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BACKGROUND: Updated prevalence estimates along the continuum of Alzheimer's disease (AD) can foster a more nuanced and effective approach to managing AD within the current healthcare landscape. OBJECTIVES: This study aims to estimate the prevalence and severity distribution of dementia/AD (including mild, moderate, and severe stages) and all-cause mild cognitive impairment (MCI) in the United States using data from the Health and Retirement Study (HRS). DESIGN: Retrospective study. SETTING: Data from the bi-annual HRS surveys involving in-depth interviews of a representative sample of Americans aged >50 years. PARTICIPANTS: Dementia/AD and all-cause MCI patients from the 4 most recent HRS surveys (2014, 2016, 2018 and 2020). MEASUREMENTS: AD was identified based on diagnosis (self-report). Cognitive performance (modified Telephone Interview of Cognitive Status [TICS-m]) scores in the dementia/AD range were also captured; all-cause MCI was similarly identified using the TICS-m. Dementia/AD and MCI prevalence, as well as the distribution by dementia/AD stage (mild, moderate, or severe), were estimated. Sampling weights developed by HRS were applied to ensure the sample's representativeness of the target population and unbiased estimates for population parameters. RESULTS: Across the four HRS surveys, the total number of HRS respondents ranged from 15,000 to 21,000 (unweighted); 7,000 to 14,000 had TICS-m scores. The estimated prevalence of AD (all severity categories combined) in the 2014, 2016, 2018, and 2020 HRS surveys was 1.2%, 1.2%, 1.3% and 1.0%, respectively using the diagnosis-based approach; using the cognitive performance-based approach, 23-27% patients had scores in the dementia/AD ranges across the 4 surveys. The estimated prevalence of all-cause MCI was consistently 23% in each survey. In the 2020 survey, the distribution of mild, moderate, and severe disease stages was 34%, 45%, and 21%, respectively, in patients self-reporting an AD diagnosis, and 55%, 40%, and 5%, respectively in all patients meeting TICS-m threshold for dementia/AD. CONCLUSION: The prevalence of AD diagnosis based on self-report was approximately 1% across the 4 most recent HRS surveys and may reflect the proportion of patients who have actively sought healthcare for AD. Among HRS survey respondents with cognitive scores available, over 20% were in the dementia/AD range. The distribution of disease by stage differed for self-reported AD diagnosis vs dementia/AD based on cognitive scores. Discordance in estimates of dementia/AD and stage distributions underscores a need for better understanding of clinical practice patterns in AD diagnosis, use of clinical assessment tools, and severity classification in the United States. Accurate patient identification is needed, especially early in the AD disease continuum, to allow for timely and appropriate initiation of new anti-amyloid treatments.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Estados Unidos/epidemiologia , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/diagnóstico , Feminino , Idoso , Masculino , Prevalência , Estudos Retrospectivos , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/diagnóstico , Pessoa de Meia-Idade , Demência/epidemiologia , Demência/diagnóstico , Idoso de 80 Anos ou mais , Índice de Gravidade de Doença , Bases de Dados FactuaisRESUMO
Ascites is the most prevalent complication of decompensated cirrhosis, and approximately 5%-10% of cirrhotic ascites will develop into refractory ascites (RA). With complicated pathogenesis, obscure treatment strategies and poor prognosis, it is still a challenge for physicians to manage RA properly. Tolvaptan (TLV) is a new type of non-peptide selective arginine vasopressin V2 receptor antagonist targeting at suppressing renal water reabsorption, promoting free water excretion and raising blood sodium levels, which provides a new option for the treatment of RA in liver cirrhosis. In this review, we summarized the mechanisms of TLV's effect and described its efficacy, safety and predictive factors of response in treating RA, intending to provide a supplement for clinical application of tolvaptan in the management of RA.
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With the development of medicine, surgery has also experienced the development and evolution from traditional surgery to minimally invasive surgery, and then to super minimally invasive surgery (SMIS). Meanwhile, reducing surgical trauma and preserving and reconstructing nerve function have gradually become new goals of modern vestibular schwannoma (VS) resection surgery. The surgery of VS can be divided into hearing-preserving surgery (retrosigmoid approach and middle fossa approach) and non-hearing-preserving surgery (traditional translabyrinthine approach), according to whether the patient has practical hearing before operation. Improving the hearing preservation rate of hearing-preserving surgery and reconstructing the hearing of patients with non-hearing-preserving surgery are major challenges and hotspots. The traditional translabyrinthine approach has the highest proportion in the Department of Otolaryngology-Head and Neck Surgery, with the advantages of high facial nerve preservation rate and few intracranial complications. However, due to the resection of the cochlear nerve and labyrinth, the cochlea develops fibrosis, and patients lose the opportunity to reconstruct hearing through cochlear implantation. The new modified translabyrinthine approach can preserve the cochlear nerve and effectively reduce cochlear fibrosis, providing an opportunity for cochlear implantation to reconstruct the hearing. This is another important breakthrough in vestibular schwannoma surgery.
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Procedimentos Cirúrgicos Minimamente Invasivos , Neuroma Acústico , Neuroma Acústico/cirurgia , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Nervo Coclear , AudiçãoRESUMO
Objective: To understand the incidence trend of meningococcal meningitis from 1990 to 2023 and major pathogenic serogroups of Neisseria (N.) meningitidis from 2006 to 2023 in China and the time trend of the incidence of meningococcal meningitis caused by main pathogenic serogroups, and provide reference for the prevention and control of meningococcal meningitis. Methods: The study used the data from "National Epidemic Data Compile" from 1990 to 2003 and the data from China Notifiable Infectious Disease Reporting System from 2004 to 2023 to analyze the incidence trend of meningococcal meningitis in China from 1990 to 2023 by Joinpoint regression method. Based on the data of the national meningococcal meningitis surveillance information reporting and management system from 2006 to 2023, the incidence of meningococcal meningitis caused by different serogroups of N. meningitidis was described and analyzed, and the trend χ2 test was performed to analyze the change of the incidence of meningococcal meningitis caused by N. meningitidis A, B, and C. Results: The overall incidence of meningococcal meningitis in China showed a downward trend from 1990 to 2023 [average annual percent change (AAPC)=-14.80%, P<0.001], with the most obvious decline from 2005 to 2012 [annual percent change (APC)=-31.01%, P<0.001]. The incidence of meningococcal meningitis decreased in both men and women (AAPC=-14.69% and -15.05%, both P<0.001). A total of 1 178 serogroup specific cases of meningococcal meningitis were reported in China from 2006 to 2023, the proportion of serogroup C was highest (32.5%), followed by unclassified (22.3%), B (20.1%), A (18.4%), W (4.5%), Y (2.0%) and X (0.2%). The results of trend χ2 test indicated that the incidence of meningococcal meningitis caused by N. meningitidis A and C showed downward trends (both P<0.001) and the incidence of meningococcal meningitis caused by N. meningitidis B showed an upward trend in general population and young children (0-4 years old group) from 2006 to 2023 (both P<0.05). Conclusion: The incidence of meningococcal meningitis showed a downward trend in China from 1990 to 2023, but it is still necessary to pay more attention to the incidence of meningococcal meningitis caused by N. meningitidis B in age group aged 0-4 years and by multi serogroups at same time in general population.
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Meningite Meningocócica , Neisseria meningitidis , Sorogrupo , China/epidemiologia , Humanos , Incidência , Meningite Meningocócica/epidemiologia , Meningite Meningocócica/microbiologia , Neisseria meningitidis/classificação , Feminino , MasculinoRESUMO
The causes and characteristics of gut microbiota abnormalities and whether microbiota manipulation can prevent atherosclerosis in the postmenopausal stage remain to be determined. Aortic oestrogen receptor expression, histological changes and gut microbiota in women before and after menopause were detected. Serum oestrogen levels, systemic inflammation, intestinal oestrogen receptor expression and histological changes, atherosclerosis, and gut microbiota in low density lipoprotein deletion (LDLR-∕-) female mice before and after ovariectomy were tested. This study examined aortic oestrogen receptor expression, histological changes, and gut microbiota in women before and after menopause, and tested serum oestrogen levels, systemic inflammation, intestinal oestrogen receptor expression, histological changes, atherosclerosis, and gut microbiota in low-density lipoprotein receptor knockout (LDLR-∕-) female mice before and after ovariectomy. We demonstrated that the downregulation of oestrogen and oestrogen receptors after menopause promotes gut microbiota disturbance in both women and female mice. We found that gut microbiota disturbance amplifies the intestinal barrier damage and aggravates systemic inflammation, thereby promoting atherosclerosis in female mice. Faecal microbiota transplantation and antibiotics inhibit the proinflammatory properties of gut microbiota and prevent atherosclerosis by reducing intestinal barrier damage in postmenopausal mice. Together, our study highlights the causes of gut microbiota disturbances and the role of microbiota manipulation in preventing atherosclerosis in postmenopausal stage.
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Objective: To investigate the predictive value of cardiopulmonary exercise test (CPET) indexes for major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD). Methods: This study was a retrospective cohort study. CHD patients were consecutively enrolled who procedure CPET before discharge from the Department of Cardiology, General Hospital of Northern Theater Command from November 2015 to September 2021 were enrolled. Demographic information, past medical history, CPET indexes and other baseline data were collected and the patients were followed up. Patients were divided into a MACE group and a control group according to the presence or absence of MACE. A multivariate Cox proportional hazard regression model was used to analyze the CPET indexes with predictive value for MACE in CHD patients. Results: A total of 3 800 patients were eligible for the criterion, age (57.2±8.8) years, 2 920 (76.84%) males. During a follow-up of 1 237 (695, 1 596) days, 390 (10.26%) patients were in MACE group, and 3 410 (89.74%) patients were in control group. In adjusted multivariable analysis, higher metabolic equivalent of tasks (MET) at anaerobic threshold (AT) is an independent protective factor for MACE in patients with CHD (HR=0.75, 95%CI 0.62-0.90, P=0.002), higher VE/VCO2 is an independent risk factor for MACE in CHD patients (HR=1.05, 95%CI 1.02-1.07, P=0.001). Conclusion: In CPET, high MET at AT is an independent protective factor for MACE in patients with CHD, and high VE/VCO2 is an independent risk factor for MACE in CHD patients.
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Doença das Coronárias , Teste de Esforço , Humanos , Teste de Esforço/métodos , Pessoa de Meia-Idade , Masculino , Feminino , Doença das Coronárias/fisiopatologia , Doença das Coronárias/complicações , Estudos Retrospectivos , Prognóstico , Fatores de Risco , Doenças Cardiovasculares/fisiopatologia , Limiar Anaeróbio , Modelos de Riscos ProporcionaisRESUMO
Objective: To evaluate the role of volume management guided by extravascular lung water index(EVLWI) in improving the clinical outcomes and cardiac function for patients with cardiogenic shock. Methods: This study was a single-center, prospective cohort study. Patients with cardiogenic shock admitted to the Department of Cardiovascular Medicine, Shanghai East Hospital from July 2022 to December 2023 were enrolled. Patients were matched 1â¶1 by propensity score and divided into EVLWI group and control group. In the control group, the volume management strategy was determined by the attending physician based mainly on conventional factors, including clinical features, biochemical assessments, and certain blood pressure measurements. In EVLWI group, the volume management plan was formulated by integrating conventional factors with EVLWI derived from pulse index continuous cardiac output (PiCCO) monitoring. Baseline clinical data, in-hospital treatment, and hemodynamic data were collected. Major adverse cardiovascular events and cardiac function related parameters were compared at 30 d after treatment between the two groups. Baseline EVLWI levels were compared between the non-survivors and the survivors in the EVLWI group. The receiver operating characteristic curve was plotted to assess the accuracy of baseline EVLWI and central venous pressure in predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, and subgroup analysis was performed according to ischemic/non-ischemic etiology and with/without use of inotropic drugs. Kaplan-Meier curve was used for survival analysis, with log-rank tests comparing all-cause mortality, cardiac death, and readmission rate for heart failure at 30 d after treatment. Results: A total of 200 patients with cardiogenic shock were enrolled, aged (71.35±12.82) years, 144(72%) males, EVLWI group and control group 100 patients each. Compared with the control group, EVLWI group had lower all-cause mortality (16%(16/100) vs. 42%(42/100), log-rank P<0.01), cardiac death (14%(14/100) vs. 34%(34/100), log-rank P<0.01), and readmission rate for heart failure (4%(4/100) vs. 12%(12/100), log-rank P=0.03) at 30 d after treatment. Subgroup analysis showed that EVLWI-guided volume management was associated with lower all-cause mortality at 30 d after treatment in patients with cardiogenic shock of ischemic or non-ischemic etiology and with or without inotropic drugs (all P<0.05). In EVLWI group, baseline EVLWI levels were higher in non-survivors than those in survivors [(15.99±6.47) ml/kg vs.(9.75±2.55) ml/kg, P<0.01]. The baseline EVLWI could predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, with an area under the receiver operating characteristic curve of 0.84 (95%CI: 0.75-0.94, P<0.01), while the baseline central venous pressure had no predicting value (AUC=0.54, 95%CI: 0.40-0.69, P=0.60). The optimal cutoff value of EVLWI in pridicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock was >10.3 ml/kg. With the optimization of hemodynamic parameters, left ventricular ejection fraction was improved in EVLWI group, and serum levels of N-terminal pro-brain natriuretic peptide, creatinine, alanine aminotransferase and lactic acid were decreased (all P<0.05). Conclusion: EVLWI-guided volume management exerts a beneficial effect on therapeutic decision-making and improves clinical outcomes and cardiac function in patients with cardiogenic shock.
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Água Extravascular Pulmonar , Choque Cardiogênico , Humanos , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Estudos Prospectivos , Prognóstico , Masculino , Feminino , Hemodinâmica , Pontuação de Propensão , Pessoa de Meia-Idade , Estudos de CoortesRESUMO
Objective: To investigate the changes in cardiopulmonary exercise testing (CPET) characteristics before and after the outbreak of COVID-19 in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Methods: This is a cross-sectional study that included ACS patients who underwent PCI at the General Hospital of the Northern Theater Command from July 2018 to February 2023. Based on the timeline of the COVID-19 pandemic, patients were divided into two groups: the pre-pandemic group and the during-pandemic group, with January 2020 as the dividing line. Clinical data were collected from both groups, and a comparative analysis was performed on their postoperative CPET outcomes, including peak oxygen uptake (peak VO2), peak metabolic equivalents (peak MET), and other indicators. Weber's classification was used to assess cardiac function. In addition, the 7-tiem generalized anxiety disorder scale (GAD-7) and the patient health questionnaire-9 (PHQ-9) were used to assess the patients' psychological anxiety and depression states, respectively. Multivariate logistic regression was used to analyze the influencing factors of CPET after PCI. Results: A total of 4 310 post-PCI ACS patients were included, with an average age of (58.7±9.1) years, and 3 464 (80.37%) were male. There were 1 698 patients in the pre-pandemic group and 2 612 patients in the during-pandemic group. The main indicator of the CPET, peak VO2 (15.04±3.93) ml·min-1·kg-1 in the during-pandemic group, was lower than that in the pre-pandemic group (15.52±3.68) ml·min-1·kg-1, and the difference was statistically significant (P<0.001). Multivariate logistic regression analysis showed that advanced age, female gender, high body mass index, elevated high-sensitivity C-reactive protein, reduced high-density lipoprotein cholesterol, smoking history, history of myocardial infarction, more severe ACS classification, and mild to moderate degree of depression were related to poor cardiopulmonary outcomes (P<0.05). Conclusion: The COVID-19 pandemic had a negative impact on the cardiopulmonary outcomes of ACS patients after PCI. Reduced physical activity, and increased psychological stress should be given consideration and attention regarding their impact on patients' cardiopulmonary function.
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Síndrome Coronariana Aguda , COVID-19 , Teste de Esforço , Intervenção Coronária Percutânea , Humanos , COVID-19/epidemiologia , Pessoa de Meia-Idade , Síndrome Coronariana Aguda/fisiopatologia , Masculino , Feminino , Estudos Transversais , SARS-CoV-2 , Idoso , Ansiedade , Depressão/etiologia , Depressão/epidemiologia , Consumo de Oxigênio , PandemiasRESUMO
BACKGROUND: QL1701 is a proposed biosimilar to the reference trastuzumab (Herceptin®). This trial compared the efficacy and safety of QL1701 with the reference trastuzumab in first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. MATERIALS AND METHODS: This randomized, double-blinded, parallel-controlled, phase III equivalence trial was conducted in 73 centers in China. Eligible patients with histologically or cytologically diagnosed HER2-positive metastatic breast cancer were randomly assigned (1 : 1) to receive either QL1701 or reference trastuzumab in combination with docetaxel (every 3 weeks) for eight cycles as the first-line treatment. Then, in patients with objective responses or stable disease, the QL1701 or reference trastuzumab with or without docetaxel was maintained for totally up to 12 months if tolerated. The primary endpoint was 24-week objective response rate (ORR) assessed by an independent review committee (IRC). The equivalence margin was 0.80-1.25 with a 90% confidence interval (CI) for the ORR ratio (QL1701 to reference trastuzumab). RESULTS: Between 29 April 2020 and 15 March 2022, 474 patients were randomized, and 473 received either QL1701 (n = 236) or reference trastuzumab (n = 237). The risk ratio for 24-week ORR was 1.07 (90% CI 0.94-1.21). The 90% CI fell within the pre-specified equivalence margin of 0.80-1.25. The 24-week ORR assessed by IRC was 59.7% (95% CI 53.2% to 66.1%) versus 56.1% (95% CI 49.5% to 62.5%) in QL1701 and the reference trastuzumab, respectively. As of 12 April 2023, there were no notable differences in progression-free survival (median: 8.3 versus 8.4 months) and overall survival (1-year rate: 95.1% versus 93.3%) between the two groups. Safety, pharmacokinetic (PK), and immunogenicity profiles were similar between the two groups. CONCLUSION: QL1701 demonstrated equivalent efficacy and similar safety to the reference trastuzumab when combined with docetaxel in the first-line treatment of patients with HER2-positive metastatic breast cancer, with similar PK and immunogenicity profiles.
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Protocolos de Quimioterapia Combinada Antineoplásica , Medicamentos Biossimilares , Neoplasias da Mama , Docetaxel , Receptor ErbB-2 , Trastuzumab , Humanos , Trastuzumab/uso terapêutico , Trastuzumab/farmacologia , Docetaxel/uso terapêutico , Docetaxel/farmacologia , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Método Duplo-Cego , Adulto , Medicamentos Biossimilares/uso terapêutico , Medicamentos Biossimilares/farmacologia , Medicamentos Biossimilares/administração & dosagem , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , IdosoRESUMO
Sulfuryl fluoride is a kind of pesticide with strong permeability, convenient use at low temperature, non-corrosive and other characteristics, which can kill food pests and has strong lethality to termites. In acute sulfuryl fluoride poisoning, patients can see recurrent convulsions, epileptic electroencephalogram abnormalities such as matrix spikes or high amplitude spikes. In this paper, a patient with sulfuryl fluoride poisoning with convulsion-based mental system symptoms was reported, and after clinical treatment with dexamethasone and phenobarbital sodium, the patient was cured and discharged.
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Convulsões , Humanos , Convulsões/induzido quimicamente , Masculino , Intoxicação por Gás , Adulto , Ácidos Sulfínicos/intoxicação , Recidiva , Praguicidas/intoxicaçãoRESUMO
The neuropsychiatric effects of probiotics, prebiotics, and synbiotics have been gaining attention since the rise of microbial-gut-brain axis research. Nevertheless, some of the findings are inconsistent, and few studies have analysed the similarities and differences in the neuropsychiatric effects of the three comprehensively. To reveal the respective neuropsychiatric effects of probiotics, prebiotics, and synbiotics and synthesise the similarities and differences among the three effects, 47 meta-analyses with 12 types of neuropsychiatric results were integrated under an umbrella review. Probiotics, prebiotics, and synbiotics intake might all be associated with improvements in some neuropsychiatric outcomes, including neuropsychological test outcomes (probiotic and prebiotic), hepatic encephalopathy outcomes (probiotic, prebiotic, and synbiotic), instant memory in patients with Alzheimer's disease (probiotic), depressive symptoms (probiotic, prebiotic and synbiotic), mood states and psychiatric distress (probiotic), overall mental health (probiotic), neurological function (probiotic), brain-derived neurotrophic factor (BDNF) concentration (probiotic and synbiotic), and Pittsburgh Sleep Quality Index (PSQI) score (probiotic). All three are similar in that the intake of probiotics, prebiotics, and synbiotics might be associated with improvements in hepatic encephalopathy outcomes and depressive symptoms, both probiotic and synbiotic intake might be associated with elevated BDNF concentrations, and both probiotic and prebiotic intake might be associated with improved neuropsychological test results. The difference between the three is that the neuropsychiatric effects of probiotics might be more widespread and be reflected in the fact that probiotic intake might also be associated with improvements in mood states and psychiatric distress, overall mental health, neurological function, Alzheimer's disease patients' instant memory, and PSQI score. Probiotics might be the best and most promising option for improving neuropsychiatric outcomes. In the future, in addition to requiring more high-quality meta-analyses, further preclinical studies are needed to explore specific relevant mechanisms and determine true causal relationships.
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Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients'suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aimsto establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. Temporomandibular joint disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
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Objective: To analyze the variations of serum lymphocyte subsets, immunoglobulins, and complement levels in patients with cheilitis, and to explore the associations between the changes in serum immune levels and the onset of cheilitis. Methods: A retrospective analysis was conducted on 153 patients with cheilitis who visited the Department of Stomatology at the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2023. They were compared with 50 healthy individuals who visited the physical examination department during the same period. The changes of serum lymphocyte subsets, immunoglobulins, and complement levels in patients with cheilitis were analyzed. Main detection indicators as the percentage of total T lymphocytes (T%), helper/inducer T lymphocytes (CD4+T%), absolute numbers of total T lymphocytes (T#), absolute numbers of helper/inducer T lymphocytes (CD4+T#), percentage of NK cells (NK%), absolute numbers of B lymphocytes (B#), immunoglobulins IgG, IgM and complement C3, C4 were included. Multivariate logistic regression was used to explore the relationship between serum lymphocyte subsets, immunoglobulins, complement levels and cheilitis. Subgroup analysis was further conducted on patients with cheilitis based on gender, age, cheilitis type and severity. Results: The levels of T% [69.54% (64.41%, 75.14%)], CD4+T% [(35.09±7.10)%], T# [1 328.00 (1 054.00, 1 560.50)], and CD4+T# [653.00 (505.00, 831.50)] in the cheilitis group were significantly lower than those in the control group respectively [72.33% (69.41%, 75.47%), (39.07±5.84)%, 1 483.50 (1 245.75, 1 805.25), 769.00 (687.25, 933.00), with the corresponding statistical test results of Z=-2.64, P=0.008; t=3.58, P<0.001; Z=-2.80, P=0.005; Z=-3.80, P<0.001]. The level of NK% [16.21% (12.16%, 21.29%)] was significantly higher in the cheilitis group compared to the control group [14.61% (10.97%, 17.87%)] (Z=-2.28, P=0.023). IgG [12.29 (10.77, 13.73) g/L] and IgM levels [1.18 (0.86, 1.58) g/L] were significantly higher in the cheilitis group than in the control group respectively [11.52 (10.16, 12.91) g/L, 0.99 (0.77, 1.26) g/L] (Z=-2.24, P=0.025; Z=-2.10, P=0.036), while complement C3 [(1.09±0.17) g/L] and C4 levels [0.23 (0.19, 0.28) g/L) were significantly lower in the cheilitis group compared to the control [(1.18±0.17) g/L, 0.31(0.24, 0.35) g/L] (t=3.10, P=0.002; Z=-4.79, P<0.001). Logistic regression analysis showed that elevated IgG (P=0.021), decreased C4 (P<0.001), decreased CD4+T% (P=0.003), and decreased T# (P=0.035) were independent influencing factors for the occurrence of cheilitis. The rate of abnormal lymphocyte immune analysis in the cheilitis group [68.0% (104/153)] was significantly higher than that in the control group [24.0% (12/50)] (=29.76, P<0.001). The rate of abnormal immunoglobulin and complement detection in the cheilitis group [41.8% (64/153)] was significantly higher than that in the control group [4.0% (2/50)] (=24.58, P<0.001). The rate of detection abnormalities in female patients with cheilitis [51.5% (53/103)] was significantly higher than in male ones [22.0% (11/50)] (=12.00, P=0.001). Patients with granulomatous cheilitis had significantly lower levels of T# [1 136.50 (663.75, 1 310.50)] and B# [162.50 (104.00, 225.50)] compared to those with chronic cheilitis [1 366.00 (1 063.03, 1 602.00), 202.48 (148.00, 298.00)] (Z=-2.35, P=0.019; Z=-2.16, P=0.031). Conclusions: Patients with cheilitis exhibit a certain degree of imbalance on cellular immunity, humoral immunity, and innate immunity, which may be related to the onset of cheilitis.
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To reduce the working coefficient and jitter of the three-electrode gas switch used in linear transformer drivers, a novel trigger method that uses a nanosecond pulse in cooperation with the microplasma jet generated by capillary discharge was developed. A microplasma jet was generated by the nanosecond trigger pulse and injected into the follow-up breakdown gap of the gas switch to decrease the working coefficient. The influence of capillary parameters on the development of the microplasma jet was simulated. The results showed that the microplasma jet significantly reduced the breakdown delay time, jitter, and working coefficient. Increasing the capillary length and decreasing the diameter results in better triggered breakdown performance. Furthermore, the gas switch triggered by a positive pulse exhibits a lower breakdown delay and jitter. Combined with the intensified charge coupled device's shooting results, it can be concluded that the microplasma jet has a distinct influence on streamer formation, which is important for improving the working performance of the gas switch.
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Epidemiologic studies have implicated the gut microbiota in acute kidney injury (AKI), but the causal relationship is unclear. Using Mendelian randomisation, we explored the causal role of gut microbiota in the development of acute kidney injury after excluding confounding and reverse causality. Mendel randomised (MR) study was conducted using data from intestinal microbiota and genome-wide association studies (GWAS) disease of acute kidney injury and the sequencing data of case-control study confirmed this finding. The summary statistics of intestinal microbiota (n = 13,266) conducted by MiBioGen Alliance was taken as the exposure, while the statistics of acute kidney injury obtained from FinnGen Alliance data (2,383 cases and 212,841 controls) were taken as the results. A total of 42 patients were included in this case-control study. Evidence for the protective causal associations of the genus Flavonifractor id.2059 with AKI was found in inverse variance weighting (odds ratio = 0.48 [95% confidence interval, 0.32-0.72]; P = 0.0003). Additionally, a case-control study showed that the relative abundance of the genus Flavonifractor id.2059 ( P = 0.0169) in septic non-AKI patients was higher than that in septic AKI patients. Compared with S-AKI patients who died within 28 days, the relative abundance of the genus Flavonifractor id.2059 in surviving patients was higher ( P = 0.0281). Phylogenetic analysis showed that OTU68 and HQ455040.1334-739 (genus Flavonifractor, Genetic similarity: 100%), as well as OTU2271 and LT598575.1365-770 (genus Pseudoflavonifractor, Genetic similarity: 100%), have closest genetic ties. Correlation analysis showed that the genus Flavonifractor id.2059 was related to the creatinine value (Spearman correlation: -0.379, P = 0.013). The present study demonstrates that the genus Flavonifractor id.2059 is associated with a reduced risk of AKI, revealing potential implications for the prevention and treatment of acute kidney injury.
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OBJECTIVE: To investigate the role of high-mobility group AT-hook 2 (HMGA2) in osteogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs) and the effect of Hmga2 knockdown for promoting bone defect repair. METHODS: Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs. The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2. Primary mouse ADSCs (mADSCs) were transfected with Hmga2 siRNA, and the changes in osteogenic differentiation of the cells were evaluated using alkaline phosphatase staining and Alizarin red S staining. The expressions of osteogenic markers Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcein (OCN) in the transfected cells were detected using RT-qPCR and Western blotting. In a mouse model of critical-sized calvarial defects, mADSCs with Hmga2-knockdown were transplanted into the defect, and bone repair was evaluated 6 weeks later using micro-CT scanning and histological staining. RESULTS: GEO database analysis showed that HMGA2 expression was upregulated during adipogenic differentiation of ADSCs. Protein-protein interaction network analysis suggested that the potential HMGA2 targets in osteogenic differentiation of ADSCs included SMAD7, CDH1, CDH2, SNAI1, SMAD9, IGF2BP3, and ALDH1A1. In mADSCs, Hmga2 knockdown significantly upregulated the expressions of RUNX2, OPN, and OCN and increased cellular alkaline phosphatase activity and calcium deposition. In a critical-sized calvarial defect model, transplantation of mADSCs with Hmga2 knockdown significantly promoted new bone formation. CONCLUSION: HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs, and Hmga2 knockdown significantly promotes osteogenic differentiation of ADSCs and accelerates ADSCs-mediated bone defect repair in mice.
Assuntos
Diferenciação Celular , Proteína HMGA2 , Células-Tronco Mesenquimais , Osteogênese , Animais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Proteína HMGA2/genética , Proteína HMGA2/metabolismo , Camundongos , Tecido Adiposo/citologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , RNA Interferente Pequeno/genética , Técnicas de Silenciamento de Genes , Adipogenia/genéticaRESUMO
OBJECTIVES: The present study aims to develop an effective risk-prediction score (RPS) to improve screening efficiency and contribute to secondary prevention of colorectal cancer (CRC). STUDY DESIGN: Screening for colorectal lesions. METHODS: 14,398 high-risk individuals aged 50-65 years were included. The baseline characteristics of participants with and without colorectal lesions (CL) were compared using a Chi-squared test. The overall population was randomly split into a training set and a test set in the ratio of 80% and 20%. One-factor and multifactor logistic regression analyses were performed in the training set to construct the RPS (scores of 0-9.62). Area under curve (AUC) was calculated as an estimate of predictive performance using the receiver-operating characteristic (ROC) curve in the test set. RESULTS: In the study population, being male, advanced age, current or previous smoking, weekly alcohol consumption, high body mass index (BMI ≥24 kg/m2), and previously detected colonic polyp were associated with higher risk of CL. Compared to the low-risk group (0-2.31 points), the ORs and 95% confidence intervals (CIs) for the moderate-risk group (2.31-3.85 points) and high-risk group (3.85-8.42 points) were 1.58 (1.44, 1.73) and 2.52 (2.30, 2.76), respectively. For every 1-point increase in score, participants had a 27% increased risk of CL (OR:1.27, 95% CI: 1.24, 1.30). For participants with CL predicted by RPS, the area under the working characteristic curve was 0.61 (P < 0.001). CONCLUSION: Our RPS can quickly and efficiently identify multiple lesions of the colorectum. Combining RPS with existing screening strategies facilitates the identification of very high-risk individuals and may help to prevent CRC.