analysis. A clinical prediction model was subsequently established by logistic regression. Furthermore, an additional 69 consecutive patients with 69 SSPNs from The Fourth Hospital of Hebei Medical University (Center 2) between January 2022 and December 2022 were retrospectively included as an external cohort to validate the predictive efficacy of the model. The performance of the prediction model was assessed by sensitivity, specificity, and the area under the receiver operating characteristic curve. Results: There were 113 (61.7%), 48 (61.5%) and 28 (40.6%) malignant SSPNs in the training, internal and external validation sets, respectively. Multivariate logistic analysis revealed four independent predictors of malignant SSPNs: tumor-lung interface (P=0.002), spiculation (P=0.04), air bronchogram (P=0.047), and invisible at the mediastinal window (P=0.003). The area under the curve (AUC) for the prediction model in the training set was 0.875 [95% confidence interval (CI): 0.818, 0.933]; and the sensitivity and specificity were 94.7% and 68.6%, respectively. The AUCs in the internal and external validation set were (0.781; 95% CI: 0.664, 0.897) and (0.873; 95% CI: 0.791, 0.955), respectively; the sensitivity and specificity were 66.7% and 83.3% for the internal validation data, and 100.0% and 61.0% for the external validation data, respectively. Conclusions: The prediction model based on CT characteristics could be helpful for distinguishing malignant SSPNs from benign ones.
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In this study, our objective was to investigate the impact of dietary butyric acid (BA) on the homeostasis mechanism of Pacific shrimp under cold stress. Specifically, we analyzed its effects on immunity, antioxidant capacity, gene expression, and metabolomics response. To carry out this research, Litopenaeus vannamei were fed a diet supplemented with BA for 8 weeks. Following this feeding period, a total of 180 shrimp, with an average weight of 12.76 ± 0.38 g, were exposed to cold conditions, with the temperature decreasing from 28 °C to 14 °C within an hour. The results of our study revealed survival rates ranging from 90 % to 100 %. Shrimp that were fed a diet containing 1.5 % BA exhibited a significant increase in acid phosphatase (ACP) and alkaline phosphatase (AKP) activity. Conversely, the control groups showed an increase in aspartate aminotransferase (AST) and alanine transaminase (ALT) activity. Shrimp that consumed diets containing 1.5 % BA displayed the lowest malondialdehyde (MDA) levels with the highest superoxide dismutase (SOD) content. The shrimp fed the BA diet exhibited tightly organized hepatic tubules with a star-shaped lumen filled with numerous B and R cells. Furthermore, shrimp fed the BA diet demonstrated a significant increase in caspase 3 (CASP) expression. There were no significant variations in the expression levels of prophenoloxidase (ProPO), manganese superoxide dismutase (MnSOD), and glutathione S-transferase (GST) The metabolites of Dl-carnitine, acetyl-l-carnitine, propionylcarnitine, hexanoylcarnitine, palmitoylcarnitine, decanoylcarnitine, and Dl-carnitine exhibited significantly increased expression in shrimp that were fed BA, suggesting their role in the lipolysis process. Based on the findings, adding 2 % BA to the diet of Pacific shrimp helps reduce inflammation and oxidative stress when they are under cold stress.
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Skeletal muscle is an important motor organ with multinucleated myofibers as its smallest cellular units. Myofibers are formed after undergoing cell differentiation, cell-cell fusion, myonuclei migration, and myofibril crosslinking among other processes and undergo morphological and functional changes or lesions after being stimulated by internal or external factors. The above processes are collectively referred to as myogenesis. After myofibers mature, the function and behavior of skeletal muscle are closely related to the voluntary movement of the body. In this review, we systematically and comprehensively discuss the physiological and pathological processes associated with skeletal muscles from five perspectives: molecule basis, myogenesis, biological function, adaptive changes, and myopathy. In the molecular structure and myogenesis sections, we gave a brief overview, focusing on skeletal muscle-specific fusogens and nuclei-related behaviors including cell-cell fusion and myonuclei localization. Subsequently, we discussed the three biological functions of skeletal muscle (muscle contraction, thermogenesis, and myokines secretion) and its response to stimulation (atrophy, hypertrophy, and regeneration), and finally settled on myopathy. In general, the integration of these contents provides a holistic perspective, which helps to further elucidate the structure, characteristics, and functions of skeletal muscle.
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Tumor-infiltrating CD4+ T cells orchestrate the adaptive immune response through remarkable plasticity, and the expression patterns of exhaustion-related inhibitory receptors in these cells differ significantly from those of CD8+ T cells. Thus, a better understanding of the molecular basis of CD4+ T cell exhaustion and their responses to immune checkpoint blockade (ICB) is required. Here, we integrated multiomics approaches to define the phenotypic and molecular profiles of exhausted CD4+ T cells in oropharyngeal squamous cell carcinoma (OPSCC). Two distinct immune-promoting (Module 1) and immunosuppressive (Module 2) functional modules in tumor-infiltrating CD4+ T cells were identified, and both the immune-promoting function of Module 1 cells and immunosuppressive function of Module 2 cells were positively associated with their corresponding exhaustion states. Furthermore, the application of ICBs targeting effector CD4+ T cells in Module 1 (αPD-1) and Treg cells in Module 2 (αCTLA-4) in mouse models could help reinvigorate the effector function of Module 1-exhausted CD4+ T cells and reduce the immunosuppressive function of Module 2-exhausted CD4+ T cells, ultimately promoting OPSCC tumor regression. Taken together, our study provides a crucial cellular basis for the selection of optimal ICB in treating OPSCC.
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PURPOSE: This study aimed to develop and validate a new model that focused on the risk of imminent vertebral fractures in women with osteoporosis. METHODS: Data from 2,048 patients were extracted from three hospitals, of which 1,720 patients passed the inclusion and exclusion screen. The patients from Nanfang Hospital (NFH) were randomized at a 2:1 ratio to create a training cohort (n = 709) and an internal validation cohort (n = 355), with the patients from the other two hospitals (n = 656) used for external validation. The risk factors included in the imminent osteoporotic vertebral compression fractures (OVCFs) prediction model (labelled TVF) were sorted by the least absolute shrinkage and selection operator and constructed by logistic regression. The area under the receiver operating characteristic curve (AUC), the decision curve, and the clinical impact curves of the optimal model were analyzed to verify the model. RESULTS: There were 138 and 161 fresh fractures in NFH and the other two hospitals, respectively. The lowest BMD T value and the history of vertebral fracture were integrated into the TVF model. The prediction power of TVF was demonstrated by the AUCs of 0.788 (95% confidence interval [CI], 0.728-0.849) in the training cohort and 0.774 (95% CI, 0.705-0.842) in the internal validation cohort, and 0.790 (95% CI, 0.742-0.839) and 0.741 (95% CI, 0.668-0.813) in the external validation cohorts. CONCLUSION: The TVF model demonstrated good discrimination to stratify the imminent risk of OVCFs. We therefore consider the model as a pertinent commencement in the search for more accurate imminent OVCFs prediction.
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BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).
Subject(s)
Amoxicillin , Anti-Bacterial Agents , Bismuth , Clarithromycin , Drug Administration Schedule , Drug Therapy, Combination , Helicobacter Infections , Helicobacter pylori , Sulfonamides , Tetracycline , Humans , Helicobacter Infections/drug therapy , Helicobacter Infections/diagnosis , Helicobacter pylori/drug effects , Middle Aged , Male , Female , Tetracycline/administration & dosage , Tetracycline/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Bismuth/administration & dosage , Bismuth/therapeutic use , Bismuth/adverse effects , Adult , Clarithromycin/administration & dosage , Amoxicillin/administration & dosage , Sulfonamides/administration & dosage , Pyrroles/administration & dosage , Pyrroles/adverse effects , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/adverse effects , Breath Tests , Treatment Outcome , Aged , ChinaABSTRACT
This study looked at the effects of adding butyric acid (BA) to the diets of juvenile Pacific shrimp and how it affected their response to survival, immunity, histopathological, and gene expression profiles under heat stress. The shrimp were divided into groups: a control group with no BA supplementation and groups with BA inclusion levels of 0.5 %, 1 %, 1.5 %, 2 %, and 2.5 %. Following the 8-week feeding trial period, the shrimp endured a heat stress test lasting 1 h at a temperature of 38 °C. The results showed that the control group had a lower survival rate than those given BA. Interestingly, no mortality was observed in the group receiving 1.5 % BA supplementation. Heat stress had a negative impact on the activities of alkaline phosphatase (AKP) and acid phosphatase (ACP) in the control group. Still, these activities were increased in shrimp fed the BA diet. Similar variations were observed in AST and ALT fluctuations among the different groups. The levels of triglycerides (TG) and cholesterol (CHO) increased with high temperatures but were reduced in shrimp-supplemented BA. The activity of an antioxidant enzyme superoxide dismutase (SOD) increased with higher BA levels (P < 0.05). Moreover, the groups supplemented with 1.5 % BA exhibited a significant reduction in malondialdehyde (MDA) content (P < 0.05), suggesting the potential antioxidant properties of BA. The histology of the shrimp's hepatopancreas showed improvements in the groups given BA. Conversely, the BA significantly down-regulated the HSPs and up-regulated MnSOD transcript level in response to heat stress. The measured parameters determine the essential dietary requirement of BA for shrimp. Based on the results, the optimal level of BA for survival, antioxidant function, and immunity for shrimp under heat stress is 1.5 %.
Subject(s)
Animal Feed , Butyric Acid , Diet , Dietary Supplements , Heat-Shock Response , Hepatopancreas , Penaeidae , Animals , Penaeidae/immunology , Penaeidae/genetics , Penaeidae/physiology , Penaeidae/drug effects , Hepatopancreas/immunology , Hepatopancreas/drug effects , Diet/veterinary , Animal Feed/analysis , Dietary Supplements/analysis , Heat-Shock Response/drug effects , Butyric Acid/administration & dosage , Hot Temperature/adverse effects , Immunity, Innate/drug effects , Gene Expression/drug effects , Gene Expression/immunology , Random Allocation , Dose-Response Relationship, Drug , Gene Expression Regulation/drug effects , Gene Expression Regulation/immunologyABSTRACT
An oval to rod-shaped, Gram-stain-positive, strictly anaerobic bacterium, designated LFL-14T, was isolated from the faeces of a healthy Chinese woman. Cells of the strain were non-spore-forming, grew optimally at 37â°C (growth range 30-45â°C) and pH 7.0 (growth range 6.0-9.0) under anaerobic conditions in the liquid modified Gifu anaerobic medium (mGAM). The result of 16S rRNA gene-based analysis indicated that LFL-14T shared an identity of 94.7â0% with Eubacterium ventriosum ATCC 27560T, indicating LFL-14T represented a novel taxon. The results of genome-based analysis revealed that the average nucleotide identity (ANI), the digital DNA-DNA hybridisation (dDDH) and average amino acid identity (AAI) between LFL-14T and its phylogenetically closest neighbour, Eubacterium ventriosum ATCC 27560T, were 77.0â%, 24.6 and 70.9â%, respectively, indicating that LFL-14T represents a novel species of the genus Eubacterium. The genome size of LFL-14T was 2.92 Mbp and the DNA G+C content was 33.14 mol%. We analysed the distribution of the genome of LFL-14T in cohorts of healthy individuals, type 2 diabetes patients (T2D) and patients with non-alcoholic fatty liver disease (NAFLD). We found that its abundance was higher in the T2D cohort, but it had a low average abundance of less than 0.2â% in all three cohorts. The percentages of frequency of occurrence in the T2D, healthy and NAFLD cohorts were 48.87â%, 16.72â% and 13.10â% respectively. The major cellular fatty acids of LFL-14T were C16â:â0 (34.4â%), C17â:â0 2-OH (21.4â%) and C14â:â0 (11.7â%). Additionally, the strain contained diphosphatidylglycerol (DPG) and phosphatidylethanolamine (PE), as well as unidentified phospholipids and unidentified glycolipids. The glucose fermentation products of LFL-14T were acetate and butyrate. In summary, On the basis of its chemotaxonomic, phenotypic, phylogenetic and phylogenomic properties, strain LFL-14T (= CGMCC 1.18005T = KCTC 25580T) is identified as representing a novel species of the genus Eubacterium, for which the name Eubacterium album sp. nov. is proposed.
Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Eubacterium , Fatty Acids , Feces , Nucleic Acid Hybridization , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Humans , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Female , Eubacterium/genetics , Eubacterium/isolation & purification , Eubacterium/classification , Feces/microbiology , Butyrates/metabolism , Genome, Bacterial , China , AdultABSTRACT
The gut commensal bacteria Christensenellaceae species are negatively associated with many metabolic diseases, and have been seen as promising next-generation probiotics. However, the cultured Christensenellaceae strain resources were limited, and their beneficial mechanisms for improving metabolic diseases have yet to be explored. In this study, we developed a method that enabled the enrichment and cultivation of Christensenellaceae strains from fecal samples. Using this method, a collection of Christensenellaceae Gut Microbial Biobank (ChrisGMB) was established, composed of 87 strains and genomes that represent 14 species of 8 genera. Seven species were first described and the cultured Christensenellaceae resources have been significantly expanded at species and strain levels. Christensenella strains exerted different abilities in utilization of various complex polysaccharides and other carbon sources, exhibited host-adaptation capabilities such as acid tolerance and bile tolerance, produced a wide range of volatile probiotic metabolites and secondary bile acids. Cohort analyses demonstrated that Christensenellaceae and Christensenella were prevalent in various cohorts and the abundances were significantly reduced in T2D and OB cohorts. At species level, Christensenellaceae showed different changes among healthy and disease cohorts. C. faecalis, F. tenuis, L. tenuis, and Guo. tenuis significantly reduced in all the metabolic disease cohorts. The relative abundances of C. minuta, C. hongkongensis and C. massiliensis showed no significant change in NAFLD and ACVD. and C. tenuis and C. acetigenes showed no significant change in ACVD, and Q. tenuis and Geh. tenuis showed no significant change in NAFLD, when compared with the HC cohort. So far as we know, this is the largest collection of cultured resource and first exploration of Christensenellaceae prevalences and abundances at species level.
Subject(s)
Feces , Gastrointestinal Microbiome , Humans , Feces/microbiology , Clostridiales/genetics , Clostridiales/metabolism , Clostridiales/isolation & purification , Clostridiales/classification , Probiotics/metabolism , Metabolomics , Genomics , Male , Phylogeny , Female , Genome, BacterialABSTRACT
OBJECTIVES: This study explored the association between the Frailty Index (FI) and low back pain (LBP) in middle-aged and older Chinese adults. We hypothesised that a higher FI correlates with increased LBP prevalence. DESIGN: Cross-sectional analysis. SETTING: The study used data from the China Health and Retirement Longitudinal Study (CHARLS) across various regions of China. PARTICIPANTS: The analysis included 6375 participants aged 45 and above with complete LBP and FI data from the CHARLS for 2011, 2013 and 2015. We excluded individuals under 45, those with incomplete LBP data, participants with fewer than 30 health deficit items and those missing covariate data. OUTCOME MEASURES: We constructed an FI consisting of 35 health deficits. Logistic multivariable regression examined the relationship between FI and LBP, using threshold analysis to identify inflection points. Sensitivity analyses were performed to ensure the robustness of the findings. RESULTS: Of the participants, 27.2% reported LBP. A U-shaped association was observed between FI and LBP, with the highest quartile (Q4, FI ≥0.23) showing more than a twofold increased risk of LBP (OR=2.90, 95% CI: 2.45-3.42, p<0.001). Stratified analysis showed a significant association in participants under 60, particularly in the lowest FI quartile (OR=1.43, 95% CI: 1.14 to 1.79). Sensitivity analysis upheld the robustness of the primary results. CONCLUSIONS: The findings suggest a complex relationship between frailty and LBP, highlighting the need for early screening and tailored interventions to manage LBP in this demographic. Further research is necessary to understand the mechanisms of this association and to validate the findings through longitudinal studies.
Subject(s)
Frailty , Low Back Pain , Humans , Low Back Pain/epidemiology , Male , China/epidemiology , Female , Cross-Sectional Studies , Middle Aged , Aged , Longitudinal Studies , Frailty/epidemiology , Frailty/diagnosis , Prevalence , Logistic Models , Risk Factors , Aged, 80 and over , East Asian PeopleABSTRACT
Salvia miltiorrhiza Bunge (SM) is a widespread herbal therapy for myocardial ischemia (MI). Nevertheless, the therapeutic signaling networks of SM extract on MI is yet unknown. Emerging evidences suggested that alterations in cardiac metabolite influences host metabolism and accelerates MI progression. Herein, we employed an isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rat model to confirm the pharmacological effects of SM extract (0.8, 0.9, 1.8 g/kg/day) via assessment of the histopathological alterations that occur within the heart tissue and associated cytokines; we also examined the underlying SM extract-mediated signaling networks using untargeted metabolomics. The results indicated that 25 compounds with a relative content higher than 1 % in SM aqueous extract were identified using LC-MS/MS analysis, which included salvianolic acid B, lithospermic acid, salvianolic acid A, and caffeic acid as main components. An in vivo experiment showed that pretreatment with SM extract attenuated ISO-induced myocardial injury, shown as decreased myocardial ischemic size, transformed electrocardiographic, histopathological, and serum biochemical aberrations, reduced levels of proinflammatory cytokines, inhibited oxidative stress (OS), and reversed the trepidations of the cardiac tissue metabolic profiles. Metabolomics analysis shows that the levels of 24 differential metabolites (DMs) approached the same value as controls after SM extract therapy, which were primarily involved in histidine; alanine, aspartate, and glutamate; glycerophospholipid; and glycine, serine, and threonine metabolisms through metabolic pathway analysis. Correlation analysis demonstrated that the levels of modulatory effects of SM extract on the inflammation and OS were related to alterations in endogenous metabolites. Overall, SM extract demonstrated significant cardioprotective effects in an ISO-induced AMI rat model, alleviating myocardial injury, inflammation and oxidative stress, with metabolomics analysis indicating potential therapeutic pathways for myocardial ischemia.
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Bacterial ghosts (BGs) are hollow bacterial cell envelopes with intact cellular structures, presenting as promising candidates for various biotechnological and biomedical applications. However, the yield and productivity of BGs have encountered limitations, hindering their large-scale preparation and multi-faceted applications of BGs. Further optimization of BGs is needed for the commercial application of BG technology. In this study, we screened out the most effective lysis protein ID52-E-W4A among 13 mutants based on phage ID52 lysis protein E and optimized the liquid culture medium for preparing Escherichia coli Nissle 1917 (EcN). The results revealed a significantly higher lysis rate of ID52-E-W4A compared to that of ID52-E in the 2xYT medium. Furthermore, EcN BGs were cultivated in a fermenter, achieving an initial OD600 as high as 6.0 after optimization, indicating enhanced BG production. Moreover, the yield of ID52-E-W4A-induced BGs reached 67.0%, contrasting with only a 3.1% yield from φX174-E-induced BGs. The extended applicability of the lysis protein ID52-E-W4A was demonstrated through the preparation of Salmonella pullorum ghosts and Salmonella choleraesuis ghosts. Knocking out the molecular chaperone gene slyD and dnaJ revealed that ID52-mediated BGs could still undergo lysis. Conversely, overexpression of integral membrane enzyme gene mraY resulted in the loss of lysis activity for ID52-E, suggesting that the lysis protein ID52-E may no longer rely on SlyD or DnaJ to function, with MraY potentially being the target of ID52-E. This study introduces a novel approach utilizing ID52-E-W4A for recombinant expression, accelerating the BG formation and thereby enhancing BG yield and productivity.
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[This corrects the article DOI: 10.3389/fonc.2019.00033.].
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The negative coordination of growth hormone secretagogue receptor (GHS-R) and growth hormone-releasing hormone receptor (GHRH-R) involves in the repair processes of cellular injury. The allosteric U- or H-like modified GHRH dimer Grinodin and 2Y were comparatively evaluated in normal Kunming mice and hamster infertility models induced by CPA treatment. 1-3-9 µg of Grinodin or 2Y per hamster stem-cell-exhaustion model was subcutaneously administered once a week, respectively inducing 75-69-46 or 45-13-50 % of birth rates. In comparison, the similar mole of human menopausal gonadotropin (hMG) or human growth hormone (hGH) was administered once a day but caused just 25 or 20 % of birth rates. Grinodin induced more big ovarian follicles and corpora lutea than 2Y, hMG, hGH. The hMG-treated group was observed many distorted interstitial cells and more connective tissues and the hGH-treated group had few ovarian follicles. 2Y had a plasma lifetime of 21 days and higher GH release in mice, inducing lower birth rate and stronger individual specificity in reproduction as well as only promoting the proliferation of mesenchymal-stem-cells (MSCs) in the models. In comparison, Grinodin had a plasma lifetime of 30 days and much lower GH release in mice. It significantly promoted the proliferation and activation of ovarian MSCs together with the development of follicles in the models by increasing Ki67 and GHS-R expressions, and decreasing GHRH-R expression in a dose-dependent manner. However, the high GH and excessive estrogen levels in the models showed a dose-dependent reduction in fertility. Therefore, unlike 2Y, the low dose of Grinodin specifically shows low GHS-R and high GHRH-R expressions thus evades GH and estrogen release and improves functions of organs, resulting in an increase of fertility.
Subject(s)
Cell Proliferation , Mesenchymal Stem Cells , Ovary , Female , Animals , Mice , Cell Proliferation/drug effects , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Ovary/drug effects , Ovary/metabolism , Growth Hormone-Releasing Hormone/metabolism , Fertility/drug effects , Receptors, Neuropeptide/metabolism , Humans , Allosteric Regulation/drug effects , Receptors, Ghrelin/metabolism , Cricetinae , Receptors, Pituitary Hormone-Regulating Hormone/metabolism , DimerizationABSTRACT
Exhausted CD8+ T cells (Texs) are characterized by the expression of various inhibitory receptors (IRs), whereas the functional attributes of these co-expressed IRs remain limited. Here, we systematically characterized the diversity of IR co-expression patterns in Texs from both human oropharyngeal squamous cell carcinoma (OPSCC) tissues and syngeneic OPSCC model. Nearly 60% of the Texs population co-expressed two or more IRs, and the number of co-expressed IRs was positively associated with superior exhaustion and cytotoxicity phenotypes. In OPSCC patients, programmed cell death-1 (PD-1) blockade significantly enhanced PDCD1-based co-expression with other IR genes, whereas dual blockades of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) significantly upregulated CTLA4-based co-expression with other IR genes. Collectively, our findings demonstrate that highly diverse IR co-expression is a leading feature of Texs and represents their functional states, which might provide essential clues for the rational selection of immune checkpoint inhibitors in treating OPSCC.
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Influenza viruses cause epidemics and can cause pandemics with substantial morbidity with some mortality every year. Seasonal influenza vaccines have incomplete effectiveness and elicit a narrow antibody response that often does not protect against mutations occurring in influenza viruses. Thus, various vaccine approaches have been investigated to improve safety and efficacy. Here, we evaluate an mRNA influenza vaccine encoding hemagglutinin (HA) proteins in a BALB/c mouse model. The results show that mRNA vaccination elicits neutralizing and serum antibodies to each influenza virus strain contained in the current quadrivalent vaccine that is designed to protect against four different influenza viruses including two influenza A viruses (IAV) and two influenza B (IBV), as well as several antigenically distinct influenza virus strains in both hemagglutination inhibition assay (HAI) and virus neutralization assays. The quadrivalent mRNA vaccines had antibody titers comparable to the antibodies elicited by the monovalent vaccines to each tested virus regardless of dosage following an mRNA booster vaccine. Mice vaccinated with mRNA encoding an H1 HA had decreased weight loss and decreased lung viral titers compared to mice not vaccinated with an mRNA encoding an H1 HA. Overall, this study demonstrates the efficacy of mRNA-based seasonal influenza vaccines are their potential to replace both the currently available split-inactivated, and live-attenuated seasonal influenza vaccines.
Subject(s)
Influenza A virus , Influenza Vaccines , Influenza, Human , Orthomyxoviridae Infections , Animals , Mice , Humans , Hemagglutinins , mRNA Vaccines , Antibodies, Viral , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Influenza, Human/prevention & control , RNA, Messenger/geneticsABSTRACT
ETHNIC PHARMACOLOGICAL RELEVANCE: Anxiety or depression after percutaneous coronary intervention (PCI) is a common clinical disease. Currently, conventional pharmacotherapy primarily involves the administration of anxiolytic or antidepressant medications in conjunction with anticoagulants, antiplatelet agents, and other cardiovascular drugs. However, challenges such as drug dependence, adverse reactions and related concerns persist in the treatment of this disease. Numerous pertinent studies have demonstrated that Traditional Chinese Medicine (TCM) exhibits significant therapeutic efficacy and distinctive advantages in managing post-PCI anxiety or depression. AIM OF THIS REVIEW: This review attempted to summarize the characteristics of TCM for treating anxiety or depression after PCI, including single Chinese herbs, Chinese medicine monomers, compound TCM prescriptions, TCM patented drugs, and other TCM-related treatment methods, focusing on the analysis of the relevant mechanism of TCM treatment of this disease. METHODS: By searching the literature on treating anxiety or depression after PCI with TCM in PubMed, Web of Science, CNKI, and other relevant databases, this review focuses on the latest research progress of TCM treatment of this disease. RESULTS: In the treatment of anxiety or depression after PCI, TCM exerts significant pharmacological effects such as anti-inflammatory, antioxidant, anti-anxiety or anti-depression, cardiovascular and cerebrovascular protection, and neuroprotection, mainly by regulating the levels of related inflammatory factors, oxidative stress markers, neurotransmitter levels, and related signaling pathways. TCM has a good clinical effect in treating anxiety or depression after PCI with individualized treatment. CONCLUSIONS: TCM has terrific potential and good prospects in the treatment of anxiety or depression after PCI. The main direction of future exploration is the study of the mechanism related to Chinese medicine monomers and the large sample clinical study related to compound TCM prescriptions.
Subject(s)
Drugs, Chinese Herbal , Percutaneous Coronary Intervention , Medicine, Chinese Traditional/methods , Drugs, Chinese Herbal/adverse effects , Percutaneous Coronary Intervention/adverse effects , Depression/drug therapy , Anxiety/drug therapyABSTRACT
Statement of problem: There is currently no consensus on the relationship between maxillary anterior teeth and different facial anthropometric measurements. Additionally, whether these relationships vary by age and sex remains unreported. Purpose: This clinical study aimed to investigate the relationship between the intercanine distance (ICaD) and intercanthal distance (ICD), interpupillary distance (IPD), interalar width (IAW), and intercommissural width (ICW), and to compare whether these relationships differ between different age and sex populations. Material and methods: Participants (n = 409) were enrolled according to the inclusion criteria, and their standardized digital images were taken to measure facial and oral segments through an image processing program. The differences between ICaD and four facial measurements and the sexual differences for all measurements were compared using the 1-sample t-test. The differences among different age groups for all measurements were compared using the one-way analysis of variance (ANOVA) test, and a least significant difference (LSD) test was used for multiple comparisons. The association between ICaD and the four facial measurements was evaluated using Pearson correlation analysis. The correlation between ICaD and four facial measurements was evaluated using linear regression. Differences in regression equations among the subgroups were evaluated through subgroup regression analysis and the significance test of the difference between the two regression coefficients. Tests of significance were two-sided, with alpha level of 0.05. The reliability of the results was evaluated by calculating intraclass correlation coefficients. Results: The ICD, IPD, ICW, and IAW significantly differed from the ICaD in both sexes (P < 0.01). All measurements were significantly greater in men than in women (P < 0.01). The differences among the age groups were statistically significant for all measurements except IPD (P < 0.05). A significant positive correlation was found between all facial measurements (r = 0.258 [ICD], r = 0.334 [IPD], r = 0.389 [ICW], and r = 0.393 [IAW]) and the ICaD in both sexes. The highest correlation was found between ICW(r = 0.345) and ICAD in men and IAW (r = 0.285) and ICAD in women. Except for the 20-29 and 50-59 age groups, the mathematical equations of ICaD and facial anthropometric measurements differed among the other age groups and sexes. Conclusions: ICD, IPD, ICW, and IAW cannot be directly used to determine ICaD in both sexes. Nevertheless, when observed from the frontal aspect, by the use of digital images, all facial measurements correlated to the intercanine distance, with a high probability. The mathematical formulae combined with facial anthropological measurements can help ensure the combined width of the six maxillary anterior teeth, but the effects of sex and age differences should be considered.