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1.
Nature ; 609(7928): 685-688, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36131036

RESUMO

Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref. 9). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (AU; Earth-Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.

2.
J Neurosci ; 44(4)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38050135

RESUMO

N-methyl-D-aspartate receptors (NMDARs) are crucial for neuronal development and synaptic plasticity. Dysfunction of NMDARs is associated with multiple neurodevelopmental disorders, including epilepsy, autism spectrum disorder, and intellectual disability. Understanding the impact of genetic variants of NMDAR subunits can shed light on the mechanisms of disease. Here, we characterized the functional implications of a de novo mutation of the GluN2A subunit (P1199Rfs*32) resulting in the truncation of the C-terminal domain. The variant was identified in a male patient with epileptic encephalopathy, multiple seizure types, severe aphasia, and neurobehavioral changes. Given the known role of the CTD in NMDAR trafficking, we examined changes in receptor localization and abundance at the postsynaptic membrane using a combination of molecular assays in heterologous cells and rat primary neuronal cultures. We observed that the GluN2A P1199Rfs*32-containing receptors traffic efficiently to the postsynaptic membrane but have increased extra-synaptic expression relative to WT GluN2A-containing NMDARs. Using in silico predictions, we hypothesized that the mutant would lose all PDZ interactions, except for the recycling protein Scribble1. Indeed, we observed impaired binding to the scaffolding protein postsynaptic protein-95 (PSD-95); however, we found the mutant interacts with Scribble1, which facilitates the recycling of both the mutant and the WT GluN2A. Finally, we found that neurons expressing GluN2A P1199Rfs*32 have fewer synapses and decreased spine density, indicating compromised synaptic transmission in these neurons. Overall, our data show that GluN2A P1199Rfs*32 is a loss-of-function variant with altered membrane localization in neurons and provide mechanistic insight into disease etiology.


Assuntos
Transtorno do Espectro Autista , Epilepsia , Animais , Humanos , Masculino , Ratos , Transtorno do Espectro Autista/metabolismo , Epilepsia/genética , Epilepsia/metabolismo , Neurônios/fisiologia , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais , Sinapses/fisiologia
3.
Clin Radiol ; 79(7): e900-e907, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38599949

RESUMO

AIM: This study aimed to investigate whether computed tomography (CT)-measured erector spinae parameters (ESPs) have diagnostic, severity assessment, and prognostic predictive value in uremic sarcopenia (US). MATERIALS AND METHODS: A total of 202 uremic patients were enrolled and divided into two groups: a control group and a sarcopenia group. Sarcopenia was classified into two types: severe and nonsevere. The area, volume, and density of the erector spinae (ES) were measured using chest CT images, and the relevant ESP, including the erector spinae index (ESI), total erector spinae volume (TESV), erector spinae density (ESD), and erector spinae gauge (ESG) were calculated. The occurrence of adverse events was followed-up for 36 months. The diagnostic value and severity of US were determined using the receiver operating characteristic (ROC) curve. Survival curves diagnosed using CT were plotted and compared with the curve drawn using the gold standard. Cox regression analysis was used to identify independent risk factors associated with survival in US. RESULTS: With an area under the curve (AUC) of 0.840 and 0.739, the combined ESP has diagnostic value and the ability to assess the severity of US. There was no significant difference in the survival curve between the combined ESP for the diagnosis of US and the gold standard (P > 0.05). ESI is a standalone predictor of survival in patients with US. CONCLUSION: ESP measured by CT has diagnostic values for US and its severity, as well as being a predictive value for the prognosis of US.


Assuntos
Sarcopenia , Tomografia Computadorizada por Raios X , Uremia , Humanos , Sarcopenia/diagnóstico por imagem , Sarcopenia/complicações , Masculino , Feminino , Prognóstico , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Uremia/complicações , Uremia/diagnóstico por imagem , Músculos Paraespinais/diagnóstico por imagem , Idoso , Estudos Retrospectivos , Índice de Gravidade de Doença
4.
Public Health ; 229: 50-56, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401192

RESUMO

OBJECTIVES: Mental health has become a significant public health problem that impacts both economic and social development, with severe mental disorders (SMDs) being the top priority. Over recent years, Beijing, China, has introduced several policies to reduce the economic burden on patients with mental health disorders. The aim of this study was to investigate the current status and composition of patients' medical expenses following the introduction of multiple medical policies, explore the factors that may impact the utilisation of medical services and provide a reference and basis for subsequent policy improvements. STUDY DESIGN: Multistage sampling was used to select a representative study population. A retrospective survey was used to collect patient information and data on medical expenses in 2019. METHODS: Descriptive statistics were applied to analyse the current status of patients' medical expenses, and a two-part model was used to examine the factors influencing healthcare utilisation and to model predicted expenses. RESULTS: Among 4940 participants, the average outpatient expenses of patients with SMD who incurred medical expenses were 8373.61 Yuan, and the average hospitalisation expenses were 81,594.05 Yuan. The out-of-pocket expenses were 29.22% of outpatient expenses and 8.13% of inpatient expenses. Factors such as age, household status, economic status, marital status, participation in the Community Free-Medication Service (CFMS) and the type of disease diagnosed influenced the differences in medical expenses and utilisation of services. CONCLUSIONS: The medical expenses of patients with SMD in Beijing are high, but a number of introduced policies have effectively reduced these costs for patients. Future studies should focus on the impact of factors such as age, economic status, participation in the CFMS and the type of disease diagnosed on medical expenses.


Assuntos
Transtornos Mentais , Humanos , Pequim , Estudos Retrospectivos , Atenção à Saúde , Gastos em Saúde , China/epidemiologia
5.
J Environ Manage ; 351: 119726, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38052142

RESUMO

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.


Assuntos
Incêndios , Incêndios Florestais , Ecossistema , Retroalimentação , Florestas , Árvores
6.
Zhonghua Yi Xue Za Zhi ; 104(14): 1155-1159, 2024 Apr 09.
Artigo em Chinês | MEDLINE | ID: mdl-38583046

RESUMO

Objective: To explore the efficacy and effective node of short-term personalized vestibular rehabilitation (ST-PVR) in treating acute unilateral vestibulopathy (AUVP). Methods: A randomized controlled trial was carried out. The AUVP patients who were admitted to the First Affiliated Hospital of Zhengzhou University from July 2022 to March 2023 were selected and randomized to the vestibular rehabilitation (VR) group and control group via computer-generated randomization. Standard care was the medical treatment with betahistine and prednisolone. Meanwhile, the VR group received ST-PVR. All the patients completed the baseline assessment and underwent follow-up assessments at 1 month and 3 months after the treatment. The assessments were consisted of spontaneous nystagmus (NYS), Romberg test (ROM), head thrust test (HTT), visual analogue scale (VAS) for vertigo, dizziness handicap inventory scale (DHI), activities-specific balance confidence scale (ABC), caloric test using video-electronystagmograph (VNG), and video-head impulse test (vHIT). The measurement data that did not conform to normal distribution were represented by M (Q1, Q3). Generalized estimating equation (GEE) was used to analyze the influence of the ST-PVR on the values of these clinical indicators and the VR grading score. The values of clinical indicators and the VR grading score were compared between the two groups at each follow-up point. Results: Seventy-one AUVP patients were included, with 35 cases in the VR group [14 males and 21 females, aged 51 (33, 55) years] and 36 cases in control group [17 males and 19 females, aged 46 (34, 59) years]. There were statistically significant differences in the impact of ST-PVR on the values of clinical indicators between the two groups (ABC: ß=10.89, P<0.001; VAS: ß=-1.64, P<0.001; DHI: ß=-8.70, P<0.001; NYS: ß=26.73, P<0.001; vHIT: ß=1.41, P=0.047; the VR grading score: ß=1.03, P=0.045). The assessments of the VR group in the positive rate of NYS [14.3% (5/35) vs 50.0% (18/36), P<0.001], ROM [48.6% (17/35) vs 55.6% (20/36), P<0.001], directional preponderance (DP) [34.3% (12/35) vs 75.0% (27/36), P<0.001] and DHI [26 (22, 32) vs 36 (30, 60), P=0.001] were significantly lower than that of the control group at 1 month after the treatment. The results showed a statistically significant difference in ABC [88 (80, 90) vs 76 (61, 88), P<0.001], VAS [2 (1, 3) vs 3 (2, 5), P<0.001] at 3-months after the treatment. The VR grading score of the VR group was improved significantly than those of the control group at 1 month after treatment [21 (17, 21) vs 16 (13, 20), P=0.001]. Conclusion: ST-PVR could improve the results of clinical indicators and VR grading score of the AUVP patients effectively after 1 month of the systematical treatment, and alleviate the symptoms and signs of dizziness in the acute phase as early as possible.


Assuntos
Tontura , Vertigem , Feminino , Humanos , Masculino , Terapia por Exercício/métodos , Hospitais , Adulto , Pessoa de Meia-Idade
7.
Zhonghua Wai Ke Za Zhi ; 62(4): 290-301, 2024 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-38432670

RESUMO

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of (M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) µmol/L(range: 5.4 to 722.8 µmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 µmol/L to 85.5 µmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ (P=0.009), hemi-hepatectomy and extended resection (P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1:OR=1.43 (0.61-3.35),P=0.413;T3 vs. T1:OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Masculino , Feminino , Humanos , Tumor de Klatskin/cirurgia , Tumor de Klatskin/patologia , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/patologia , Estudos de Coortes , Resultado do Tratamento , Estudos Retrospectivos , Bismuto , Prognóstico , Hepatectomia , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Bilirrubina
8.
Phys Rev Lett ; 130(21): 216702, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37295086

RESUMO

Ferromagnets are known to support spin-polarized currents that control various spin-dependent transport phenomena useful for spintronics. On the contrary, fully compensated antiferromagnets are expected to support only globally spin-neutral currents. Here, we demonstrate that these globally spin-neutral currents can represent the Néel spin currents, i.e., staggered spin currents flowing through different magnetic sublattices. The Néel spin currents emerge in antiferromagnets with strong intrasublattice coupling (hopping) and drive the spin-dependent transport phenomena such as tunneling magnetoresistance (TMR) and spin-transfer torque (STT) in antiferromagnetic tunnel junctions (AFMTJs). Using RuO_{2} and Fe_{4}GeTe_{2} as representative antiferromagnets, we predict that the Néel spin currents with a strong staggered spin polarization produce a sizable fieldlike STT capable of the deterministic switching of the Néel vector in the associated AFMTJs. Our work uncovers the previously unexplored potential of fully compensated antiferromagnets and paves a new route to realize the efficient writing and reading of information for antiferromagnetic spintronics.

10.
Public Health ; 221: 106-115, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37441994

RESUMO

OBJECTIVES: This systematic review was conducted to estimate the respective prevalence of gonorrhea among two high-risk populations in China and determine the epidemiological features of gonorrhea in them. STUDY DESIGN: Systematic review. METHODS: PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched to identify studies published between January 1, 1990, and October 31, 2022, with gonorrhea prevalence tested by polymerase chain reaction among female sex workers (FSWs) and men who have sex with men (MSM). Meta-regression and subgroup analyses were used to investigate potential factors of heterogeneity across studies. Trend analysis of prevalence was conducted by the Jonckheere-Terpstra method. RESULTS: We identified 88 prevalence data points from 49 studies in China, with 30,853 participants of FSWs and 5523 participants of MSM. Pooled prevalence of gonorrhea among FSWs and MSM were 6.9% (95% confidence interval: 4.6-9.7%) and 2.5% (95% confidence interval: 1.5-3.7%), respectively. The subgroup analyses showed there were period, regional, and specimen collection methods diversities among FSWs, and diversities of the regions and specimen collection anatomical sites were found among MSM, in which the prevalence of rectum and pharynx was significantly higher than the urethra. A decreasing trend in the prevalence of gonorrhea was seen among FSWs (z = -4.03) from 1999 to 2021, not found for MSM in China. CONCLUSION: The prevalence of gonorrhea is high in two high-risk groups in China, with extragenital infections requiring particular attention. The findings of this study will provide evidence to formulate national policy and guidance for gonorrhea prevention and control.


Assuntos
Infecções por Chlamydia , Gonorreia , Infecções por HIV , Profissionais do Sexo , Minorias Sexuais e de Gênero , Masculino , Humanos , Feminino , Gonorreia/epidemiologia , Homossexualidade Masculina , Infecções por Chlamydia/epidemiologia , Prevalência , China/epidemiologia , Infecções por HIV/epidemiologia
11.
Zhonghua Zhong Liu Za Zhi ; 45(2): 160-164, 2023 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-36781237

RESUMO

Objective: To explore the influence factors of poor prognosis of esophageal squamous cell carcinoma (ESCC) and the predictive value of inflammatory reaction indexes including neutrophils and lymphocytes ratio (NLR), platelet and lymphocyte ratio (PLR), monocyte and lymphocyte ratio (MLR) provision and differentiation degree, infiltration depth, lymph node metastasis number on the postoperative recurrence of ESCC. Methods: A total of 130 patients with ESCC who underwent radical resection from February 2017 to February 2019 in Nanyang Central Hospital were selected and divided into good prognosis group (66 cases) and poor prognosis group (64 cases) according to the prognostic effect. The clinical data and follow-up data were collected. Multivariate logistic regression analysis was used to determine the independent influencing factors of poor prognosis. Spearman correlation analysis was used to determine the correlation between preoperative NLR, PLR and MLR with the degree of differentiation, depth of invasion and number of lymph node metastases. Receiver operating characteristic (ROC) curve analysis was used to evaluate the efficacy of NLR, PLR and MLR in predicting poor prognosis of ESCC. Results: Univariate analysis showed that the degree of differentiation, the degree of invasion and the number of lymph node metastasis were related to the prognoses of patients with ESCC (P<0.05). Multivariate logistic regression analysis showed that the degree of differentiation, depth of invasion and number of lymph node metastases were independent influencing factors for poor prognosis of patients with ESCC, moderate differentiation (OR=2.603, 95% CI: 1.009-6.715) or low differentiation (OR=9.909, 95% CI: 3.097-31.706), infiltrating into fibrous membrane (OR=14.331, 95% CI: 1.333-154.104) or surrounding tissue (OR=23.368, 95% CI: 1.466-372.578), the number of lymph node metastases ≥ 3 (OR=9.225, 95% CI: 1.693-50.263) indicated poor prognosis. Spearman correlation analysis showed that NLR was negatively correlated with the degree of differentiation and the number of lymph node metastases (r=-0.281, P=0.001; r=-0.257, P=0.003), PLR was negatively correlated with the degree of differentiation, depth of invasion and number of lymph node metastasis (r=-0.250, P=0.004; r=0.197, P=0.025; r=-0.194, P=0.027), MLR was positively correlated with the degree of differentiation and the number of lymph node metastasis (r=0.248, P=0.004; r=0.196, P=0.025). ROC curve analysis showed that the areas under the curve of NLR, PLR and MLR in predicting poor prognosis of ESCC were 0.971, 0.925 and 0.834, respectively. The best cut-off value of NLR was 2.87. The sensitivity and specificity of NLR in predicting poor prognosis of ESCC were 90.6% and 87.9%, respectively. The optimal cut-off value of PLR was 141.75. The sensitivity and specificity for predicting poor prognosis of ESCC were 92.2% and 87.9%, respectively. The best cut-off value of MLR was 0.40. The sensitivity and specificity of MLR in predicting poor prognosis of esophageal squamous cell carcinoma were 54.7% and 100.0%, respectively. Conclusions: The degree of differentiation, the degree of invasion and the number of lymph node metastases are closely related to the poor prognosis of patients with esophageal squamous cell carcinoma. NLR, PLR and MLR can provide important information for predicting the poor prognosis of esophageal squamous cell carcinoma.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Prognóstico , Metástase Linfática/patologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Neutrófilos , Linfócitos , Plaquetas/patologia , Inflamação , Estudos Retrospectivos
12.
Zhonghua Yi Xue Za Zhi ; 103(18): 1429-1434, 2023 May 16.
Artigo em Chinês | MEDLINE | ID: mdl-37150697

RESUMO

Objective: To predict the protection probability of different clinical outcomes after reinfection with Omicron variant in symptomatic and unvaccinated COVID-19 patients who infected with prototype strain. Methods: The data used in this study were derived from a systematic review and meta-analysis which systematically searched PubMed, Embase, Web of Science, and Europe PMC databases, included published and uploaded studies of dynamic changes of neutralizing antibodies in symptomatic COVID-19 patients from 1 January 2020 to 2 October 2022 and extracted the literature information, study design, serological experiment information and antibody results. According to the scatter distribution characteristics of antibody titer data, a generalized additive model based on Gaussian distribution was used to fit the titer value of neutralizing antibody based on logarithmic conversion and the dynamic change pattern of neutralizing antibody in symptomatic and unvaccinated COVID-19 patients infected with prototype strain over time was obtained. In this study, the fitted antibody titers of patients on the 28th, 51st, and 261st day after symptom onset was selected to predict the protection probability. Results: Neutralizing antibodies produced in symptomatic and unvaccinated patients infected with prototype strain could provide protection against Omicron reinfection, and the probability of protection gradually decreased with time. Neutralizing antibody level on day 28 after symptom onset provided protection probability of 30.3% (95%CI: 20.0%-45.5%) against reinfection, 51.5% (95%CI: 33.4%-75.9%) against symptomatic reinfection, and 91.2% (95%CI: 77.1%-97.7%) against severe reinfection caused by Omicron BA.5. The protection probability against Omicron BA.1, BA.4 and BA.5 reinfections decreased significantly 261 days after symptom onset, showing 9.6%-12.9%, 18.4%-23.9% and 63.1%-70.3% against three clinical outcomes, respectively. At the same time point and against the same clinical outcome, the protection probability of BA.1 was the highest, followed by BA.4 and BA.5. Conclusions: Neutralizing antibodies induced in symptomatic and unvaccinated COVID-19 patients previously infected with the prototype strain have limited protection probability against Omicron BA.5 reinfections and symptomatic reinfections. The protection probability against Omicron BA.5 reinfections is 30.3% 28 days after symptom onset and decreases to about 10% after 261 days. However, the protection probability against severe reinfections is considerable, with over 90% 28 days after symptom onset and still exceeding 60% after 261 days.


Assuntos
COVID-19 , Reinfecção , Humanos , SARS-CoV-2 , Anticorpos Neutralizantes , Probabilidade , Anticorpos Antivirais
13.
Zhonghua Gan Zang Bing Za Zhi ; 31(11): 1209-1216, 2023 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-38238956

RESUMO

Objective: To extract the differentially expressed key genes of primary biliary cholangitis (PBC) using bioinformatics methods, so as to provide information for further study into the mechanism. Methods: The GSE119600 dataset was downloaded from the GEO database to obtain differentially expressed genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Protein-protein interaction (PPI) network reconstruction, Cytoscape software visualization, and core gene screening were performed. The area under the receiver operating characteristic curve (ROC AUC) was used to assess the diagnostic effectiveness of genes and plot the pROC software package. The x-Cell software was used to calculate the enrichment score of 34 immune cells in each sample. Finally, four key genes (PSMA4, PSMA1, PSMB1, and PSMA3) were selected. Blood samples were analyzed using the qPCR method. Results:: A total of 373 immune-related differentially expressed genes were identified. Eight genes (PSMC6, PSMB2, PSMB1, PSMA3, PSMA4, PSMA1, PSMD7, and PSMB5) were screened from the 178 nodes and 596 edges as hub genes of the PPI network, which were significantly related to amino acid metabolism, hematopoietic stem cell differentiation, cell cycle, and immune processes. PSMA4, PSMA1, PSMB1, and PSMA3 were defined as immunological biomarkers for PBC with an AUC value of the ROC curve > 0.7. Immunoinfiltrating cell analysis showed that the proportion of eosinophils was significantly higher in PBC patients compared to the control group, whereas the proportion of CD4+ memory T cells, plasma cells, Th2 cells, and cDC cells was significantly lower in PBC patients than the control group. Plasma cells were associated with all four immunological biomarkers. Seven PBC patients and seven healthy subjects were selected for peripheral blood qPCR validation, which demonstrates that PSMB1, PSMA3, PSMA1, and PSMA4 levels were significantly lower in PBC patients than healthy subjects, with a statistically significant difference. Conclusion:: Bioinformatics screened eight key genes, of which four were key immunological markers and may serve as a basis for clinical diagnosis and mechanism exploration.


Assuntos
Cirrose Hepática Biliar , Humanos , Ciclo Celular , Biologia Computacional , Bases de Dados Factuais , Biomarcadores , Perfilação da Expressão Gênica
14.
Zhonghua Jie He He Hu Xi Za Zhi ; 46(8): 829-834, 2023 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-37536996

RESUMO

Organoids are tissue cultures formed by culturing cells in three-dimensional environments that simulate the physiological or pathological conditions of the human body. The cultivation of organoids is used to study the temporal and spatial transformation of cells during the development of tissues or organs, to investigate changes in cellular functions and inter-communications caused by various risk factors, and to discover potential therapeutic targets. This article provided an overview of the cultivation and identification methods of alveolar organoids, as well as the research progress in their application to common respiratory diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease, viral pneumonia, and so on. The limitations and future applications of alveolar organoids are also analyzed and discussed.


Assuntos
Pneumopatias , Pneumonia Viral , Doença Pulmonar Obstrutiva Crônica , Humanos , Pulmão/patologia , Pneumopatias/patologia , Pneumonia Viral/patologia , Organoides/patologia , Organoides/fisiologia , Doença Pulmonar Obstrutiva Crônica/patologia
15.
Zhonghua Gan Zang Bing Za Zhi ; 31(6): 574-581, 2023 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-37400380

RESUMO

Objective: To compare the impact of different prognostic scores in patients with acute-on-chronic liver failure (ACLF) in order to provide treatment guidance for liver transplantation. Methods: The information on inpatients with ACLF admitted at Beijing You'an Hospital Affiliated to Capital Medical University and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2022 was collected retrospectively. ACLF patients were divided into liver transplantation and non-liver transplantation groups, and the two groups prognostic conditions were followed-up. Propensity score matching was carried out between the two groups on the basis of liver disease (non-cirrhosis, compensated cirrhosis, and decompensated cirrhosis), the model for end-stage liver disease incorporating serum sodium (MELD-Na), and ACLF classification as matching factors. The prognostic condition of the two groups after matching was compared. The difference in 1-year survival rate between the two groups was analyzed under different ACLF grades and MELD-Na scores. The independent sample t-test or rank sum test was used for inter-group comparison, and the χ (2) test was used for the comparison of count data between groups. Results: In total, 865 ACLF inpatients were collected over the study period. Of these, 291 had liver transplantation and 574 did not. The overall survival rates at 28, 90, and 360 days were 78%, 66%, and 62%, respectively. There were 270 cases of matched ACLF post-liver transplantation and 270 cases without ACLF, in accordance with a ratio of 1:1. At 28, 90, and 360 days, patients with non-liver transplantation had significantly lower survival rates (68%, 53%, and 49%) than patients with liver transplantation (87%, 87%, and 78%, respectively; P < 0.001). Patients were classified into four groups according to the ACLF classification criteria. Kaplan-Meier survival analysis showed that the survival rates of liver transplantation and non-liver transplantation patients in ACLF grade 0 were 77.2% and 69.4%, respectively, with no statistically significant difference (P = 0.168). The survival rate with an ACLF 1-3 grade was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.05). Patients with ACLF grades 1, 2, and 3 had higher 1-year survival rates compared to non-liver transplant patients by 50.6%, 43.6%, and 61.7%, respectively. Patients were divided into four groups according to the MELD-Na score. Among the patients with a MELD-Na score of < 25, the 1-year survival rates for liver transplantation and non-liver transplantation were 78.2% and 74.0%, respectively, and the difference was not statistically significant (P = 0.149). However, among patients with MELD-Na scores of 25-30, 30-35, and≥35, the survival rate was significantly higher in liver transplantation than that of non-liver transplantation, and the 1-year survival rate increased by 36.4%, 54.9%, and 62.5%, respectively (P < 0.001). Further analysis of the prognosis of patients with different ACLF grades and MELD-Na scores showed that ACLF grades 0 or 1 and MELD-Na score of < 30 had no statistically significant difference in the 1-year survival rate between liver transplantation and non-liver transplantation (P > 0.05), but in patients with MELD-Na score≥30, the 1-year survival rate of liver transplantation was higher than that of non-liver transplantation patients (P < 0.05). In the ACLF grade 0 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 77.8% and 25.0% respectively (P < 0.05); while in the ACLF grade 1 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 100% and 20.0%, respectively (P < 0.01). Among patients with ACLF grade 2, the 1-year survival rate with MELD-Na score of < 25 in patients with liver transplantation was 73.9% and 61.6%, respectively, and the difference was not statistically significant (P > 0.05); while in the liver transplantation patients group with MELD-Na score of ≥25, the 1-year survival rate was 79.5%, 80.8%, and 75%, respectively, which was significantly higher than that of non-liver transplantation patients (36.6%, 27.6%, 15.0%) (P < 0.001). Among patients with ACLF grade 3, regardless of the MELD-Na score, the 1-year survival rate was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.01). Additionally, among patients with non-liver transplantation with an ACLF grade 0~1 and a MELD-Na score of < 30 at admission, 99.4% survived 1 year and still had an ACLF grade 0-1 at discharge, while 70% of deaths progressed to ACLF grade 2-3. Conclusion: Both the MELD-Na score and the EASL-CLIF C ACLF classification are capable of guiding liver transplantation; however, no single model possesses a consistent and precise prediction ability. Therefore, the combined application of the two models is necessary for comprehensive and dynamic evaluation, but the clinical application is relatively complex. A simplified prognostic model and a risk assessment model will be required in the future to improve patient prognosis as well as the effectiveness and efficiency of liver transplantation.


Assuntos
Insuficiência Hepática Crônica Agudizada , Doença Hepática Terminal , Humanos , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
16.
Osteoarthritis Cartilage ; 30(3): 395-405, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34715366

RESUMO

Osteoarthritis (OA) is a multifactorial arthritic disease of weight-bearing joints concomitant with chronic and intolerable pain, loss of locomotion and impaired quality of life in the elderly population. Although the prevalence of OA increases with age, its specific mechanisms have not been elucidated and effective therapeutic disease-modifying drugs have not been developed. As essential organelles in chondrocytes, mitochondria supply energy and play vital roles in cellular metabolism, proliferation and apoptosis. Mitochondrial quality control (MQC) is the key mechanism to coordinate various mitochondrial biofunctions, primarily through mitochondrial biogenesis, dynamics, autophagy and the newly discovered mitocytosis. An increasing number of studies have revealed that a loss of MQC homeostasis contributes to the cartilage damage during the occurrence and development of OA. Several master MQC-associated signaling pathways and regulators exert chondroprotective roles in OA, while cartilage damage-related molecular mechanisms have been partially identified. In this review, we summarized known mechanisms mediated by dysregulated MQC in the pathogenesis of OA and latent bioactive ingredients and drugs for the prevention and treatment of OA through the maintenance of MQC.


Assuntos
Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Condrócitos/metabolismo , Mitocôndrias/metabolismo , Osteoartrite/metabolismo , Autofagia , Cartilagem Articular/efeitos dos fármacos , Regulação para Baixo , Humanos , Osteoartrite/tratamento farmacológico , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio , Regulação para Cima
17.
Opt Express ; 30(4): 4978-4987, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35209469

RESUMO

Due to the high intensity and MHz repetition rate of photon pulses generated by the European X-ray Free-Electron Laser, the heat load on silicon crystal monochromators can become large and prevent ideal transmission in Bragg diffraction geometry due to crystal deformation. Here, we present experimental data illustrating how heat load affects the performance of a cryogenically cooled monochromator under such conditions. The measurements are in good agreement with a depth-uniform model of X-ray dynamical diffraction taking beam absorption and heat deformation of the crystals into account.

18.
Osteoporos Int ; 33(9): 1937-1947, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35704055

RESUMO

The effectiveness of home-based resistance exercise in elder participants with osteoporosis remains unclear. This study demonstrates the beneficial effects of this mode of exercise on improving physical function, increasing confidence in exercise, and reducing fear of falling. INTRODUCTION: This study aims to evaluate the effect of a home-based resistance exercise (HBRE) program versus control on physical function, exercise self-efficacy, falling efficacy, and health-related quality of life (HRQOL). METHODS: This randomized controlled trial included 72 elderly participants with osteoporosis. Participants in the intervention group received a 12-week HBRE program, and the control group received usual care. The primary outcome was physical function, including muscle strength and balance ability; secondary outcomes were exercise self-efficacy, falling efficacy, and HRQOL. Within-group and between-group changes in outcome were evaluated by t-test and rank-sum test. RESULTS: A total of 68 subjects were included in the final analysis. Improvement in physical function was significantly greater in the HBRE group compared with controls. On a psychological level, exercise self-efficacy and falling efficacy improved significantly in the HBRE group; no significant change was observed in the control group. Most of the dimensions of HRQOL demonstrated improvements as well. The adherence was 85.29%, with no adverse events related to the exercise. CONCLUSION: A 12-week HBRE program was safe non-pharmacological therapy for elderly participants with osteoporosis, improving physical function, exercise self-efficacy, reduced fear of falling, and improved HRQOL. TRIAL REGISTRATION: Chinese Clinical Trial Register: ChiCTR2100051455. Registered 23.09.21. Retrospectively registered.


Assuntos
Osteoporose , Treinamento Resistido , Acidentes por Quedas/prevenção & controle , Idoso , Medo , Humanos , Osteoporose/terapia , Equilíbrio Postural , Qualidade de Vida , Treinamento Resistido/métodos , Treinamento Resistido/normas
19.
Phys Rev Lett ; 128(17): 174803, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35570446

RESUMO

We propose a new method for self-injection of high-quality electron bunches in the plasma wakefield structure in the blowout regime utilizing a "flying focus" produced by a drive beam with an energy chirp. In a flying focus the speed of the density centroid of the drive bunch can be superluminal or subluminal by utilizing the chromatic dependence of the focusing optics. We first derive the focal velocity and the characteristic length of the focal spot in terms of the focal length and an energy chirp. We then demonstrate using multidimensional particle-in-cell simulations that a wake driven by a superluminally propagating flying focus of an electron beam can generate GeV-level electron bunches with ultralow normalized slice emittance (∼30 nm rad), high current (∼17 kA), low slice energy spread (∼0.1%), and therefore high normalized brightness (>10^{19} A/m^{2}/rad^{2}) in a plasma of density ∼10^{19} cm^{-3}. The injection process is highly controllable and tunable by changing the focal velocity and shaping the drive beam current. Near-term experiments at FACET II where the capabilities to generate tens of kA, <10 fs drivers are planned, could potentially produce beams with brightness near 10^{20} A/m^{2}/rad^{2}.

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