ABSTRACT
To investigate the impact and potential mechanisms of extracts from different parts of Liparis nervosa on neuroinflammation by lipopolysaccharide(LPS)-induced BV-2 microglial cells. The materials of L. nervosa were subjected to crushing, ethanol extraction, and concentration to obtain an alcohol extract. Subsequently, the extract was further extracted to obtain petroleum ether extract, ethyl acetate extract, N-butanol extract, and aqueous phase extract. The ethyl acetate extract was separated into distillate(1)-(6)using D101 macroporous resin column chromatography. The experiment was divided into control group, LPS model group, L. nervosa extract group, and LPS + L. nervosa group. LPS was utilized to induce a neuroinflammatory cell model in BV-2 microglial cells. The Griess test was utilized for detecting the production of nitric oxide(NO) in the cell supernatant. Cell viability was detected by MTT assay. The release of interleukin-6(IL-6) and tumor necrosis factor alpha(TNF-α) in the cell supernatant was quantified using ELISA.RT-qPCR was utilized to assess the m RNA levels of pro-inflammatory cytokines inducible nitric oxide synthase(iNOS), cyclooxygenase-2(COX-2), interleukin( IL)-6, IL-1ß, and TNF-α. The protein expression of i NOS, COX-2, nuclear factor kappa-B p65(p65), p-p65, extracellular signal-regulated kinase(ERK), p-ERK, c-jun N-terminal kinase(JNK), p-JNK, p38 mitogen-activated protein kinase(p38), and p-p38 MAPK(p-p38) were also evaluated by Western blot. The chemical composition of active substances in L. nervosa was analyzed using the UHPLC-Q-Exactive Orbitrap technology and literature comparison. Our findings indicate that extracts from different parts of L. nervosa exhibit a significant reduction in the release of NO from LPS-induced BV-2 microglial cells.Specifically, the ethyl acetate extract demonstrates the most notable inhibitory effect without causing cell toxicity. Additionally, the distillate(6) extracted from the ethyl acetate exhibits a reduction in the m RNA and protein levels of i NOS, COX-2, IL-6, IL-1ß, and TNF-α in a dose-dependent manner, and it inhibits the protein expression of p-p65, p-ERK, p-p38, and p-JNK in LPS-induced BV-2 microglial cells. A total of 79 compounds in the distillate(6) were identified by mass spectrometry, including 12 confirmed compounds with anti-inflammatory effects. This study confirmed the remarkable efficacy of L. nervosa extract in the treatment of neuroinflammation, which may be achieved through the inhibition of NF-κB and MAPK signaling pathways.
Subject(s)
Lipopolysaccharides , Microglia , Microglia/drug effects , Microglia/metabolism , Animals , Mice , Nitric Oxide/metabolism , Neuroinflammatory Diseases/drug therapy , Cell Survival/drug effects , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Cell Line , Interleukin-6/genetics , Interleukin-6/metabolism , Plant Extracts/pharmacology , Plant Extracts/chemistryABSTRACT
BACKGROUND: Anshen Buxin Liuwei pill (ABLP) is a Mongolian medicinal formula that is composed of six medicinal materials: the Mongolian medicine Bos taurus domesticus Gmelin, Choerospondias axillaris (Roxb.) Burtt et Hill, Myristica fragrans Houtt., Eugenia caryophµllata Thunb., Aucklandia lappa Decne., and Liqui dambar formosana Hance. ABLP is considered to have a therapeutic effect on symptoms such as coronary heart disease, angina pectoris, arrhythmia, depression and irritability, palpitation, and shortness of breath. METHODS: H9c2 cardiomyocytes were used to construct a hypoxia/reoxygenation (HR) injury model. CCK-8 assay and Annexin V-FITC cell apoptosis assays were used for cell viability and cell apoptosis determination. The LDH, SOD, MDA, CAT, CK, GSH-Px, Na+-K+-ATPase, and Ca2+-ATPase activities in cells were determined to assess the protective effects of ABLP. The mRNA levels of Sirtuin3 (Sirt3) and Cytochrome C (Cytc) in H9c2 cells were determined by quantitative real-time PCR. RESULTS: The results indicate that HR-treated cells began to shrink from the spindle in an irregular shape with some floated in the medium. By increasing the therapeutic dose of ABLP (5, 25, and 50 µg/mL), the cells gradually reconverted in a concentration-dependent manner. The release of CK in HR-treated cells was significantly increased, indicating that ABLP exerts a protective effect in H9c2 cells against HR injury and can improve mitochondrial energy metabolism and mitochondrial function integrity. The present study scrutinized the cardioprotective effects of ABLP against HR-induced H9c2 cell injury through antioxidant and mitochondrial pathways. CONCLUSIONS: ABLP could be a promising therapeutic drug for the treatment of myocardial ischemic cardiovascular disease. The results will provide reasonable information for the clinical use of ABLP.
Subject(s)
Medicine, East Asian Traditional/methods , Myocardial Reperfusion Injury/prevention & control , Myocytes, Cardiac/metabolism , Animals , Apoptosis/drug effects , Cell Hypoxia/drug effects , Cell Line , Cell Survival/drug effects , Cytochromes c/metabolism , Hypoxia/metabolism , Mitochondria/metabolism , Myocardial Reperfusion Injury/drug therapy , Myocytes, Cardiac/drug effects , Oxidative Stress/drug effects , Rats , Sirtuin 3/metabolismABSTRACT
PURPOSE: Oocyte death is a severe clinical phenotype that causes female infertility and recurrent in vitro fertilization and intracytoplasmic sperm injection failure. We aimed to identify pathogenic variants in a female infertility patient with oocyte death phenotype. METHODS: Sanger sequencing was performed to screen PANX1 variants in the affected patient. Western blot analysis was used to check the effect of the variant on PANX1 glycosylation pattern in vitro. RESULTS: We identified a novel PANX1 variant (NM_015368.4 c.86G > A, (p. Arg29Gln)) associated with the phenotype of oocyte death in a non-consanguineous family. This variant displayed an autosomal dominant inheritance pattern with reduced penetrance. Western blot analysis confirmed that the missense mutation of PANX1 (c.86G > A) altered the glycosylation pattern in HeLa cells. Moreover, the mutation effects on the function of PANX1 were weaker than recently reported variants. CONCLUSION: Our findings expand the inheritance pattern of PANX1 variants to an autosomal dominant mode with reduced penetrance and enrich the variational spectrum of PANX1. These results help us to better understand the genetic basis of female infertility with oocyte death.
Subject(s)
Infertility, Female , Connexins/genetics , Female , HeLa Cells , Heterozygote , Humans , Infertility, Female/pathology , Male , Nerve Tissue Proteins/genetics , Oocytes/pathology , SemenABSTRACT
Background: Pneumocephalus is a common finding after burr-hole drainage of chronic subdural hematoma (CSDH). Its effects have not been specifically studied.Methods: A retrospective analysis was performed in 140 patients with CSDH with single burr-hole drainage. The pre- and postoperative volumes of intracranial hematoma and the postoperative volume of pneumocephalus were calculated and analyzed with their relationships with Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) scores.Results: The preoperative hematoma volume and the patient ages are positively correlated with the 1-day postoperative pneumocephalus volume (p < 0.001, p < 0.01). There is no correlation between postoperative pneumocephalus volume and GCS/GOS scores (p > 0.05) and there is no difference of GCS/GOS scores or CSDH recurrence rate between patients with and without pneumocephalus (p > 0.05). The age and the volume of 1-day postoperative pneumocephalus are positively correlated with the absorbing rate of pneumocephalus (p < 0.01, p < 0.001).Conclusions: The pneumocephalus at a certain range has no effect on the prognosis of patients with CSDH and requires no specific intervention due to its self-absorbing capacity in the normal progress after surgery.HighlightsNo correlation between postoperative pneumocephalus volume and GCS/GOS scores.No difference of GCS/GOS or recurrence between patients with pneumocephalus or not.Pneumocephalus at certain range has no effect on the prognosis of patients.
Subject(s)
Hematoma, Subdural, Chronic , Pneumocephalus , Drainage , Hematoma, Subdural, Chronic/surgery , Humans , Patients , Recurrence , Retrospective Studies , Treatment Outcome , TrephiningABSTRACT
BACKGROUND: Although in vitro culture system has been optimized in the past few decades, the problem of few or no high quality embryos has been still not completely solved. Accordingly, fully understanding the regulatory mechanism of pre-implantation embryonic development would be beneficial to further optimize the in vitro embryo culture system. Recent studies have found the expression of c-kit in mouse embryo and its promotion effects on mouse embryonic development. However, it is unclear the expression, the role and the related molecular regulatory mechanism of c-kit in human pre-implantation embryo development. Therefore, the present study is to determine whether c-kit is expressed in human pre-implantation embryos, and to investigate the possible regulatory mechanism of c-kit signaling in the process of embryonic development. METHODS: The present study includes human immature oocytes and three pronucleus (3PN) embryos collected from 768 women (28-32 ages) undergoing IVF, and normal 2PN embryos collected from ICR mice. Samples were distributed randomly into three different experimental groups: SCF group: G-1™ (medium for culture of embryos from the pro-nucleate stage to day 3) or G-2™ (medium for culture of embryos from day3 to blastocyst stage) + HSA (Human serum album) solution + rhSCF; SCF + imanitib (c-kit inhibitor) group: G-1™ or G-2™ + HSA solution + rhSCF + imanitib; SCF + U0126 (MEK/ERK inhibitor) group: G-1™ or G-2™ + HSA solution + rhSCF + U0126; Control group: G-1™ or G-2™ + HSA solution + PBS; The rate of good quality embryos at day 3, blastulation at day 6 and good quality blastulation at day 6 were analysis. RT-PCR, western blot and immunofluorescence staining were applied to detect the target genes and proteins in samples collected from human or mice, respectively. RESULTS: c-kit was expressed ubiquitously in all human immature oocytes, 3PN embryos and 3PN blastocysts. In the experiment of human 3PN embryos, compared with other groups, SCF group showed obviously higher rate of good quality at day 3, better rate of blastocyst formation at day 6 and higher rate of good quality blastocyst formation at day 6. Furthermore, we observed a higher ETV5 expression in SCF group than that in other groups. Similar results were also found in animal experiment. Interestingly, we also found a higher phosphorylation level of MEK/ERK signal molecule in mice embryos from SCF group than those from other groups. Moreover, inhibition of MEK/ERK signaling would remarkably impeded the mice embryonic development, which might be due to the reduced ETV5 expression. CONCLUSIONS: The present study firstly revealed that c-kit signaling might promote the human pre-implantation embryonic development and blastocyst formation by up-regulating the expression of ETV5 via MEK/ERK pathway. Our findings provide a new idea for optimizing the in vitro embryo culture condition during ART program, which is beneficial to obtain high quality embryos for infertile patients.
Subject(s)
Blastocyst/metabolism , Embryo Transfer/methods , Embryonic Development/genetics , Gene Expression Regulation, Developmental , Proto-Oncogene Proteins c-kit/genetics , Signal Transduction/genetics , Adult , Animals , DNA-Binding Proteins , Embryo Culture Techniques/methods , Embryo Implantation/genetics , Female , Humans , Mice, Inbred ICR , Pregnancy , Proto-Oncogene Proteins c-kit/metabolism , Transcription FactorsABSTRACT
OBJECTIVE: To study the morphological characteristics of femurs of adult human and 11 kinds of adult animals from cattle, horses, pigs, goats, sheep, dogs, cats, rabbits, geese, ducks, chickens, and to establish an effective species identification method among various species. METHODS: The 4 cm mid-diaphyseal segment of the femur from adult human (older than 20 years old) at autopsy was obtained. Addi-tionally, the 4 cm ones from 11 kinds of adult animals were obtained. After decalcification, all femurs were made into slices, and then were observed by optical microscope. The 25 indexes were selected and analyzed by step discriminant analysis according to differences between human and mammal, human and poultry, and human and 11 kinds of animals. RESULTS: The histological structure of bone mineral density of middle part of femur had obvious characteristics among the species. And the morphology and number of osteon showed the trend of obvious biological evolution. There were 11 indexes with significant differences between human and 11 kinds of animals to establish some mathematical models to discriminate all species. The correct discrimination rate was 96.3% between human and mammal. The correct discrimination rate was up to 100% between human and poultry, and was 89.4% among human, mammal and poultry. CONCLUSION: The mathematical models have good correct discrimination rate among human and the other animals, which could be applied in the practical species identification cases.
Subject(s)
Femur/ultrastructure , Haversian System/ultrastructure , Adult , Animals , Autopsy , Bone Density , Cadaver , Cats , Cattle , Chickens , Discriminant Analysis , Dogs , Forensic Anthropology , Horses , Humans , Sheep , Species Specificity , SwineABSTRACT
OBJECTIVES: The CC chemokine ligand-20 (CCL-20)/macrophage inflammatory protein-3α has been seen as one of the most important chemokines and played a key role in atherogenesis, but the mechanism that underlies the regulation of CCL-20 has not been established clearly yet. The aim of this study was to investigate the influence of salvianolic acid A (SAA) on the expression of CCL-20 in macrophages and ApoE-deficient (ApoE) mice. METHODS: The expression of CCL-20 was detected both at protein and messenger RNA levels in RAW264.7 cells. We validated the result in ApoE mice that were intraperitoneally injected with SAA. Phosphorylation of p38 mitogen-activated protein kinase was detected with Western blot, and inhibitor of p38 was used to investigate the mechanism of regulation of CCL-20. Hematoxylin and eosin and Oil-Red-O staining were used to evaluate the atherosclerotic lesions and lipid accumulation in ApoE mice. Immunohistochemical analysis was used to detect the expressions of CCL-20 and CCR6 in the atherosclerotic lesions. Immunofluorescent analysis was used to certify the origination of CCL-20. RESULTS: Recombinant tumor necrosis factor-α (TNF-α) upregulated CCL-20 production in dose- and time-dependent manners in RAW264.7 cells. The activity of TNF-α-induced CCL-20 production seemed to be significantly suppressed by SAA. Using p38 mitogen-activated protein kinase inhibitor, we found that p38 mediated the effects of TNF-α- and SAA-induced CCL-20 expression changes. In addition, immunohistochemical analysis of aortic root of ApoE mice also demonstrated that the expressions of CCL-20 and CCR6 were both downregulated significantly with SAA treatment. Furthermore, treatment of SAA inhibited the progression of the atherosclerotic plaques and lipid accumulation. CONCLUSIONS: These results demonstrate that TNF-α increased but SAA suppressed CCL-20 production significantly via a novel mechanism.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Atherosclerosis/drug therapy , Caffeic Acids/pharmacology , Chemokine CCL20/genetics , Lactates/pharmacology , Macrophages/drug effects , Tumor Necrosis Factor-alpha/pharmacology , Animals , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Atherosclerosis/metabolism , Atherosclerosis/pathology , Blotting, Western , Cell Line , Chemokine CCL20/immunology , Disease Models, Animal , Dose-Response Relationship, Drug , Lipid Metabolism/drug effects , Macrophages/immunology , Mice, Inbred C57BL , Mice, Knockout , Real-Time Polymerase Chain Reaction , Recombinant Proteins , Sinus of Valsalva/drug effects , Sinus of Valsalva/metabolism , Sinus of Valsalva/pathology , Time Factors , Tumor Necrosis Factor-alpha/immunology , Up-RegulationABSTRACT
A plot experiment was carried out to assess the applicability of soil conditioners on Cd-polluted acidic paddy fields. The effects of five soil conditioners[Tianxiang 1 Hao (TX1), limestone (Li), silicon fertilizer, Nuodikang (NDK), and calcium magnesium phosphate fertilizer (CaMg-P)] on Cd accumulation and transport between contaminated soil and rice plants and rice yield on the land were analyzed. The results showed that compared with that under the control, other tested methods increased soil pH by 0.41-0.68 units and decreased available Cd content in the soil by 11.2%-39.7%. The difference between Li- and NDK-treated soil available Cd reached a significant level (P < 0.05). â¡ Compared with that in the blank control, the application of soil conditioner could significantly reduce the total amount of Cd in rice, and the Cd content in roots, other leaves, rachises, chaffs, and brown rice were significantly lower than those in the CK treatment (P < 0.05). The Cd translation factor between various sites was shown as TFroots-other nodes > TFroots-first nodes > TFroots-rachises > TFroots-chaffs ≈ TFroots-flag leaves > TFroots-brown rice. The Cd content of brown rice met the national safety standard (0.2 mg·kg-1), in which the TX1, Li, and CaMg-P treatments showed significant Cd reduction effects, and ω(Cd) was 0.097, 0.094, and 0.134 mg·kg-1, respectively. ⢠The application of soil conditioner could increase the yield by 9.9%-35.8%, and the yield of the CaMg-P and TX1 treatments was significantly higher than that of other treatments (P < 0.05). ⣠Correlation analysis showed that the Cd content in brown rice was significantly positively correlated with available Cd content in soil, available Fe content in soil, and available phosphorus but negatively correlated with soil pH. In summary, TX1 and CaMg-P are recommended to be applied in farmland lightly polluted by the heavy metal Cd to ensure the safety of agricultural products.
Subject(s)
Oryza , Phosphates , Soil Pollutants , Soil/chemistry , Cadmium/analysis , Oryza/chemistry , Fertilizers/analysis , Soil Pollutants/analysis , Calcium CarbonateABSTRACT
OBJECTIVE: To evaluate the prognostic factors and survival outcomes of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix (NECC). METHODS: This multicenter, retrospective study involved 98 cervical cancer patients with stage IA2-IIA2 and IIIC1/2p high-grade NECC. We divided the patients into two groups based on histology: the pure and mixed groups. All clinicopathologic variables were retrospectively evaluated. Cox regression and Kaplan-Meier methods were used for analysis. RESULTS: In our study, 60 patients were in the pure group and 38 patients were in the mixed group. Cox multivariate analysis showed that mixed histology was a protective factor impacting overall survival (OS) (P = 0.026) and progression free survival (PFS) (P = 0.018) in surgically treated high-grade NECC. Conversely, survival outcomes were negatively impacted by ovarian preservation (OS: HR, 20.84; 95% CI: 5.02-86.57, P < 0.001), age >45 years (OS: HR, 4.50; 95% CI: 1.0-18.83, P = 0.039), tumor size >4 cm (OS: HR, 6.23; 95% CI: 2.34-16.61, P < 0.001), parity >3 (OS: HR, 4.50; 95% CI: 1.02-19.91, P = 0.048), and perineural invasion (OS: HR, 5.21; 95% CI: 1.20-22.53, P = 0.027). Kaplan-Meier survival curves revealed notable differences in histologic type (OS: P = 0.045; PFS: P = 0.024), chemotherapy (OS: P = 0.0056; PFS: P = 0.0041), ovarian preservation (OS: P = 0.00031; PFS: P = 0.0023), uterine invasion (OS: P < 0.0001; PFS: P < 0.0001), and depth of stromal invasion (OS: P = 0.043; PFS: P = 0.022). CONCLUSION: Patients with mixed histologic types who undergo surgery for high-grade NECC have a better prognosis. Meanwhile, ovarian preservation, tumor size >4 cm, parity >3, age >45 years and perineural invasion were poor prognostic predictors. Therefore, patients with high-risk factors should be considered in clinical practice.
ABSTRACT
Background: Mental health disorders in patients with multi-drug or rifampicin-resistant tuberculosis (MDR/RR-TB) receive consistent attention. Anxiety and depression can manifest and may impact disease progression in patients with MDR/RR-TB. Given the heightened stressors resulting from the COVID-19 pandemic, this scenario is even more concerning. Objective: To evaluate the prevalence of and risk factors associated with anxiety and depression among patients with MDR/RR-TB in southern China. Methods: A facility-based cross-sectional study was undertaken at Guangzhou Chest Hospital in southern China, encompassing a cohort of 219 patients undergoing outpatient and inpatient treatment for MDR/RR-TB. Anxiety and depressive symptoms were assessed using the 7-Item Generalized Anxiety Disorder (GAD-7) scale and Patient Health Questionnaire-9 (PHQ-9). The ramifications of anxiety and depression were examined using univariate and multivariate logistic regression analyses, with odds ratios (ORs) and age- and sex-adjusted ORs (AORs) employed to quantify their influence. All data underwent statistical analysis using SPSS 25.0, with statistical significance established at P < 0.05. Results: Two hundred and nineteen individuals with MDR/RR-TB were included in the study. The prevalence of anxiety and depression was 57.53% (n = 126) and 65.75% (n = 144), respectively, with 33.3% (n = 73) of the participants experiencing both conditions simultaneously. Multivariate logistic regression analysis revealed that an age of 20-40 years [anxiety AOR = 3.021, 95% confidence interval (CI): 1.240-7.360; depression AOR = 3.538, 95% CI: 1.219-10.268], disease stigma (anxiety AOR = 10.613, 95% CI: 2.966-37.975; depression AOR = 4.514, 95% CI: 2.051-10.108) and poor physical health (anxiety AOR = 7.636, 95% CI: 2.938-19.844; depression AOR = 6.190, 95% CI: 2.468-15.529) were significant risk factors for moderate levels of anxiety and depression. Conclusions: We found that individuals with MDR/RR-TB had an elevated risk of anxiety and depression. To decrease the likelihood of unfavorable treatment outcomes, it is imperative to carefully monitor the psychological wellbeing of patients with MDR/RR-TB and promptly address any detrimental psychiatric conditions.
Subject(s)
Rifampin , Tuberculosis, Multidrug-Resistant , Humans , Young Adult , Adult , Rifampin/therapeutic use , Depression/epidemiology , Prevalence , Cross-Sectional Studies , Pandemics , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/drug therapy , Risk Factors , Anxiety/epidemiology , Anxiety Disorders/epidemiologyABSTRACT
In China, Russia, Mongolia, Japan, North Korea, and Mexico, Sedum aizoon L. (S. aizoon) is used as an edible plant. Up to now, over 234 metabolites, including phenolic acids, flavonoids, triterpenes, phytosterols, and alkaloids, among others, have been identified. In addition to its antioxidant, anti-inflammatory, anti-fatigue, antimicrobial, anti-cancer, and hemostatic activities, S. aizoon is used for the treatment of cardiovascular disease. This paper provides an overview of the history, botany, nutritional value, traditional use, phytochemistry, pharmacology, toxicology, and quality control of S. aizoon.
ABSTRACT
It is recognized that PCOS patients are often accompanied with aberrant follicular development, which is an important factor leading to infertility in patients. However, the relevant regulatory mechanisms of abnormal follicular development are not well understood. In the present study, by collecting human ovarian granulosa cells (GCs) from PCOS patients who underwent in vitro fertilization (IVF), we found that the proliferation ability of GCs in PCOS patients was significantly reduced. Surprisingly, PATL2 and adrenomedullin 2 (ADM2) were obviously decreased in the GCs of PCOS patients. To further explore the potential roles of PATL2 and ADM2 on GC, we transfected PATL2 siRNA into KGN cells to knock down the expression of PATL2. The results showed that the growth of GCs remarkably repressed after knocking down the PATL2, and ADM2 expression was also weakened. Subsequently, to study the relationship between PATL2 and ADM2, we constructed PATL2 mutant plasmid lacking the PAT construct and transfected it into KGN cells. The cells showed the normal PATL2 expression, but attenuated ADM2 expression and impaired proliferative ability of GCs. Finally, the rat PCOS model experiments further confirmed our findings in KGN cells. In conclusion, our study suggests that PATL2 promoted the proliferation of ovarian GCs by stabilizing the expression of ADM2 through "PAT" structure, which is beneficial to follicular development, whereas, in the ovary with polycystic lesions, reduction of PATL2 could result in the decreased expression of ADM2, subsequently weakened the proliferation ability of GCs and finally led to the occurrence of aberrant follicles.
Subject(s)
Peptide Hormones , Polycystic Ovary Syndrome , Animals , Female , Humans , Rats , Cell Proliferation , Granulosa Cells/metabolism , Peptide Hormones/metabolism , Polycystic Ovary Syndrome/metabolismABSTRACT
BACKGROUND: Polypoidal choroidal vasculopathy (PCV) is a hemorrhagic fundus disease that can lead to permanent vision loss. Predicting the treatment response to anti-VEGF monotherapy in PCV is consistently challenging. We aimed to conduct a prospective multicenter study to explore and identify the imaging biomarkers for predicting the anti-VEGF treatment response in PCV patients, establish predictive model, and undergo multicenter validation. METHODS: This prospective multicenter study utilized clinical characteristics and images of treatment naïve PCV patients from 15 ophthalmic centers nationwide to screen biomarkers, develop model, and validate its performance. Patients from Peking Union Medical College Hospital were randomly divided into a training set and an internal validation set. A nomogram was established by univariate, LASSO regression, and multivariate regression analysis. Patients from the other 14 centers served as an external test set. Area under the curve (AUC), sensitivity, specificity, and accuracy were calculated. Decision curve analysis (DCA) and clinical impact curve (CIC) were utilized to evaluate the practical utility in clinical decision-making. FINDINGS: The eye distribution for the training set, internal validation set, and external test set were 66, 31, and 71, respectively. The 'Good responder' exhibited a thinner subfoveal choroidal thickness (SFCT) (230.67 ± 61.96 vs. 314.42 ± 88.00 µm, p < 0.001), lower choroidal vascularity index (CVI) (0.31 ± 0.08 vs. 0.36 ± 0.05, p = 0.006), fewer choroidal vascular hyperpermeability (CVH) (31.0 vs. 62.2%, p = 0.012), and more intraretinal fluid (IRF) (58.6 vs. 29.7%, p = 0.018). SFCT (OR 0.990; 95% CI 0.981-0.999; p = 0.033) and CVI (OR 0.844; 95% CI 0.732-0.971; p = 0.018) were ultimately included as the optimal predictive biomarkers and presented in the form of a nomogram. The model demonstrated AUC of 0.837 (95% CI 0.738-0.936), 0.891 (95% CI 0.765-1.000), and 0.901 (95% CI 0.824-0.978) for predicting 'Good responder' in the training set, internal validation set, and external test set, respectively, with excellent sensitivity, specificity, and practical utility. INTERPRETATION: Thinner SFCT and lower CVI can serve as imaging biomarkers for predicting good treatment response to anti-VEGF monotherapy in PCV patients. The nomogram based on these biomarkers exhibited satisfactory performances.
Subject(s)
Angiogenesis Inhibitors , Biomarkers , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A , Humans , Male , Female , Prospective Studies , Aged , Middle Aged , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Choroid/blood supply , Choroid/diagnostic imaging , Choroidal Neovascularization/drug therapy , Choroidal Neovascularization/diagnostic imaging , Treatment Outcome , Nomograms , Polyps/drug therapy , Polyps/diagnostic imaging , Polyps/diagnosis , Fluorescein Angiography/methods , Choroid Diseases/drug therapy , Choroid Diseases/diagnostic imaging , Choroid Diseases/diagnosis , Polypoidal Choroidal VasculopathyABSTRACT
OBJECTIVE: To investigate the epidemic characteristics and pathogenic spectrum of community acquired pneumonia (CAP) in Guangzhou from 2009 to 2012. METHOD: 14 major comprehensive hospitals were selected from 11 districts as sentinel hospitals for CAP cases surveillance, including 18 982 223 in total during the 4 years. The characteristics of pathogenic spectrum of CAP were stratified and analyzed by year, age and season. RESULTS: 18 982 223 cases were included in the surveillance from year 2009 to 2012, in which 56 618 cases were CAP. The number of CAP cases increased from 8677 in year 2009 to 19 947 in year 2012 in Guangzhou; while the percentage of visits for CAP raised from 0.22% (8677/3 893 800) to 0.41% (19 947/4 839 766). The difference showed statistical significance (χ(2) = 2693.00, P < 0.05). Among the hospitalized CAP cases, 66.05% (10 954/16 585) were aged ≤ 5 years old or > 66 years old. The percentage of cases infected by a single pathogen was 88.11% (14 613/16 585), while co-infected cases accounted for 4.17% (691/16 585). Bacteria accounted for the largest proportion of 65.25% (10 821/16 585) as a single pathogen, followed by mycoplasma 13.54% (2245/16 585), virus 9.01% (1494/16 585) and chlamydia 0.32% (53/16 585). The proportion of virus infection was increasing from 4.74% to 11.64%. The difference showed statistical significance (χ(2) = 135.32, P < 0.05). Bacteria infection was the leading causes for CAP cases in all age groups; however the percentage increased with the increasing of ages. The rate of bacterial infection was increased from 48.35% (2993/6191) among children aged ≤ 5 years old to 81.31% (3873/4763) among adults aged over 65 years (χ(2) = 1632.00, P < 0.05). The rate of atypical pathogens (mycoplasma, chlamydia) for children ( ≤ 15 years old) (25.99%, 1805/6945) was higher than that for adults aged ≥ 16 years old (5.12%, 494/9640) (χ(2) = 2.11, P < 0.05). The effect from season on the pathogenic spectrum was not observed.433 hospitalized CAP cases were dead from 2009 to 2012. Case fatality rate was highest among people aged over 65 years old (4.70%, 224/4763) and lowest among children aged between 6 to 15 years old (0.27%, 2/754). CONCLUSION: The incidence of community acquired pneumonia was rising in Guangzhou from 2009 to 2012. Bacteria was the dominant pathogen. Children and old people were the high-risk population of community acquired pneumonia; while co-infection was still at low level.
Subject(s)
Community-Acquired Infections/epidemiology , Pneumonia/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , China/epidemiology , Community-Acquired Infections/microbiology , Female , Humans , Infant , Male , Middle Aged , Pneumonia/microbiology , Sentinel Surveillance , Young AdultABSTRACT
This article explores aggregative games in a network of general linear systems subject to external disturbances. To deal with external disturbances, distributed strategy-updating rules based on the internal model are proposed for the case with perfect and imperfect information, respectively. Different from the existing algorithms based on gradient dynamics, by introducing the integral of the gradient of cost functions on the basis of the passivity theory, the rules are proposed to force the strategies of all agents to evolve to the Nash equilibrium, regardless of the effect of disturbances. The convergence of the two strategy-updating rules is analyzed via the Lyapunov stability theory, passivity theory, and singular perturbation theory. Simulations are performed to illustrate the effectiveness of the proposed methods.
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Background and objective: Cerebrocardiac syndrome (CCS) is a severe complication of severe traumatic brain injury (sTBI) that carries high mortality and disability rates. Early identification of CCS poses a significant clinical challenge. The main objective of this study was to investigate potential risk factors associated with the development of secondary CCS in patients with sTBI. It was hypothesized that elevated right heart Tei index (TI), lower Glasgow Coma Scale (GCS) scores, and elevated cardiac troponin-I (cTnI) levels would independently contribute to the occurrence of CCS in sTBI patients. Methods: A retrospective cohort study was conducted to identify risk factors for CCS secondary to sTBI. One hundred and fifty-five patients were enrolled with sTBI admitted to the hospital between January 2016 and December 2020 and divided them into a CCS group (n = 75) and a non-CCS group (n = 80) based on the presence of CCS. This study involved the analysis and comparison of clinical data from two patient groups, encompassing demographic characteristics, peripheral oxygen saturation (SPO2), neuron-specific enolase (NSE), cardiac troponin-I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), optic nerve sheath diameter (ONSD), cardiac ultrasound, acute physiology and chronic health evaluation (APACHE II) scores, and GCS scores and so on. Multivariate logistic regression was employed to identify independent risk factors for CCS, and receiver operating characteristic (ROC) curves were used to assess their predictive value for CCS secondary to sTBI. Results: The study revealed that 48.4% of sTBI patients developed secondary CCS. In the multivariate analysis model 1 that does not include NT-proBNP and cTnI, ONSD (OR = 2.582, 95% CI: 1.054-6.327, P = 0.038), right heart Tei index (OR = 2.81, 95% CI: 1.288-6.129, P = 0.009), and GCS (OR = 0.212, 95% CI: 0.086-0.521, P = 0.001) were independent risk factors for secondary CCS in sTBI patients. In multivariate analysis model 2 that includes NT-proBNP and cTnI, cTnI (OR = 27.711, 95%CI: 3.086-248.795, P = 0.003), right heart Tei index (OR = 2.736, 95% CI: 1.056-7.091, P = 0.038), and GCS (OR = 0.147, 95% CI: 0.045-0.481, P = 0.002) were independent risk factors for secondary CCS in sTBI patients. The area under the ROC curve for ONSD, Tei index, GCS, and cTnI were 0.596, 0.613, 0.635, and 0.881, respectively. ONSD exhibited a positive predictive value (PPV) of 0.704 and a negative predictive value (NPV) of 0.634. The Tei index demonstrated a PPV of 0.624 and an NPV of 0.726, while GCS had a PPV of 0.644 and an NPV of 0.815. On the other hand, cTnI exhibited a significantly higher PPV of 0.936 and an NPV of 0.817. These findings indicate that the Tei index, GCS score, and cTnI possess certain predictive value for secondary CCS in patients with sTBI. Conclusions: The study provides valuable insights into the identification of independent risk factors for CCS secondary to sTBI. The findings highlight the significance of right heart Tei index, GCS score, and cTnI as potential predictive factors for CCS in sTBI patients. Further larger-scale studies are warranted to corroborate these findings and to provide robust evidence for the development of early intervention strategies aimed at reducing the incidence of CCS in this patient population.
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BACKGROUND: The re-emergence of dengue virus 4 (DENV-4) has become a public health concern in South America, Southeast Asia and South Asia. However, it has not been known to have caused a local outbreak in China for the past 20 years. The purpose of this study was to elucidate the epidemiology of one local community outbreak caused by DENV-4 in Guangzhou city, China, in 2010; and to determine the molecular characteristics of the genotype II virus involved. CASE PRESENTATIONS: During September and October of 2010, one imported case, a Guangzhou resident who travelled back from Thailand, resulted in 18 secondary autochthonous cases in Guangzhou City, with an incidence rate of 5.53 per 10,000 residents. In indigenous cases, 14 serum samples tested positive for IgM against DENV and 7 for IgG from a total of 15 submitted serum samples, accompanied by 5 DENV-4 isolates. With identical envelope gene nucleotide sequences, the two isolates (D10168-GZ from the imported index case and Guangzhou 10660 from the first isolate in the autochthonous cases) were grouped into DENV-4 genotype II after comparison to 32 previous DENV-4 isolates from GenBank that originated from different areas. CONCLUSIONS: Based on epidemiological and phylogenetic analyses, the outbreak, which was absent for 20 years after the DENV-4 genotype I outbreak in 1990, was confirmed as DENV-4 genotype II and initially traced to the imported index case, a Guangzhou resident who travelled back from Thailand.
Subject(s)
Dengue Virus/classification , Dengue Virus/genetics , Dengue/epidemiology , Dengue/virology , Disease Outbreaks , RNA, Viral/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , China/epidemiology , Cluster Analysis , Contact Tracing , Dengue Virus/isolation & purification , Female , Genotype , Humans , Male , Middle Aged , Molecular Epidemiology , Phylogeny , Thailand , Travel , Young AdultABSTRACT
Objective. To compare and analyze the relevance and applied value of chronic liver disease questionnaire (CLDQ) and Traditional Chinese Medicine liver disease questionnaire (TCMLDQ) in patients with posthepatitic cirrhosis. Methods. The data of 146 patients' scales of CLDQ and TCMLDQ which based on the characteristics of chinese medical symptoms were collected. We made comparative analysis of the relationship between these two scales by the linear regression model and canonical correlation method and evaluated the advantages and disadvantages of two scales about its items setting and dimension definition. Result. There is a negative correlation in total scores between the two scales and the linear regression equation: CLDQ = 239.38 - 1.232TCMLDQ. The further canonical correlation analysis was used to analyze the two extracted canonical correlative variables with significances (P < 0.05), and the results showed that the overall negative correlation between the two scales mainly came from contributions of both the four dimensions of TCMLDQ (CS, GSYX, GYPX, and OS) and the five dimensions of CLDQ (AS, FA, SS, AC, and EF). Conclusion. These two scales have good consistency in the evaluation of severity and life quality of liver cirrhosis patients, so we suggested that TCMLDQ can be used to evaluate the severity and life quality of patients with posthepatitic cirrhosis.
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To report on the validity and reliability of the Chronic Liver Disease Questionnaire (CLDQ) for assessing subjects with posthepatitic B cirrhosis. The CLDQ was administered to 117 healthy volunteers and 297 patients with posthepatitic B cirrhosis. All posthepatic B cirrhosis patients were assessed for the Child-Pugh stage. The entire questionnaire and each individual item was analyzed for precision and reliability. Exploratory factor analysis, responsiveness, and discrimination validity were also assessed. No significant floor effects were detected, but a moderate ceiling effect (less than 30%) was found for the following subscales: abdominal symptoms (AS), activity (AC), and worry (WO). For most items, the ceiling effect was between 30% to 60%. The internal consistency (Cronbach's a) on total scale level was good (a = 0.905), and ranged from 0.442 to 0.848 for the different subscales. The correlation coefficients of the total scale with subscales were above 0.6 (P less than 0.01) for reliability. The CLDQ and subscale scores for healthy controls were higher than those for the patients (P less than 0.001), and were gradated from the patients with Child-Pugh A cirrhosis to those with Child-Pugh B or C cirrhosis. Increase in severity of liver disease was accompanied by lower scores by the CLDQ and 4 out 6 subscales. Exploratory factor analysis moderately reproduced the original factor structure. The CLDQ has good reliability, satisfactory content, responsiveness and discriminant validity, and moderate precision and construct validity. It is useful for effectively evaluating health-related quality of life and curative effect in patients with posthepatitic B cirrhosis.
Subject(s)
Hepatitis B, Chronic/psychology , Liver Cirrhosis/psychology , Quality of Life , Surveys and Questionnaires , Adolescent , Adult , Aged , Case-Control Studies , Chronic Disease , Female , Health Status , Humans , Male , Middle Aged , Pain/physiopathology , Pain/psychology , Psychometrics , Quality of Life/psychology , Reproducibility of Results , Sensitivity and Specificity , Severity of Illness Index , Statistics as Topic , Young AdultABSTRACT
A 26-year-old man who had inhaled a dried pepper 7 years previously was admitted to our hospital for repeated coughing with yellow sputum and occasional hemoptysis. A thoracic high-resolution computed tomography scan revealed a foreign body at the proximal end of the right lower bronchus. We attempted to remove the foreign body by flexible bronchoscopy, but this was unsuccessful because the foreign body fell deeper into the bronchus. After a multidisciplinary team meeting, the foreign body was successfully extracted by bronchoscope suction and forceps under conscious sedation with spontaneous respiration. We avoided rigid bronchoscopy and traumatic surgery, thus decreasing the patient's risk and cost. We herein share our successful experience with this case.