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The performance appraisal of public hospitals is the most official and authoritative assessment and evaluation of tertiary public hospitals in China,and it is an important measure to guide hospitals to improve their internal management level and achieve high-quality development.In this study,a data monitoring management system based on the performance appraisal indicators of national tertiary public hospitals was developed and constructed through intelligent collection and reporting,report in-tegration,visual analysis,data drilling,etc.,which realized the one-stop dynamic management of indicators,optimized the data filling process of national examination indicators,improved the data quality and credibility,and promoted the integration of na-tional assessment and hospital assessment.the intelligent management level of the hospital has been improved,which provides strong support for the hospital's refined operation management and scientific decision-making.
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ObjectiveTo observe the effects of Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the Haizao Yuhutang (HYT) on oxidative stress in the liver of goiter rats under the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020. MethodA total of 128 male Wistar rats were randomly divided into a blank group, a model group, a euthyrox group (20 μg·kg-1), a HYT group (12.06 g·kg-1), a HYT without Sargassum (HYT-H) group (9.90 g·kg-1), a HYT without Glycyrrhizae Radix et Rhizoma (HYT-G) group (10.26 g·kg-1), a HYT without Sargassum and Glycyrrhizae Radix et Rhizoma (HYT-HG) group (8.10 g·kg-1), and a Sargassum and Glycyrrhizae Radix et Rhizoma (HG) group (3.96 g·kg-1). The blank group was given deionized water by gavage, and the others were given propylthiouracil (PTU) to replicate the goiter pathological model. Euthyrox was taken as a positive control drug, and the rest of the Chinese medicine groups were given the corresponding decoction by gavage, the material was collected 12 hours after the last dose. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), reactive oxygen species (ROS) in liver tissue were detected in each group. The pathological changes in the liver were observed via hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was utilized to detect the mRNA expressions of Kelch-like Ech-associated protein 1 (Keap1), nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), p53 and Caspase-3 in liver tissues. Western blot was adopted to detect the protein expressions of Nrf2 and HO-1 in liver tissues in oxidative stress-related signaling pathways. ResultCompared with control group, the model group showed significantly increased serum ALT level and contents of MDA and ROS in liver tissues (P<0.05, P<0.01), significantly reduced activities of SOD and GSH-Px in the liver (P<0.01), significantly increased mRNA expression of Keap1 (P<0.01), and significantly decreased mRNA and protein expressions of Nrf2 and HO-1 (P<0.05, P<0.01). Compared with the model group, the HYT group manifested significantly reduced serum levels of AST, ALT, and ALP (P<0.05, P<0.01), significantly reduced contents of MDA and ROS in liver tissue (P<0.01), significantly increased the activities of SOD and GSH-Px (P<0.01), significantly decreased mRNA expressions of Keap1, p53, and Caspase-3 (P<0.01), and significantly increased mRNA and protein expressions of Nrf2 and HO-1 (P<0.05, P<0.01). ConclusionUnder the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020, Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the HYT on oxidative stress in the liver of goiter rats had different effects. The HYT that contains Sargassum and Glycyrrhizae Radix et Rhizoma has a protective effect on the liver of goiter rats, and the effect is better than that of the HG group, the euthyrox group, and the incomplete groups. Its mechanism may be related to activating the Nrf2/HO-1 signaling pathway to alleviate liver oxidative stress and inhibiting the p53/Caspase-3 signaling pathway to reduce hepatocyte apoptosis.
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Objective:To investigate the clinical significances of evaluation indexes of right heart function injury in patients with BCR-ABL-negative myroproliferative neoplasms (MPN).Methods:The clinical data of 208 patients with BCR-ABL-negative MPN diagnosed in the Second People's Hospital of Lianyungang and Jiangsu Province Hospital from January 2015 to August 2021 were retrospectively analyzed, including 63 cases of primary myelopathic fibrosis (PMF), 39 cases of polycytosis vera (PV) and 106 cases of essential thrombocythemia (ET). The clinical characteristics of patients and the examination results of hematological related indicators were compared among the three groups. The examination results of indexes of right heart function injury were analyzed, including echocardiography, brain natriuretic peptide, soluble growth stimulation expression gene-2 (sST-2), lactate dehydrogenase (LDH), D-dimer, ferritin, β 2-microglobulin, peripheral blood WT1 gene, CD34 + cell count, etc. Results:Of the 208 patients, 109 were male and 99 were female; the median age was 62 years old (23 years old, 89 years old). The differences in levels of hemoglobin, platelet count, D-dimer, LDH and ferritin among PMF, PV and ET patients were statistically significant (all P < 0.05). Color echocardiography was performed in 87 patients, including 26 cases of PMF, 19 cases of PV and 42 cases of ET. Pulmonary artery pressure increased in 69 cases (79.3%), left atrial diameter increased in 76 cases (87.3%), and diameter increased during right ventricular diastolic period in 59 cases (67.8%). There were significant differences in pulmonary artery pressure, left atrial diameter and diameter during right ventricular diastolic period among PMF, PV and ET patients (all P < 0.05). Pearson correlation analysis showed that pulmonary artery pressure was positively correlated with ferritin, LDH, sST-2 and age ( r values were 0.796, 0.768, 0.915 and 0.734, all P<0.05), while it was negatively correlated with platelet count ( r = -2.330, P = 0.034). Conclusions:For BCR-ABL-negative MPN patients, the increase of pulmonary artery pressure, ferritin and LDH and the decreased platelet count and hemoglobin may increase the probability of right heart function impairment. For BCR-ABL-negative MPN patients with the higher levels of ferritin, LDH, sST-2, age, and the lower level of platelet count, the pulmonary artery pressure may be higher.
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Objective:To explore the material basis and mechanism of Linggui Zhugan Decoction in treating hypertension and obesity by means of network pharmacology and molecular docking technique.Methods:The TCMSP was retrieved and the main active components and action targets of Linggui Zhugan Decoction were screened. The GeneCards, OMIM, TTD, DisGeNET and DrugBank databases were used to screen disease-related targets of hypertension and obesity. The Cytoscape 3.9.0 was used to draw Chinese materia medica-composition-intersection target-disease network diagram. The STRING 11.5 database was used to draw PPI network. The cytoNCA plug-in was used to screen core active components and targets. The bioenrichment analysis of GO and KEGG was carried out in the R4.1.2, and the Chinese materia medica-intersection target-path diagram was drawn, and the core active components and core targets were docked in PyMOL and AutoDockTools 1.5.7.Results:A total of 102 potentially active components and 62 intersection targets were obtained, and 8 active components and 7 core targets were screened. Enrichment analysis showed that the key targets were mainly enriched through the signaling pathways of fluid shear stress and atherosclerosis, lipid and atherosclerosis, and AGE-RAGE, which were involved in biological processes such as the response to nutritional levels and the regulation of small molecule metabolism. Molecular docking showed that there were 37 groups with addinity < -7 kcal/mol.Conclusion:The main active components of Linggui Zhugan Decoction are quercetin, kaempferol and naringenin, which may play a role in fluid shear stress and atherosclerosis pathway, lipid and atherosclerosis pathway and AGE-RAGE signal pathway through AKT1, EGFR, IL1B and other targets.
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The clinical symptoms of myasthenia gravis (MG) in women are closely related to pregnancy, and the outcome of pregnancy and neonates is related to MG disease control, comorbidities and antibody types. The exacerbation of muscle weakness usually appeared in the first trimester and postpartum 0-3 months. The adverse pregnancy outcomes of MG mothers are mainly fetal arrest and abortion. Neonatal muscle weakness and congenital joint flexion are common neuromuscular lesions in childbirth. During pregnancy, the immune system of MG pregnant women is regulated by estrogen/progesterone/prolactin/glucocorticoid, and the main result is to inhibit pro-inflammatory response and promote immune tolerance. However, the specific interaction between MG and pregnancy remains to be elucidated in prospective cohort studies.
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In the electroencephalography (EEG) monitoring of patients with hypoxic-ischemic encephalopathy, generalized periodic discharges are often monitored abnormal waveforms. When there are some features of generalized periodic discharges (e.g., frequency≥1.5 Hz or plus), it indicates that the patient is at high risk for seizures or has a poor prognosis. Compared with conventional EEG, the time of continuous EEG monitoring is longer, so the detection rate of these waveforms is higher. At present, scholars at home and abroad have studied these waveforms, but there is controversy about the significance of these waveforms. In this paper, the definition and characteristics of these waveforms and their significance in determining prognosis and guiding treatment in patients with hypoxic-ischemic encephalopathy are reviewed.
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Rheumatoid arthritis (RA) is a refractory autoimmune disease that can cause symmetrical polyarticular disease. The key mechanism of its occurrence and development is the dysequilibrium of helper T cell 17 (Th17)/regulatory T cell (Treg) balance. Therefore, reconstructing Th17/Treg balance may be a new strategy for the treatment of RA. Traditional Chinese medicine has significant advantages in the treatment of RA such as integrity, multi-target, multi-link and multi-path. This paper summarizes the basic and clinical studies on the regulation of Th17/Treg balance in the treatment of RA by traditional Chinese medicine in the past five years, and finds that the active components/sites of traditional Chinese medicine such as flavonoids, alkaloids and terpenes have unique advantages in the regulation of Th17/Treg balance. The traditional Chinese medicine compound formula interferes with Th17/Treg balance by exerting the effects of dispelling wind, dehumidifying, removing blood stasis, unblocking collaterals, relieving pain, dispersing cold and strengthening health. The effect of external treatment of traditional Chinese medicine is obvious and can be used as a clinical adjuvant therapy for RA; related mechanisms of action include regulating the production of inflammatory factors, regulating the expression of transcription factors and interfering with the activation of signaling pathways. However, the existing research has the shortcomings of insufficient mechanism research, few clinical research, limited external treatment research of traditional Chinese medicine, and lack of combination therapy research, which need to be improved by follow- up research.
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BACKGROUND@#This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability.@*METHODS@#This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability.@*RESULTS@#STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min.@*CONCLUSION@#The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
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Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Guias de Prática Clínica como AssuntoRESUMO
Cancer immunotherapy has become a promising strategy. However, the effectiveness of immunotherapy is restricted in "cold tumors" characterized with insufficient T cells intratumoral infiltration and failed T cells priming. Herein, an on-demand integrated nano-engager (JOT-Lip) was developed to convert cold tumors to hot via "increased DNA damage and dual immune checkpoint inhibition" strategy. JOT-Lip was engineered by co-loading oxaliplatin (Oxa) and JQ1 into liposomes with T-cell immunoglobulin mucin-3 antibodies (Tim-3 mAb) coupled on the liposomal surface by metalloproteinase-2 (MMP-2)-sensitive linker. JQ1 inhibited DNA repair to increase DNA damage and immunogenic cell death (ICD) of Oxa, thus promoting T cells intratumoral infiltration. In addition, JQ1 inhibited PD-1/PD-L1 pathway, achieving dual immune checkpoint inhibition combining with Tim-3 mAb, thus effectively promoting T cells priming. It is demonstrated that JOT-Lip not only increased DNA damage and promoted the release of damage-associated molecular patterns (DAMPs), but also enhanced T cells intratumoral infiltration and promoted T cell priming, which successfully converted cold tumors to hot and showed significant anti-tumor and anti-metastasis effects. Collectively, our study provides a rational design of an effective combination regimen and an ideal co-delivery system to convert cold tumors to hot, which holds great potential in clinical cancer chemoimmunotherapy.
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Objective:To investigate the clinical features and influencing factors of long-term prognosis of tuberculous meningitis(TBM), and to provide a recommendation for treatment and early intervention of TBM.Methods:Clinical data of TBM patients were retrospectively collected at Peking Union Medical College Hospital from January 2014 to December 2021. Patients who were followed-up more than one year were divided into two groups according to modified Rankin Scale (mRS). Risk factors associated with long-term prognosis were analyze by conditional logistic stepwise regression.Results:A total of 60 subjects were enrolled including 33 (55%) males and 27 (45%) females with age 15-79 (44.5±19.8) years. There were 30 cases (50%) complicated with encephalitis, 21 cases (35%) with miliary tuberculosis. The diagnosis was microbiologically confirmed in 22 patients (36.7%), including 5 cases (22.7%, 5/22) by acid-fast staining, 8 cases (36.4%, 8/22) by Mycobacterium tuberculosis (MTB) culture, and 20 cases (90.9%, 20/22) by molecular biology. The median follow-up period was 52(43, 66 ) months in 55 cases surviving more than one year. Among them, 40 cases (72.7%) were in favorable group (mRS 0-2) and 15 cases (27.3%) were in unfavorable group (mRS 3-6) with poor prognosis. The mortality rate was 20% (11/55). Elderly ( OR=1.06, P=0.048 ) , hyponatremia( OR=0.81, P=0.020), high protein level in cerebrospinal fluid (CSF) ( OR=3.32, P=0.033), cerebral infarction( OR=10.50, P=0.040) and hydrocephalus( OR=8.51, P=0.049) were associated with poor prognosis in TBM patients. Conclusions:The mortality rate is high in patients with TBM. Molecular biology tests improves the sensitivity and shorten the diagnosis time of TBM. Elderly, hyponatremia, high protein level in CSF, cerebral infarction and hydrocephalus are independent risk factors of long-term survival in TBM patients.
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Objective:To analyze the clinical features of patients with infective endocarditis (IE) and to improve the awareness of this disease.Methods:A total of 425 IE patients hospitalized in Peking Union Medical College Hospital from January 2011 to December 2018 were included in this study. The clinical features, predisposing cardiac diseases, pathogens and outcomes were retrospectively analyzed. The binary logistic regression model was adopted to analyze the risk factors.Results:Among 425 IE patients, the median period from onset of disease to diagnosis was 10 weeks. Fever (423 cases, 99.5%) and cardiac murmur (372 cases, 87.5%) were the most common clinical manifestations. Congestive heart failure (219 cases, 51.5%) and embolism (158 cases, 37.2%) were the most common complications. Two hundred and fifty (58.8%) patients had predisposing cardiac diseases with congenital heart diseases (121 cases, 28.5%) as the leading cause. Vegetations were found in 410(96.5%) patients through echocardiography and surgery. Totally 343(80.7%) patients got a positive pathogen test with Streptococcus viridans accounted for 59.5%(204/343) as the major pathogen of IE.All 425 patients received antimicrobial therapy, 342(80.5%) patients received surgery, among them 332 cases (97.1%) were early surgery, and the in-hospital mortality rate was 4.5%(19/425). Logistic regression analysis showed that New York heart function assessment Ⅲ/Ⅳ (odds ratio ( OR)=3.40, 95% confidence interval ( CI) 1.30 to 11.68), cerebral embolism ( OR=4.45, 95% CI 1.50 to 13.22) and septic shock ( OR=19.41, 95% CI 3.81 to 99.02) were independent risk factors for in-hospital death(all P<0.050), while surgery was an independent protective factor against in-hospital death ( OR=0.15, 95% CI 0.05 to 0.47, P=0.001). Conclusions:There is still a significant delay in the diagnosis of IE. Physicians should be alert to IE. Multiple sets of blood cultures should be obtained before administration of antibiotics, and echocardiography should be performed in all patients with suspected IE as soon as possible. Bactericidal antimicrobial therapy and early surgery in patients with indications are critical aspects in the management of IE patients.
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Tumor tissue is a complex of tumor cells, stromal cells, and extracellular matrix, and they constitute a disordered and aggressive microenvironment, which plays an indispensable role in the occurrence and development of tumors. In breast cancer, cancer-associated fibroblasts (CAF) not only promote the occurrence, proliferation, invasion, metastasis, and drug resistance of tumor, but also participate in events including angiogenesis, lymph angiogenesis, extracellular matrix remodeling, and reconstruction of the microenvironment, which are known to induce cancer. Therefore, a new strategy for tumor therapy is provided by targeting CAF. This article reviews the research progress of CAF in breast cancer.
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Influenza virus is one of the common pathogens causing acute respiratory infectious diseases, and is easy to cause acute respiratory distress syndrome (ARDS) after infecting human body, which is an important cause of death of influenza patients. Influenza-induced ARDS results from a combination of overwhelming inflammation and immune response, causing tissue damage and apoptosis. Furthermore, virus-mediated oxidative stress is another important mechanism. Viral infection can produce excessive reactive oxygen species, which damage the epithelial-endothelial barrier with pulmonary edema. In this content, numerous studies have highlighted the importance of antioxidants as a new therapy aimed at blocking both viral replication and virus-induced inflammation. Therefore, this paper summarizes the epidemiology and mechanisms of influenza-induced ARDS, the role of oxidative stress in the occurrence and development of influenza-related ARDS and the role of antioxidants in anti influenza virus infection, in order to provide reference for effective treatment of influenza patients, reducing mortality, developing new anti influenza drugs and preventing and controlling influenza epidemic.
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@#Bromodomain-containing protein 4 (BRD4), a new target for tumor therapy, is the most important member of the bromodomain and extra-terminal family. The overexpression of BRD4 is associated with genesis and development of various cancers.Used either alone or in combination with other treatments such as chemotherapy, photothermal therapy and immunotherapy, the BRD4 inhibitors or degraders exhibited excellent antitumor effects, providing a new direction in tumor treatment. In this review, the structure and function of BRD4, the inhibition strategies of BRD4, the application in tumor combination therapy and drug resistance are introduced, which provides reference for targeting BRD4 in tumor therapy.
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Objective:To investigate the changes of related indicators of right heart hypofunction in patients with primary myelofibrosis (PMF).Methods:The clinical data of 55 PMF patients in the Second People's Hospital of Lianyungang in Jiangsu Province and Jiangsu Province Hospital from January 2015 to August 2019 were retrospectively analyzed. The differences in right heart function-related echocardiographic indexes and biochemical indexes between pre-fibrosis/early stage fibrosis patients and obvious stage fibrosis patients were compared. Single factor linear regression method was used to analyze the correlations of pulmonary artery pressure with biochemical indexes.Results:The hemoglobin level [119 g/L (47-224 g/L) vs. 78 g/L (33-182 g/L)] and platelet count [233×10 12/L (5×10 12/L-984×10 12/L) vs. 117×10 12/L (7×10 12/L-731×10 12/L)] of patients in the pre-fibrosis/early stage fibrosis group were higher than those in the obvious stage fibrosis group, and the differences were statistically significant (both P<0.05). Among 22 patients with complete results of cardiac ultrasound, 90.9% (20/22) patients had increased pulmonary artery pressure, 72.7% (16/22) patients had increased left atrial diameter, and 90.9% (20/22) patients had increased right ventricular diastolic diameter. There were no patients with abnormal ejection fraction. The pulmonary artery pressure [48 mmHg (46-90 mmHg) vs. 33 mmHg (20-50 mmHg) (1 mmHg = 0.133 kPa)], left ventricular diastolic diameter [46 mm (36-50 mm) vs. 47 mm (43-53 mm)] and fractional shortening rate [38.1% (36.0%-38.9%) vs. 35.4% (32.7%-37.8%)] of patients in the pre-fibrosis/early stage fibrosis group were higher than those in the obvious stage fibrosis group, and the differences were statistically significant (all P < 0.05). The pulmonary artery pressure of patients had positive correlations with age ( r = 0.590), serum ferritin (SF) ( r = 0.608), lactate dehydrogenase (LDH) ( r = 0.711) and soluble growth-stimulating expression gene 2 (ST-2) ( r = 0.580)(all P<0.05), and had negative correlation with platelet count ( r = -0.596, P = 0.003). Conclusion:PMF patients are prone to right heart hypofunction, the pulmonary artery pressure is higher in older patients and patients with high SF, LDH and ST-2 levels and low platelet count.
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Objective:To investigate the incidence and risk factors of human cytomegalovirus (HCMV) reactivation in immunocompetent severe pneumonia patients with mechanical ventilation and their effects on clinical outcomes.Methods:A prospective observational study was conducted. Forty-eight immunocompetent patients requiring invasive mechanical ventilation due to severe pneumonia in the department of critical care medicine of the First Affiliated Hospital of Guangzhou Medical University from June 30th, 2017 to July 1st, 2018 were enrolled. Meanwhile, all cases were followed up until 90 days after inclusion and were required to quantitatively detect HCMV DNA in serum at regular weekly intervals until 28 days after transferring to intensive care unit (ICU). Patients were divided into HCMV reactivation group (≥5×10 5 copies/L) and non-reactivation group (<5×10 5 copies/L) based on HCMV DNA at any time point within 28 days. Demographic data, basic indicators, respiratory indicators, disease severity scores, laboratory indicators, complication and clinical outcomes of the two groups were collected and analyzed. Multivariate Logistic regression analysis was performed to screen independent risk factors for HCMV reactivation. Results:All 48 subjects were tested positive for HCMV immunoglobulin G (IgG), so HCMV seropositive rate was 100%. HCMV reactivation occurred in 10 patients within 28 days after admission to ICU, and the reactivation incidence of HCMV was 20.83%. There was no significant difference in gender, age, body mass index (BMI), underling disease reasons for ICU transfer (except sepsis), basic vital signs, disease severity scores, or laboratory findings including infection, immune, blood routine, liver, kidney and circulatory indicators except neutrophils count (NEU), hypersensitivity C-reactive protein(hs-CRP), hemoglobin (Hb), blood urea nitrogen (BUN), N-terminal pro-brain natriuretic peptide (NT-proBNP) between the two groups. The height (cm: 160±6 vs. 166±8), body weight (kg: 49.4±11.2 vs. 57.6±10.5), Hb (g/L: 87±18 vs. 104±24) in HCMV reactivation group were significantly lower than non-reactivation group, as well as NEU [×10 9/L:12.7 (9.9, 22.5) vs. 8.9 (6.2, 13.8)], hs-CRP [mg/L: 115.5 (85.2, 136.6) vs. 39.9 (17.5, 130.2)], BUN [mmol/L:13.7 (8.9, 21.5) vs. 7.1 (4.9, 10.5)] and NT-proBNP [ng/L: 6 751 (2 222, 25 449) vs. 1 469 (419, 4 571)] within 24 hours of admission to ICU. The prevalence of sepsis [60.0% (6/10) vs. 15.8% (6/38)], blood transfusion [100.0% (10/10) vs. 60.5% (23/38)], hospitalization expense [ten thousand yuan: 35.7 (25.3, 67.1) vs. 15.2 (10.4, 22.0)], 90-day all-cause mortality [70.0% (7/10) vs. 21.1% (8/38)], length of ICU stay [days: 26 (16, 66) vs. 14 (9, 19)], the duration of mechanical ventilation [days: 26 (19, 66) vs. 13 (8, 18)] in HCMV reactivation group were significantly higher than non-reactivation group, and there were significant statistical differences between the two groups (all P < 0.05). Logistic regression analysis showed that sepsis was an independent risk factor for HCMV reactivation in immunocompetent mechanical ventilation severe pneumonia patients with mechanical ventilation [odds ratio ( OR) = 9.35, 95% confidence interval (95% CI) was 1.72-50.86, P = 0.010]. Conclusions:HCMV infection is very common in immunocompetent severe pneumonia patients on mechanical ventilation and incidence of HCMV reactivation is high. Moreover, HCMV reactivation could adversely affect clinical prognoses, and sepsis may be a risk factor for HCMV reactivation.
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Objective:To explore whether prophylactic anti-viral therapy is needed for hepatitis B virus (HBV) infection resolvers with high titer of hepatitis B surface antibody (anti-HBs) receiving rituximab treatment.Methods:This study was a prospective cohort study. Nine patients with hepatitis B surface antigen(HBsAg) negative/hepatitis B core antibody (anti-HBc) positive/anti-HBs positive receiving rituximab treatment in Chinese Academy of Medical Science, Peking Union Medical College Hospital from June 2017 to June 2018 were enrolled. Patients were divided into two groups according to baseline anti-HBs titers. Patients with anti-HBs≥100 mIU/mL did not receive prophylactic treatment after informed consent. Patients with anti-HBs<100 mIU/mL were prescribed with entecavir before the treatment of rituximab. All patients were followed up every month after the first use of rituximab. Liver function, HBV DNA and HBV serology markers were tested. Descriptive statistical analysis was used.Results:Of the nine patients, six patients were diagnosed with diffuse large B cell lymphoma (DLBCL), one with Waldenstrom′s macroglobulinemia, one with indolent B-cell lymphoma, and one with membranous nephropathy. There were seven patients with anti-HBs≥100 mIU/mL who did not receive prophylactic anti-HBV therapy, and two patients with anti-HBs<100 mIU/mL who received entecavir (0.5 mg/d) prophylactic treatment before chemotherapy. The anti-HBs titer of the patient with indolent B cell lymphoma decreased from 21.27 mIU/mL to 6.33 mIU/mL during the third course of rituximab treatment. After the fourth course of treatment, the anti-HBs titer of one patient with DLBCL decreased from 172.25 mIU/mL to 57.76 mIU/mL. One patient with membranous nephropathy was followed up for one year and the anti-HBs titer increased from 141.47 mIU/mL to 328.98 mIU/mL.No significant changes of anti-HBs titer were observed in other patients. No HBV reactivation occurred in all patients and HBV DNA remained negative during the follow-up.Conclusions:The anti-HBs titer may drop after rituximab treatment in resolved HBV patients. High titer of anti-HBs may protect resolved HBV patients from HBV reactivation. Patients with high titer of anti-HBs may not need prophylactic anti-viral therapy.
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BACKGROUND@#Differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) has been a challenge for clinicians in high TB burden countries. The purpose of this study was to improve the accuracy of differential diagnosis of ATB and LTBI by using fluorescent immunospot (FluoroSpot) assay to detect specific Th1 cell immune responses. The novel mycobacterium tuberculosis (MTB) latency-associated antigens Rv1733c and synthetic long peptides derived from Rv1733c (Rv1733c SLP) were used based on virulence factors early secreting antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10).@*METHODS@#Fifty-seven ATB cases, including 20 pathogen-confirmed ATB and 37 clinically diagnosed ATB, and 36 LTBI cases, were enrolled between January and December 2017. FluoroSpot assay was used to detect the interferon γ (IFN-γ) and interleukin 2 (IL-2) secreted by the specific T cells after being stimulated with MTB virulence factors ESAT-6 and CFP-10, MTB latency-associated antigens Rv1733c and Rv1733c SLP. The receiver operating characteristic (ROC) curve was used to define the best cutoff value of latency-associated antigens in the use of differentiating ATB and LTBI. The sensitivity, specificity, predictive value, and likelihood ratio of ESAT-6 and CFP-10-FluoroSpot combined with latency-associated antigen in the differential diagnosis of ATB and LTBI were also calculated.@*RESULTS@#Following the stimulation with Rv1733c and Rv1733c SLP, the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP had the largest area under the ROC curve, which was 0.766. With a cutoff value of 1 (spot-forming cells [SFCs]/2.5 × 105 peripheral blood mononuclear cells) for frequency, the sensitivity and specificity of distinguishing ATB from LTBI were 72.2% and 73.7%, respectively. ESAT-6 and CFP-10-FluoroSpot detected the frequency and proportion of single IFN-γ-secreting T cells; the sensitivity and specificity of distinguishing ATB from LTBI were 82.5% and 66.7%, respectively. Combined with the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP on the basis of ESAT-6 and CFP-10-FluoroSpot, the sensitivity and specificity increased to 84.2% and 83.3%, respectively.@*CONCLUSION@#Rv1733c SLP, combined with ESAT-6 and CFP-10, might be used as a candidate antigen for T cell-based tuberculosis diagnostic tests to differentiate ATB from LTBI.
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Humanos , Antígenos de Bactérias , Diagnóstico Diferencial , Tuberculose Latente/diagnóstico , Leucócitos Mononucleares , Mycobacterium tuberculosis , Tuberculose/diagnósticoRESUMO
Thrombocytopenia is the main clinical manifestation or common complication of multiple diseases, but there is still a lack of systematic understanding of pathogenesis, underlying diseases and treatment strategies of thrombocytopenia. Based on evidence-based medicine, this consensus summarizes seven aspects related to thrombocytopenia, including definition, epidemiology, pathogenesis, clinical manifestations, laboratory examination, diagnosis and treatment. This consensus provides an important reference for the diagnosis and treatment of thrombocytopenia.
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Objective:To improve the cognition of T-cell large granular lymphocytic leukemia (T-LGLL) combined with pure red cell aplasia (PRCA).Methods:The clinical characteristics, peripheral blood and bone marrow laboratory indicators of 14 newly diagnosed patients with T-LGLL combined with PRCA who were admitted to the Second People's Hospital of Lianyungang Affiliated to Bengbu Medical College and the People's Hospital of Jiangsu Province from August 2010 to October 2019 were retrospectively analyzed.Results:Among the 14 patients, there were 7 males and 7 females, with a median age of 58.5 years (33-75 years). At the first visit, the median white blood cell count was 5.02×10 9/L [(1.45-8.49)×10 9/L], the median absolute value of neutrophils was 1.35×10 9/L [(0.43-7.16)×10 9/L], the median lymphocyte ratio was 0.49 (0.13-0.77), the median hemoglobin was 58 g/L (42-106 g/L), the median red blood cell count was 2.01×10 12/L [(0.99-3.20)×10 12/L], the median reticulocyte count percentage was 0.52 (0.14-3.02), the median platelet was 96×10 9/L [(38-281)×10 9/L], the median large granular lymphocytes accounted for 71% (32%-81%) of lymphocytes. Bone marrow aspiration showed that the median large granular lymphocytes accounted for 0.16 (0.08-0.41) of nuclear cells, and the median serum β 2 microglobulin was 4.85 mg/L (2.81-7.22 mg/L). Two patients had ASXL1 and TET2 mutations, and one of them had STAT3, EP300 and FAM46C mutations. Six patients were T cell receptor (TCR) β and γ-positive, 1 patient were TCRβ-positive, 4 patients were TCRγ-positive, 1 patient was TCRδ-positive, 1 patient was TCRβ, γ and δ-positive, and 1 patient was all negative. Eight cases received cyclosporine therapy, 6 cases were effective; 6 cases received methotrexate combined with hormone therapy, 3 cases were effective. The initial induction therapy was effective in 9 cases, 5 patients who failed in the initial treatment received salvage treatment, and 2 cases were effective. Conclusions:The laboratory characteristics of patients with T-LGLL combined with PRCA are similar to those of simple T-LGLL, anemia is a prominent manifestation accompanied by neutropenia or thrombocytopenia. The large granular lymphocytes are easily seen in peripheral blood and bone marrow, and T monoclonal rearrangement of lymphocytes is an important feature, and the patients respond well to immunosuppressive therapy.