RESUMO
BACKGROUND: The dynamics of viral shedding and the specific humoral response against monkeypox virus (MPXV) have not been well characterized in patients across their disease course during hospitalisation. The aim of this study was to determine the viral load and the levels of antibodies against MPXV using longitudinal paired-collected samples from hospitalized patients. METHODS: Patients who were hospitalised with mpox were recruited at Beijing Ditan Hospital Capital Medical University in China between June 2 and September 23, 2023. Paired samples, including samples from skin lesions, the oropharynx, saliva, faeces, urine, plasma, and serum, were serially collected at days 1, 3, 7, and 14 after admission until discharge. Not all of the patients had samples obtained at all of the timepoints. All the samples were analysed via quantitative PCR. Virus isolation was performed by using clinical samples and Vero cells. The presence of IgM, IgA, IgG, and neutralising antibodies (NAbs) against MPXV was evaluated. The first collected plasma sample was taken when the patient was hospitalised, and the levels of cytokines and chemokines were measured in the sample. The demographic data, smallpox vaccination status, history of known exposure to MPVX, HIV status and other clinical data were collected using a standard case report form. FINDINGS: A total of 510 specimens were serially collected from 39 recruited people with mpox. Among all the samples, the skin lesions had the highest viral DNA detection rates and viral loads, and the saliva samples had the second highest rates and viral loads. One day before discharge, 85% of the dry scrabs (median Ct 28.2, range 19.0-38.3) and 70% of the saliva samples (median Ct 32.4, range 24.5-38.1) were positive for viral DNA, Of which, 23.1% of dry scrabs were positive in viral culture. The rate of viral DNA detection in the oropharyngeal, saliva, and faecal samples decreased with time, while the rates in the plasma, serum, and urine samples increased quickly before 10 days post symptom onset (PSO). The median days of appearance of MPXV-IgM, MPXV-IgA, MPXV-IgG, and NAb were at 8 (interquartile range [IQR] 7-9), 9 (7-10), 12 (9-15), and 12 (9-15) PSO, respectively. The IgM, IgA, IgG, and NAb titres increased with time. Between days 11 and 21 PSO, the NAb titres were lower in people living with HIV (PWH) than in people living without HIV (PWOH). Increased NAb titres were associated with decreased viral loads in the saliva (r = 0.28, p = 0.025), faeces (r = 0.35, p = 0.021), plasma (r = 0.30, p = 0.0044), and serum samples (r = 0.37, p = 0.001). Compared with PWOH, PWH had higher plasma levels of MIP-1α, MIP-1ß, G-CSF, IL-4, and FGF-basic. INTERPRETATION: The high positive viral culture rate of clinical samples of patients when they are discharged from the hospital indicates that effective public health management strategies are needed for people with mpox. The low NAb titres and high levels of cytokines in PWH shows that earlier treatment is needed to control inflammation in high-risk populations. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences, Fundamental Research Funds for the Central Universities for Peking Union Medical College, National Key R&D Program of China.
Assuntos
Anticorpos Antivirais , Citocinas , Hospitalização , Carga Viral , Humanos , Masculino , Feminino , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Adulto , China/epidemiologia , Estudos Longitudinais , Pessoa de Meia-Idade , Citocinas/sangue , Mpox/virologia , Mpox/imunologia , Mpox/diagnóstico , Mpox/epidemiologia , Estudos Prospectivos , Monkeypox virus/imunologia , Adulto Jovem , Eliminação de Partículas Virais , Adolescente , Idoso , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Animais , Inflamação/virologia , Inflamação/imunologiaRESUMO
Purpose: This research investigated the impact of the COVID-19 pandemic on the mental well-being and sleep quality of students in higher vocational colleges in Sichuan, China, identifying key factors influencing their psychological health during this period. Methods: Between January and February 2022, a comprehensive survey was conducted among students from several higher vocational colleges in Sichuan, utilizing a randomized selection approach to involve 3,300 participants. Data were collected through direct interviews executed by skilled interviewers. Results: Out of 3,049 valid responses, a significant number reported experiencing symptoms of poor mental health, anxiety, depression, and insomnia, with prevalence rates of 21.2%, 9.7%, 14.1%, and 81.9%, respectively. Factors contributing positively to mental health and sleep included a higher family economic status, reduced stress from the pandemic, and decreased online activity. Conversely, lack of physical activity post-pandemic, disruptions to education and employment, and deteriorating relationships emerged as negative influencers. Interestingly, a lack of pre-pandemic mental health knowledge acted as a protective factor against insomnia. Conclusion: The ongoing management of COVID-19 has notably influenced the psychological and sleep health of vocational college students, driven by economic, emotional, lifestyle, and educational factors. The findings underscore the necessity for targeted interventions to address these challenges effectively.
Assuntos
COVID-19 , Saúde Mental , Distúrbios do Início e da Manutenção do Sono , Qualidade do Sono , Estudantes , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , China/epidemiologia , Masculino , Estudantes/psicologia , Feminino , Universidades , Adulto Jovem , Adulto , Inquéritos e Questionários , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Depressão/epidemiologia , Ansiedade/epidemiologia , Adolescente , SARS-CoV-2 , PrevalênciaRESUMO
Objective: This study aims to analyze the association between the occurrence of thyroid nodules and various factors and to establish a risk factor model for thyroid nodules. Methods: The study population was divided into two groups: a group with thyroid nodules and a group without thyroid nodules. Regression with the least absolute shrinkage and selection operator (Lasso) was applied to the complete dataset for variable selection. Binary logistic regression was used to analyze the relationship between various influencing factors and the prevalence of thyroid nodules. Results: Based on the screening results of Lasso regression and the subsequent establishment of the Binary Logistic Regression Model on the training dataset, it was found that advanced age (OR=1.046, 95% CI: 1.033-1.060), females (OR = 1.709, 95% CI: 1.342-2.181), overweight individuals (OR = 1.546, 95% CI: 1.165-2.058), individuals with impaired fasting glucose (OR = 1.590, 95% CI: 1.193-2.122), and those with dyslipidemia (OR = 1.588, 95% CI: 1.197-2.112) were potential risk factors for thyroid nodule disease (p<0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve for the Binary Logistic Regression Model is 0.68 (95% CI: 0.64-0.72). Conclusions: advanced age, females, overweight individuals, those with impaired fasting glucose, and individuals with dyslipidemia are potential risk factors for thyroid nodule disease.
Assuntos
Dislipidemias , Nódulo da Glândula Tireoide , Feminino , Humanos , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/diagnóstico , Modelos Logísticos , Sobrepeso/complicações , Fatores de Risco , GlucoseRESUMO
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder with a high rate of recurrence. This study aimed to explore biomarkers for identifying patients with recurrent CRSwNP (rCRSwNP). METHODS: We recruited two independent cohorts. In the discovery cohort, rCRSwNP patients and non-recurrent CRSwNP (non-rCRSwNP) patients were recruited, and the serum proteomic profile was characterized. The top 5 upregulated and downregulated proteins were confirmed in the validation cohort by ELISA, WB, and qRT-PCR, and their predictive values for postoperative recurrence were assessed. In vitro, human nasal epithelial cells (HNEpCs) were employed to assess the ability of candidate proteins to induce epithelial-mesenchymal transition (EMT). RESULTS: Serum proteomics identified 53 different proteins, including 30 increased and 23 decreased, between the rCRSwNP and non-rCRSwNP groups. ELISA results revealed that serum levels of CD163 and TGF-ß1 were elevated, CD109 and PRDX2 were decreased in the rCRSwNP group compared to the non-rCRSwNP group, and serum CD163, TGF-ß1, and CD109 levels were proved to be associated with the risk of postoperative recurrence. In addition, qRT-PCR and WB revealed that tissue CD163, TGF-ß1, and CD109 expressions in rCRSwNP patients were enhanced compared to those non-rCRSwNP patients. Kaplan-Meier analysis showed that increased CD163 and TGF-ß1 expression and decreased CD109 expression are associated with the risk of recurrence in CRSwNP patients. Receiver operating characteristic curves showed that TGF-ß1 and CD109 had superior diagnostic performances for rCRSwNP. In vitro experiments showed that TGF-ß1 promoted EMT in HNEpCs, and overexpression of CD109 reversed this effect. Functional recovery experiments confirmed that CD109 could attenuate EMT in HNEpCs by inhibiting the TGF-ß1/Smad signaling pathway, attenuating EMT in epithelial cells. CONCLUSION: Our data suggested that TGF-ß1 and CD109 might serve as promising predictors of rCRSwNP. The TGF-ß1/Smad pathway was implicated in fostering EMT in epithelial cells, particularly those exhibiting low expression of CD109. Consequently, the absence of CD109 expression in epithelial cells could be a potential mechanism underlying rCRSwNP.
Assuntos
Antígenos CD , Proteínas Ligadas por GPI , Pólipos Nasais , Proteínas de Neoplasias , Rinossinusite , Humanos , Antígenos CD/sangue , Doença Crônica , Transição Epitelial-Mesenquimal , Proteínas Ligadas por GPI/sangue , Pólipos Nasais/sangue , Pólipos Nasais/cirurgia , Proteínas de Neoplasias/sangue , Proteômica , Rinossinusite/sangue , Rinossinusite/cirurgia , Fatores de Transcrição , Fator de Crescimento Transformador beta1/sangue , Recidiva , Masculino , Feminino , AdultoRESUMO
We introduce a climate intervention strategy focused on decreasing water vapor (WV) concentrations near the tropopause and in the stratosphere to increase outbound longwave radiation. The mechanism is the targeted injection of ice-nucleating particles (INP) in air supersaturated with respect to ice at high altitudes in the tropical entryway to the stratosphere. Ice formation in this region is a critical control of stratospheric WV. Recent airborne in situ data indicate that targeting only a small fraction of air parcels in the region would be sufficient to achieve substantial removal of water. This "intentional stratospheric dehydration" (ISD) strategy would not counteract a large fraction of the forcing from carbon dioxide but may contribute to a portfolio of climate interventions by acting with different time and length scales of impact and risk than other interventions that are already under consideration. We outline the idea, its plausibility, technical hurdles, and side effects to be considered.
RESUMO
Background: Individuals with eosinophilic chronic rhinosinusitis with nasal polyps(eCRSwNP) exhibited worse outcomes and higher postoperative recurrence rates. This study aimed to identify biomarkers that can aid in the early differentiation of eCRSwNP and enhance our comprehension of its pathophysiology. Methods: We recruited two independent cohorts. In the discovery cohort, CRSwNP was categorized into eCRSwNP and non-eosinophilic CRSwNP(neCRSwNP), and serum proteomics was performed to identify differentially expressed proteins between the two groups. These candidate proteins were chosen and confirmed in the validation cohort using an enzyme-linked immunosorbent assay (ELISA), Western blot (WB), quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescence (IF), and their predictive values and associations with tissue eosinophilic pathophysiology were evaluated. Results: We identified a total of 39 differential proteins between the two groups, including 20 proteins upregulated and 19 downregulated in the eCRSwNP group. Further validation was conducted on the top 5 proteins that were up or down-regulated. Results from the ELISA showed that levels of serum MRC1, CDH13, and MMP2 were significantly higher, TRIM28 was lower in the eCRSwNP group compared to the neCRSwNP group (all P<0.05), and serum MRC1 (AUC=0.742, P<0.001) and MMP2 (AUC=0.766, P<0.001) levels exhibited promising predicting values for eCRSwNP. Moreover, qRT-PCR and WB analysis found that MMP2 and MRC1 expressions were enhanced in the eCRSwNP group compared to the neCRSwNP group (all P<0.01), and their levels were positively correlated with the number and percentages of tissue eosinophils (all P<0.01). The IF suggested that MMP2 and MRC1 were overexpressed in the nasal polyps tissues of eCRSwNP patients, and MMP2 was mainly located on eosinophils. Conclusion: Circulating proteins identified by proteomics could serve as potential preoperative biomarkers for distinguishing eCRSwNP. Among them, MMP2 was enhanced in eCRSwNP and correlated with tissue eosinophilia, which provided valuable insights into the pathophysiology of eCRSwNP.
RESUMO
Objectives: To evaluate the efficacy of miniprobe endoscopic ultrasonography for the diagnosis and adjuvant treatment of patients with colorectal submucosal lesions. METHODS: The retrospective study was conducted at the Beijing Chao-Yang Hospital, Capital Medical University, China, and comprised data from January 1, 2016, to July 31, 2021, related to patients of either gender with colorectal submucosal lesions who underwent miniprobe endoscopic ultrasonography. The findings were compared with biopsy specimens and clinical diagnoses. Diagnostic features of miniprobe endoscopic ultrasonography were assessed along with its accuracy. Data was analysed using R 4.1.2. RESULTS: Of the 237 patients, 121(51.1%) were female and 116(48.9%) were male. The overall mean age was 55.6±12.9 years. Miniprobe endoscopic ultrasonography successfully imaged all 237(100%) colorectal submucosal lesions, and 188(79.3%) had consistent results compared to histopathological findings. The majority of lesions were <10mm 102(43.4%) or 10-19mm 84(35.7%) in size. Those detected with high echogenicity were 126(53.2%) and those with low/low-medium echogenicity were 83(35.0%). Tumour size 10-19mm and uneven echo quality significantly increased the accuracy of miniprobe endoscopic ultrasonography (p<0.05). CONCLUSIONS: Miniprobe endoscopic ultrasonography was able to provide precise information about the size, layer of origin, echogenicity and border of colorectal submucosal lesions, and had a high accuracy in the differential diagnosis of such lesions.
Assuntos
Neoplasias Colorretais , Endossonografia , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Endossonografia/métodos , Estudos Retrospectivos , China , Diagnóstico Diferencial , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologiaRESUMO
OBJECTIVES: Metabolic Syndrome (MetS) has been established as a significant factor in the pathogenesis of numerous chronic inflammatory conditions. However, its role in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is unknown. This study aims to investigate the association between MetS, its components, and the risk of postoperative recurrence in Chinese patients with CRSwNP. METHODS: A retrospective cohort study was conducted on CRSwNP patients who underwent endoscopic sinus surgery in our hospital. Patients were divided into MetS and non-MetS groups, and the clinical characteristics and recurrence rates were compared. All CRSwNP patients were followed up for more than 2-years and further categorized into non-recurrent and recurrent groups. Binary logistic regression analyses were performed to examine the effects of MetS and its components on the risk of postoperative recurrence. RESULTS: A total of 555 CRSwNP patients were enrolled in the present study, 157 patients were included in the MetS group and 398 patients were categorized into the non-MetS group. The recurrence rate in the MetS group was significantly higher compared to the non-MetS group (pâ¯<â¯0.05). The rate of MetS, overweight or obesity, hyperglycemia and dyslipidemia were higher in the recurrent group in comparison with the non-recurrent group (pâ¯<â¯0.05). Multivariate logistic regression analysis suggested that MetS, overweight or obesity, hyperglycemia, dyslipidemia, and accompanying allergic rhinitis were associated with the risk of postoperative recurrence of CRSwNP (pâ¯<â¯0.05). Moreover, adjusted and unadjusted regression models showed that MetS was an independent risk factor for postoperative recurrence of CRSwNP, and the risk increased with more components of MetS included (pâ¯<â¯0.05). CONCLUSION: Our findings revealed that MetS independently increased the risk of postoperative recurrence in patients with CRSwNP, with the risk escalating as the number of MetS components increased. Moreover, accompanying allergic rhinitis was also demonstrated to be a potential risk factor for CRSwNP recurrence. LEVEL OF EVIDENCE: Level 4.
Assuntos
Dislipidemias , Hiperglicemia , Síndrome Metabólica , Pólipos Nasais , Rinite Alérgica , Rinite , Rinossinusite , Sinusite , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/cirurgia , Rinite/complicações , Rinite/cirurgia , Síndrome Metabólica/complicações , Estudos Retrospectivos , Sobrepeso/complicações , Sinusite/complicações , Sinusite/cirurgia , Rinite Alérgica/complicações , Obesidade/complicações , Dislipidemias/complicações , Hiperglicemia/complicações , Doença Crônica , RecidivaRESUMO
IMPORTANCE: Phage therapy is gaining traction as an alternative to antibiotics due to the rise of multi-drug-resistant (MDR) bacteria. This study assessed the pharmacokinetics and safety of PA_LZ7, a phage targeting MDR Pseudomonas aeruginosa, in mice. After intravenous administration, the phage showed an exponential decay in plasma and its concentration dropped significantly within 24 h for all dosage groups. Although there was a temporary increase in certain plasma cytokines and spleen weight at higher dosages, no significant toxicity was observed. Therefore, PA_LZ7 shows potential as an effective and safe candidate for future phage therapy against MDR P. aeruginosa infections.
Assuntos
Bacteriófagos , Infecções por Pseudomonas , Fagos de Pseudomonas , Animais , Camundongos , Fagos de Pseudomonas/genética , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Infecções por Pseudomonas/terapia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosaRESUMO
BACKGROUND: It is unclear about the mutual impact of COVID-19 related psychological stress and infection on mental health of adolescent and youth students. This study aimed to explore the mutual impact of COVID-19 related psychological stress and infection on mental health problems among students. METHODS: This study was conducted from December 14, 2022 to February 28, 2023 in Sichuan, China. Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, PTSD Checklist for DSM-5, Insomnia Severity Index, and Internet Addiction Test were used. Participants were grouped by COVID-19 infection and psychological stress level. The differences among groups were compared, and logistic regression analysis was used to investigate risk factors for depression, anxiety, PTSD and insomnia among groups. RESULTS: Of 90,118 participants, 82,873 (92.0 %) finished the questionnaires and were included in the study. Of 82,873 participants, 33,314 (40.2 %) reported to be infected with COVID-19. Participants had depression symptoms (38.1 %), anxiety symptoms (31.8 %), PTSD (33.9 %), insomnia (34.0 %), and internet addiction (60.3 %). Compared with participants uninfected with low psychological stress level, the risk for symptoms of depression, anxiety, PTSD and insomnia increased by 9.6 %, 12.3 %, 6.6 %, and 12.0 % in participants infected with low psychological stress level (p < 0.001), 106.8 %, 125.9 %, 125.2 %, and 95.7 % in participants uninfected with high psychological stress level (p < 0.001), and 147.3 %, 161.1 %, 158.7 %, and 141.0 % in participants infected with high psychological stress level (p < 0.001). LIMITATION: This study is a cross-sectional design, and no causal associations should be inferred. Infection status was based on self-report of participants with infectious symptoms. CONCLUSION: COVID-19 related psychological stress and infection per se have mutually overlapping impacts on mental health problems among students. Further health policies and psychosocial interventions should be developed to reduce mutually overlapping impact and improve the long-term mental health among students.
Assuntos
COVID-19 , Distúrbios do Início e da Manutenção do Sono , Adolescente , Humanos , COVID-19/epidemiologia , Saúde Mental , SARS-CoV-2 , Pandemias , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Estudos Transversais , Ansiedade/diagnóstico , China/epidemiologia , Depressão/diagnósticoRESUMO
Abstract Objectives Metabolic Syndrome (MetS) has been established as a significant factor in the pathogenesis of numerous chronic inflammatory conditions. However, its role in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is unknown. This study aims to investigate the association between MetS, its components, and the risk of postoperative recurrence in Chinese patients with CRSwNP. Methods A retrospective cohort study was conducted on CRSwNP patients who underwent endoscopic sinus surgery in our hospital. Patients were divided into MetS and non-MetS groups, and the clinical characteristics and recurrence rates were compared. All CRSwNP patients were followed up for more than 2-years and further categorized into non-recurrent and recurrent groups. Binary logistic regression analyses were performed to examine the effects of MetS and its components on the risk of postoperative recurrence. Results A total of 555 CRSwNP patients were enrolled in the present study, 157 patients were included in the MetS group and 398 patients were categorized into the non-MetS group. The recurrence rate in the MetS group was significantly higher compared to the non-MetS group (p< 0.05). The rate of MetS, overweight or obesity, hyperglycemia and dyslipidemia were higher in the recurrent group in comparison with the non-recurrent group (p< 0.05). Multivariate logistic regression analysis suggested that MetS, overweight or obesity, hyperglycemia, dyslipidemia, and accompanying allergic rhinitis were associated with the risk of postoperative recurrence of CRSwNP (p< 0.05). Moreover, adjusted and unadjusted regression models showed that MetS was an independent risk factor for postoperative recurrence of CRSwNP, and the risk increased with more components of MetS included (p< 0.05). Conclusion Our findings revealed that MetS independently increased the risk of postoperative recurrence in patients with CRSwNP, with the risk escalating as the number of MetS components increased. Moreover, accompanying allergic rhinitis was also demonstrated to be a potential risk factor for CRSwNP recurrence. Level of evidence: Level 4.
RESUMO
Objective: The aim of this study was to explore the psychological counseling intention of college students, the attitude of seeking psychological help, and the related factors of shame so as to promote the psychological health of college students. Methods: In 4 comprehensive colleges with sound psychological counseling centers, students of different grades were selected and divided into an active help-seeking group (n = 216) and a help-refusal group (n = 270). Students' shame behaviors were evaluated using the Self-Stigma of Seeking Help (SSOSH) scale and Self-Stigma Scale (SSS). The intention of psychological counseling was measured by the General Help-Seeking Questionnaire. The Inventory of Attitudes Toward Seeking Mental Health Services was used to evaluate the psychological status. Data from the above scales were compared through the t-test. Additionally, multiple linear regression analysis was performed to explore the impact of shame on the intention of psychological counseling. Results: The study found that the active help-seeking group scored lower on SSOSH scale compared to those in the help-refusal group (total score: 41.2 ± 9.1 vs. 37.9 ± 8.7, P = .0017). Meanwhile, the help-refusal group had higher scores on the shame dimension of the SSS (16.2 ± 3.9 vs. 5.3 ± 1.1, P = .00085). After adjusting for age, gender, and other variables, multiple linear regression analysis indicated a negative correlation between shame and intention of psychological help and counseling, revealing a significant impact of shame on professional psychological counseling (P < .05). Conclusion: Our study findings suggest that shame has a negative impact on the intention of seeking psychological help and counseling among college students, highlighting the importance of addressing shame-related factors to promote psychological health and encourage the utilization of professional psychological counseling services.
RESUMO
BACKGROUND: The immune system plays a crucial role in initiating, progressing, and disseminating HNSCC. This study aims to investigate the differences in immune microenvironments between 2D-4-culture and 3D-4-culture models of head and neck squamous cell carcinoma (HNSCC) cells (FaDu), human fibroblasts (HF), human monocytes (THP-1), and human endothelial cells (HUVEC). METHODS: For the 3D-4-culture model, FaDu:HF:THP-1 (2:1:1) were inoculated in an ultra-low attachment culture plate, while HUVECs were placed in a transwell chamber. The ordinary culture plate was used for the 2D-4-culture model. Tumor-associated macrophage markers (CD163), tumor-associated fibroblast markers (FAP), and epithelial-mesenchymal transition (EMT) were detected by western blot. Inflammatory cytokines (IL-4, IL-2, CXCL 10, IL-1 ß, TNF-α, CCL 2, IL-17 A, IL-6, IL-10, IFN-γ, IL-12 p 70, CXCL 8, TGFß1) in the supernatant were measured by flow cytometry. HUVEC migration was observed under a microscope. The 3D spheres were stained and observed with a confocal microscope. CCK8 assay was used to detect the resistance of mixed cells to cisplatin in both 2D-4-culture and 3D-4-culture. RESULTS: After three days of co-culture, the 3D-4-culture model showed increased expression levels of CD163 and FAP proteins (both P < 0.001), increased expression of E-cadherin protein and N-cadherin protein expression (P < 0.001), decreased expression of vimentin (P < 0.01) and Twist protein (P < 0.001). HUVEC migration significantly increased (P < 0.001), as did the concentrations of IP-10, MCP-1, IL-6, and IL-8 (all P < 0.001). Confocal microscopy showed that 3D-4-culture formed loose cell clusters on day 1, which gradually became a dense sphere surrounded by FaDu cells invading the inside. After co-culturing for 24 h, 48 h, and 72 h, the resistance of mix cells to cisplatin in 3D-4-culture was significantly higher than in 2D-4-culture (P < 0.01 for all). CONCLUSION: Compared to 2D-4-culture, 3D-4-culture better simulates the in vivo immune microenvironment of HNSCC by promoting fibroblast transformation into tumor-associated fibroblasts, monocyte transformation into tumor-associated macrophages, enhancing endothelial cell migration ability, partial EMT formation in HNSCC cells, and is more suitable for studying the immunosuppressive microenvironment of HNSCC.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Cisplatino , Células Endoteliais/metabolismo , Interleucina-6 , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Fatores de Transcrição , Microambiente TumoralRESUMO
The Hunga Tonga-Hunga Ha'apai (HT-HH) volcanic eruptions on January 13 and 15, 2022, produced a plume with the highest signal in stratospheric aerosol optical depth observed since the eruption of Mt. Pinatubo in 1991. Suites of balloon-borne instruments on a series of launches from Réunion Island intercepted the HT-HH plume between 7 and 10 d of the eruptions, yielding observations of the aerosol number and size distribution and sulfur dioxide (SO2) and water vapor (H2O) concentrations. The measurements reveal an unexpected abundance of large particles in the plume, constrain the total sulfur injected to approximately 0.2 Tg, provide information on the altitude of the injection, and indicate that the formation of sulfuric acid aerosol was complete within 3 wk. Large H2O enhancements contributed as much as ~30% to ambient aerosol surface area and likely accelerated SO2 oxidation and aerosol formation rates in the plume to approximately three times faster than under normal stratospheric conditions.
RESUMO
The eruption of the Hunga Tonga-Hunga Ha'apai volcano on 15 January 2022 offered a good opportunity to explore the early impacts of tropical volcanic eruptions on stratospheric composition. Balloon-borne observations near Réunion Island revealed the unprecedented amount of water vapor injected by the volcano. The enhanced stratospheric humidity, radiative cooling, and expanded aerosol surface area in the volcanic plume created the ideal conditions for swift ozone depletion of 5% in the tropical stratosphere in just 1 week. The decrease in hydrogen chloride by 0.4 parts per million by volume (ppbv) and the increase in chlorine monoxide by 0.4 ppbv provided compelling evidence for chlorine activation within the volcanic plume. This study enhances our understanding of the effect of this unusual volcanic eruption on stratospheric chemistry and provides insights into possible chemistry changes that may occur in a changing climate.
RESUMO
OBJECTIVE: To investigate the clinical efficacy of percutaneous screw fixation combined with minimally invasive transpedicular bone grafting and non-bone grafting in the treatment of thoracolumbar fractures. METHODS: From Janury 2021 to June 2022, 40 patients with thoracolumbar fracture were divided into the experimental group and the control group. There were 26 patients in the experimental group, including 21 males and 5 females with an aberage age of (47.3±12.3) years old, who underwent percutaneous pedicle screw fixation combined with transpedicular autogenous bone grafting. In the control group, 14 patients received percutaneous pedicle screw fixation only. including 7 makes and 7 females with an average age of (50.2±11.2) years old. The operative time, intraoperative blood loss, anterior height ratio of injured vertebrae, Cobb angle, visual analogue score (VAS), MacNab scores, loosening or broken of the implants. were compared and analyzed. RESULTS: There was no significant difference in operation time, intraoperative blood loss, VAS and anterior height ratio of injured vertebrae between the two groups. Compared with the preoperative results, VAS and anterior height ratio of injured vertebrae were improved statistically(P<0.05). For Cobb angle of injured vertebra, there was no significant difference between the two groups before surgery (P=0.766). While at 1 week, 3 months and 12 months after surgery, there were statistically differences between the two groups (P values were 0.042, 0.007 and 0.039, respectively). The Cobb angle of injured vertebrae one year after operation was statistically decreased in both groups compared with that before surgery (P<0.001). One year after surgery, the excellent and good rate of Macnab scores was 96.15% in the experimental group and 92.86% in the control group, and there was no statistical differences between the two groups (P=0.648). There was one patient in the control group suffering superficial wound infection on the third day, which was cured by dressing change and anti-infection treatment. There were no postoperative screw loosening and broken in both groups. CONCLUSION: The two surgical methods have the advantages of less trauma, less pain and quicker recovery, which can restore the height of the injured vertebra, reconstruct the spinal sequence and reduce the fracture of the vertebral body. Transpedicular autogenous bone grafting can increase the stability of the fractured vertebra and maintain the height of the vertebra better after surgery, thus reducing the possibility of complications such as kyphosis, screw loosening and broken.
Assuntos
Parafusos Pediculares , Fraturas da Coluna Vertebral , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Transplante Ósseo , Perda Sanguínea Cirúrgica , Vértebras Lombares/cirurgia , Vértebras Lombares/lesões , Vértebras Torácicas/cirurgia , Vértebras Torácicas/lesões , Fixação Interna de Fraturas/métodos , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Hydrogen sulfide (H2S) promotes microangiogenesis and revascularization after ischemia. Neovascularization starts with the destruction of intercellular junctions and is accompanied by various endothelial cell angiogenic behaviors. Follistatin-like 1 (FSTL1) is a cardiovascular-protective myokine that works against ischemic injury. The present study examined whether FSTL1 was involved in H2S-induced angiogenesis and explored the underlying molecular mechanism. We observed that H2S accelerated blood perfusion after ischemia in the mouse hindlimb ischemia model. Western blot analysis showed that H2S stabilized FSTL1 transcript and increased FSTL1 and Human antigen R (HuR) levels in skeletal muscle. RNA-interference HuR significantly inhibited the H2S-promoted increase in FSTL1 levels. Exogenous FSTL1 promoted the wound-healing migration of human umbilical vein endothelial cells (HUVECs) and increased monolayer endothelial barrier permeability. Immunostaining showed that FSTL1 increased interendothelial gap formation and decreased VE-Cadherin, Occludin, Connexin-43, and Claudin-5 expression. In addition, FSTL1 significantly increased the phosphorylation of Src and VEGFR2. However, the Src inhibitor, not the VEGFR2 inhibitor, could block FSTL1-induced effects in angiogenesis. In conclusion, we demonstrated that H2S could upregulate the expression of FSTL1 by increasing the HuR levels in skeletal muscle, and paracrine FSTL1 could initiate angiogenesis by opening intercellular junctions via the Src signaling pathway.NEW & NOTEWORTHY The myocyte-derived paracrine protein FSTL1 acts on vascular endothelial cells and initiates the process of angiogenesis by opening the intercellular junction via activating Src kinase. H2S can significantly upregulate FSTL1 protein levels in skeletal muscles by increasing HuR expression.
RESUMO
BACKGROUND: 3-acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-boswellic acid (KBA) are the main active components of frankincense as pentacyclic triterpenoids, which are designated by the European Pharmacopoeia 8.0 as the quality standard for the evaluation of Indian frankincense, 2-methoxy-8,12-epoxygermacra- 1(10),7,11-trien-6-one (MCS134) is a non-volatile sesquiterpene compound in myrrh. OBJECTIVE: In this paper, the absorption pharmacokinetics and metabolites of AKBA, KBA and MCS134 after frankincense, myrrh and their compatibility were analyzed, elaborated their absorption and metabolism mechanism and provided the ideas for the research on the bioactive components of frankincense and myrrh compatibility in vivo. METHODS: The area under the blood concentration time curve (AUC), half-life (t1/2) and drug clearance (CL) of AKBA, KBA and MCS134 in rats were analyzed by LC-TQ / MS. The metabolites of AKBA, KBA and MCS134 in rats were analyzed by ultra-high pressure liquid chromatography with a linear ion trap-high resolution Orbitrap mass spectrometry system (UHPLC-LTQ-Orbitrap-MS). RESULTS: The results showed that AKBA, KBA and MCS134 reached the maximum plasma concentration at about 2 h, 2 h and 15 min, respectively. AUC0-t and t1/2 of the three components increased in varying degrees after compatibility, and the clearance/ bioavailability (CL/F) decreased. AKBA, KBA and MCS134 were metabolized in phase I and phase II in rats, and there represented differences before and after compatibility. CONCLUSION: After the compatibility of frankincense and myrrh, the absorption of effective components was improved to some extent, and there were some differences in the metabolites in rats. The results provide ideas for elucidating the in vivo effect mechanism of frankincense and myrrh.
RESUMO
Background: Although the COVID-19 pandemic has greatly changed the way students studied, it is still unknown about the impact of the COVID-19 pandemic on students' academic performance and mental health. Objective: To explore the academic performance and mental health status of middle and high school students after the lifting of COVID-19 restrictions in China. Methods: An online survey was conducted in Sichuan province, China from Dec 14, 2022 to Feb 28, 2023. All participants were students in middle and high schools, recruited via their teachers. The general information, COVID-19-related information, and academic performance were collected. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Internet Addiction Test (IAT) were used to assess the mental health problems. Results: Of 60,268 participants, 36,247 (60.2%) middle and high school students reported that their studies were affected by the COVID-19 pandemic, and 24,864 (41.2%) reported that their academic performance had worsened. The prevalence of depression and anxiety symptoms was 38.4 and 32.7%, respectively. There was a significant association between academic performance change and mental health problems. The logistic regression analysis showed that improved academic performance was a protective factor for depression, and declined academic performance was a risk factor for depression and anxiety. Being COVID-19 infected, family members being infected, with quarantine experience, and with COVID-19-related stigma were risk factors for depression and anxiety. Conclusion: Academic studies and mental health status of middle and high school students in Sichuan, China have been negatively impacted by the COVID-19 pandemic, even after the lifting of COVID-19 restrictions. Students' academic performance, academic concerns, and mental health status should be considered for educational policymakers and institutions to improve students' academic studies and mental well-being.