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Background The high degree of heterogeneity brought great challenges to the diagnosis and treatment of acute myeloid leukemia (AML). Although several different AML prognostic scoring models have been proposed to assess the prognosis of patients, the accuracy still needs to be improved. As important components of the tumor microenvironment, immune cells played important roles in the physiological functions of tumors and had certain research value. Therefore, whether the tumor immune microenvironment (TIME) can be used to assess the prognosis of AML aroused our great interest. Methods The patients’ gene expression profile from 7 GEO databases was normalized after removing the batch effect. TIME cell components were explored through Xcell tools and then hierarchically clustered to establish TIME classification. Subsequently, a prognostic model was established by Lasso-Cox. Multiple GEO databases and the Cancer Genome Atlas dataset were employed to validate the prognostic performance of the model. Receiver operating characteristic (ROC) and the concordance index (C-index) were utilized to assess the prognostic efficacy. Results After analyzing the composition of TIME cells in AML, we found infiltration of ten types of cells with prognostic significance. Then using hierarchical clustering methods, we established a TIME classification system, which clustered all patients into three groups with distinct prognostic characteristics. Using the differential genes between the first and third groups in the TIME classification, we constructed a 121-gene prognostic model. The model successfully divided 1229 patients into the low and high groups which had obvious differences in prognosis. The high group with shorter overall survival had more patients older than 60 years and more poor-risk patients (both P Conclusion A prognostic model for AML based on the TIME classification was constructed in our study, which may provide a new strategy for precision treatment in AML.

To evaluate the efficacy and risk of cataract surgery (phacoemulsification with intraocular lens [IOL] implantation) combined with endoscopic goniosynechialysis (EGSL) for advanced primary angle-closure glaucoma (PACG).Retrospective, continuous case series.A total of 16 patients (18 eyes) with advanced PACG were enrolled in this study between February 2014 and March 2016. Advanced glaucoma inclusion criteria were based on the method proposed in the Advanced Glaucoma Intervention Study, with a visual field score of 18 points or more.All patients underwent cataract surgery with EGSL by the same experienced surgeon. Paired t test and generalized estimating equation analyses were performed.The extent of peripheral anterior synechiae (PAS), number of intraocular pressure (IOP)-lowering drugs, IOP, best-corrected visual acuity (BCVA), and visual fields before and after surgery. The incidence of complications was recorded.The mean follow-up duration was 13.8 months (standard deviation, 2.7 months). The mean difference (preoperative minus postoperative) in PAS was 202.7° (95% confidence interval [CI], 43.5°). The mean difference (preoperative minus postoperative) in the number of IOP-lowering drugs and IOP was 2.0 (95% CI, ±0.5), and 9.4 mmHg (95% CI, ±2.1 mmHg) respectively. The mean improvement in BCVA was 0.29 logMAR (95% CI, ±0.14). A positive correlation was found between the extent of postoperative PAS and postoperative IOP (B = 8.2; P0.001) and also between postoperative PAS and postoperative number of IOP-lowering drugs (B = 28.9; P0.001). Anterior chamber hemorrhage and exudation occurred in 4 patients and 2 patients, respectively, after surgery. Posterior capsular opacification occurred in 5 patients after surgery.Cataract surgery with EGSL could be an effective surgical method for the treatment of advanced PACG.

Background: Pulmonary arterial hypertension (PAH) is a severe and fatal clinical syndrome characterized by high blood pressure and vascular remodeling in the pulmonary arterioles, which is also a rapidly progressing disease of the lung vasculature with a poor prognosis. Although PAH medication made great advances in recent years, the efficacy and safety of the medication are unsatisfactory. Therefore, we aimed to update and expand previous studies to explore the efficacy and safety of PAH-targeted medications. Methods: Relevant articles were searched and selected from published or publicly available data in PubMed, Cochrane Library, CNKI, PsycInfo, and MEDLINE (from inception until October 1st, 2020). To assess the efficacy and safety of PAH therapies, five efficacy outcomes [6-minute walking distance (6MWD), mean pulmonary arterial pressure (mPAP), WHO functional class (WHO FC) improvement, clinical worsening, death] and two safety outcomes [adverse events (AEs), serious adverse events (SAEs)] were selected. And 6MWD was regarded as the primary efficacy outcome. Results: 50 trials included with 10 996participants were selected. In terms of efficacy, all targeted drugs were more effective than placebo. For 6MWD, Bosentan + Sildenafil, Sildenafil, Bosentan + Iloprost were better than others. Bosentan + Iloprost and Bosentan + Sildenafil were better for mPAP. Bosentan + Iloprost and Ambrisentan + Tadalafil were more effective in improving WHO FC. Bosentan + Tadalafil and Bosentan + Iloprost had the Ambrisentan probability to reduce the incidence of clinical worsening. It is demonstrated that Ambrisentan had clear benefits in reducing all-cause mortality. In terms of safety, no therapies had been shown to reduce the incidence of SAEs significantly, and Ambrisentan + Tadalafil significantly increased the incidence of AEs. Conclusions: Phosphodiesterase 5 inhibitor (PDE5i) + Endothelin Receptor Antagonists (ERA) seems to be better therapy for PAH. Prostacyclin analogs (ProsA) + ERA appear promising, though additional data is warranted. Registration PROSPERO CRD42020218818.

To investigate the changes and evaluate the diagnosis value of circumpapillary vessel density (VD) in cases of acute primary angle closure (APAC).Case-control study.APAC patients with a history of unilateral acute attack were enrolled. The eyes with acute episode constituted the case group while the contralateral eyes without attack consisted of the control group. Ophthalmic examinations including slit-lamp examination, best-corrected visual acuity, intraocular pressure and visual field were carried out. Retinal nerve fiber layer (RNFL), macular ganglion cell complex (GCC) were measured by spectral-domain optical coherence tomography, while VD was assessed by optical coherence tomography angiography.The whole en face image vessel density (wiVD), circumpapillary vessel density (cpVD) and inside disk VD for both all vessels and capillary were all significantly lower in the APAC eyes compared to the fellow eyes (P 0.01 for all). In APAC eyes, the wiVD, inside disk VD and cpVD both for all vessels and capillary were all positively correlated with RNFL and GCC thicknesses but negatively correlated with the mean deviation (MD), pattern standard deviation (PSD) and the duration of acute attack (all P 0.01). From the ROC curve, the cpVDIn APAC eyes, circumpapillary VD decreased significantly compared with the fellow unaffected eyes. They were significantly correlated with thicknesses of RNFL and GCC, and visual field MD and PSD in the APAC eyes. The patients with longer duration of acute attack were more likely to have lower cpVD. For APAC, the diagnostic ability of wiVD and cpVD was similar with RNFL, GCC and MD and was higher than inside disk VD.

Vitamin D deficiency is associated with increased risks of chronic obstructive pulmonary disease (COPD). Nevertheless, the mechanisms remain unknown. This study analyzed the correlations between vitamin D levels and inflammation in COPD patients. One hundred and one patients with COPD and 202 control subjects were enrolled. Serum 25(OH)D level and inflammatory cytokines were detected. Serum 25(OH)D was decreased and inflammatory cytokines were increased in COPD patients. According to forced expiratory volume in 1 s, COPD patients were divided into three grades. Furthermore, serum 25(OH)D was gradually decreased in COPD patients ranging from grade 1–2 to 4. Serum 25(OH)D was inversely associated with inflammatory cytokines in COPD patients. Further analysis found that NF-κB and AP-1 signaling were activated in COPD patients. Besides, inflammatory signaling was gradually increased in parallel with the severity of COPD. By contrast, pulmonary nuclear vitamin D receptor was decreased in COPD patients. In vitro experiments showed that 1,25(OH)2D3 inhibited LPS-activated inflammatory signaling in A549 cells (human lung adenocarcinoma cell). Mechanically, 1,25(OH)2D3 reinforced physical interactions between vitamin D receptor with NF-κB p65 and c-Jun. Our results indicate that vitamin D is inversely correlated with inflammatory signaling in COPD patients. Inflammation may be a vital mediator of COPD progress in patients with low vitamin D levels.

We report a case of a 26-year-old Chinese man who had experienced three grand mal seizures in the past two months. Magnetic resonance imaging revealed a relatively well-circumscribed lesion in the left frontal lobe. A craniotomy with total excision of the tumor was performed. Histopathological investigations confirmed a grade 2 ependymoma according to the World Health Organization classification. Genetic analysis revealed a tumor harboring FAM118B fusion to YAP1, and no other genetic alterations or methylation of the O6 -methylguanine-DNA methyltransferase gene promoter were detected. This is the second case report of ependymoma with YAP1:FAM118B fusion.

Parkinson protein 7 (PARK7)/DJ-1 (DJ-1) is a redox sensitive molecular and stabilizer of nuclear factor erythroid 2-related factor 2 (Nrf-2). Nrf-2 regulates the downstream antioxidant defense system and exerts a significant function in patients with chronic obstructive pulmonary disease (COPD). Vitamin D receptor (VDR) is the nuclear receptor that regulates the downstream target genes. This study aimed to analyze the associations among pulmonary function, DJ-1, VDR and Nrf-2 in COPD patients. Serum was collected from 180 COPD patients and control subjects. Thirty-five lung tissues were obtained. DJ-1 was measured using ELISA and western blotting. Nrf-2 and VDR were detected by immunohistochemistry. Serum and pulmonary DJ-1 levels were lower in COPD patients than those in control subjects. Pulmonary VDR-positive nuclei were reduced in COPD patients. Nrf-2-positive nuclei were reduced in lung tissues of COPD patients. On the contrary, Nrf-2-related downstream target proteins were elevated in COPD patients. Further correlation analysis indicated that forced expiratory volume in 1 second (FEV1) was positively associated with pulmonary DJ-1, VDR and Nrf-2 in patients with COPD. In addition, there were positive correlations among DJ-1, VDR and Nrf-2 in lung tissues of COPD patients. In conclusion, DJ-1, VDR and Nrf-2 were decreased in COPD patients compared with control subjects. The reduction of DJ-1 and VDR associating with Nrf-2 downregulation may be involved in the process of COPD.

Waldenstrom’s macroglobulinemia (WM) is an indolent B-cell non-Hodgkin lymphoma characterized by lymphoplasmacytic histology in the bone marrow with monoclonal IgM. Median survival can be in excess of 10 years. The 5-year cumulative incidence of death is low at about 10%. One-third of all-cause specific mortality is due to the lymphoma for which histologic transformation (HT) is rare. Here we present a case of a 60-year-old man with longstanding untreated WM, presenting with minimally symptomatic transformation to diffuse large B-cell lymphoma (DLBCL), with an accompanying review of the literature. Transformed WM, diagnosed greater than 5 years, has a reported survival period of 8 - 9 months. This case highlights that after a decade of continued stability in WM, not requiring treatment, an acute change in laboratory data with minimally progressive IgM levels, in the absence of B symptoms and clinical findings, may be the harbinger of transformation and at the time of diagnosis can have a rapidly deteriorating clinical course. In this case, the tripling of the lactate dehydrogenase (LDH) as the primary drastic change demonstrates the importance of the rapid increase in LDH as a singly reliable marker for HT. Late transformation has been borne out as a negative variable as the generally indolent course of WM is curtailed with the poor outcome in HT. Although MYD88 wildtype is a possible predictive factor for transformation, it is unclear if late transformation is clonally or non-clonally related and further molecular investigation is needed.

Multiple myeloma (MM) is a hematologic tumor with monoclonal proliferation of malignant plasma cells in the bone marrow. Fascin (FSCN) is an actin-binding protein that plays a crucial role in cell migration and invasion, contributing to tumor metastasis. There are three members (FSCN1-3) in FSCN family. However, the prognostic role of FSCN family in MM remains unclear. In this study, we used four independent Gene Expression Omnibus (GEO) datasets to explore the relationships between FSCN1-3 expression profiles and patient survival in MM. We found that FSCN1 was dramatically down-regulated in MM compared to normal donors (p < 0.001) and monoclonal gammopathy of undetermined significance (MGUS) (p = 0.032). Patients with high expression of FSCN1 and FSCN2 had significantly longer OS (p = 0.023 and 0.028, respectively). Univariate and multivariate analysis showed that FSCN1 (p = 0.003, 0.002) and FSCN2 (p = 0.018, 0.013) were independent favorable prognostic factors for OS in MM. Moreover, the combination of high expression of FSCN1 and FSCN2 could effectively predict both longer EFS (p = 0.046) and OS (p = 0.015). Our study suggested that FSCN1 and FSCN2 can be used as favorable biomarkers for predicting clinical outcomes in MM.

Background and Aims: Coronavirus disease 2019 (COVID-19) is a new respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (commonly known as SARS-CoV-2) with multiple organ injuries. The aim of this study was to analyze COVID-19-associated liver dysfunction (LD), its association with the risk of death and prognosis after discharge. Methods: Three-hundred and fifty-five COVID-19 patients were recruited. Clinical data were collected from electronic medical records. LD was evaluated and its prognosis was tracked. The association between LD and the risk of death was analyzed. Results: Of the 355 COVID-19 patients, 211 had mild disease, 88 had severe disease, and 51 had critically ill disease. On admission, 223 (62.8%) patients presented with hypoproteinemia, 151(42.5%) with cholestasis, and 101 (28.5%) with hepatocellular injury. As expected, LD was more common in critically ill patients. By multivariate logistic regression, male sex, older age and lymphopenia were three important independent risk factors predicting LD among COVID-19 patients. Risk of death analysis showed that the fatality rate was higher in patients with hypoproteinemia than in those without hypoproteinemia (relative risk=9.471, p

Introduction: The efficacy of atorvastatin for dilated cardiomyopathy remains controversial. We conducted a systematic review and meta-analysis to explore the influence of atorvastatin on cardiac performance for dilated cardiomyopathy. Methods: We searched PubMed, Embase, Web of Science, EBSCO, and Cochrane library databases through February 2019 for randomized controlled trials (RCTs) assessing the effect of atorvastatin on cardiac performance for dilated cardiomyopathy. This meta-analysis was performed using the random-effects model. Results: Five RCTs involving 401 patients were included in the meta-analysis. Overall, compared with control groups for dilated cardiomyopathy, atorvastatin treatment resulted in a significantly positive impact on left ventricular ejection fraction (standard mean difference [SMD] = 0.58; 95% confidence interval [CI] = 0.33 to 0.84; P < .00001), 6-minute walk test (SMD = 0.79; 95% CI = 0.27 to 1.31; P = .003), N-terminal pro-brain natriuretic peptide (SMD = –0.60; 95% CI = –1.18 to –0.01; P = .04), left ventricular systolic volume (SMD = 0.41; 95% CI = 0.03 to 0.79; P = .03), low-density lipoprotein (SMD = –1.37; 95% CI = –1.92 to –0.82; P = .00001), and C-reactive protein (SMD = –0.47; 95% CI = –0.72 to –0.22; P = .0002), but showed no obvious influence on left ventricular end-diastolic volume (SMD = 0.14; 95% CI = –0.37 to 0.64; P = .59). Conclusions: Atorvastatin treatment provides significant benefits for dilated cardiomyopathy.

Acute myeloid leukemia (AML) is a clonal and heterogeneous disease characterized by a myriad of genetic defects. Genetic abnormalities are powerful prognostic factors. P21-activated kinases (PAKs) are a kind of serine/threonine protein kinases, which is regulator of plenty of oncogenic signaling pathways. The clinical and prognostic value of PAKs in AML is unclear. A total of 155 AML patients with PAK expression data from The Cancer Genome Atlas database were enrolled in this study. Eighty-four patients underwent chemotherapy only, 71 also underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the chemotherapy-only group, high PAK3 and PAK7 expression were both bound up with poor EFS and OS (all P

Multiple myeloma (MM) is a plasma cell malignancy. The minichromosome maintenance (MCM) family involve in DNA replication and is vital in limiting replication in cell cycle. The prognostic role of MCMs in MM is still unclear. We took four independent GEO datasets to analyze the relationship between the expression of MCMs and myeloma progression and survival. The expression of MCMs showed an upward trend with myeloma progression in 205 patients. High MCM2/3/4/6/8 expression was associated with both poor EFS and OS (all p

The mammalian target of rapamycin (mTOR) inhibitor, DNA damage inducible transcript 4 (DDIT4), has inducible expression in response to various cellular stresses. In multiple malignancies, studies have shown that DDIT4 participates in tumorigenesis and impacts patient survival. We aimed to study the prognostic value of DDIT4 in acute myeloid leukaemia (AML), which is currently unclear. Firstly, The Cancer Genome Atlas was screened for AML patients with complete clinical characteristics and DDIT4 expression data. A total of 155 patients were included and stratified according to the treatment modality and the median DDIT4 expression levels. High DDIT4 expressers had shorter overall survival (OS) and event-free survival (EFS) than the low expressers among the chemotherapy-only group (all P

Background: Multiple myeloma (MM) is the second most common hematologic malignancy worldwide and does not have sufficient prognostic indicators. FCER1G (Fc fragment Of IgE receptor Ig) is located on chromosome 1q23.3 and is involved in the innate immunity. Early studies have shown that FCER1G participates in many immune-related pathways encompassing multiple cell types. Meanwhile, it is associated with many malignancies. However, the relationship between MM and FCER1G has not been studied.Methods: In this study, we integrated nine independent gene expression omnibus (GEO) datasets and analyzed the associations of FCER1G expression and myeloma progression, ISS stage, 1q21 amplification and survival in 2296 myeloma patients and 48 healthy donors.Results: The expression of FCER1G showed a decreasing trend with the advance of myeloma. As ISS stage and 1q21 amplification level increased, the expression of FCER1G decreased (P = 0.0012 and 0.0036, respectively). MM patients with high FCER1G expression consistently had longer EFS and OS across three large sample datasets (EFS: P = 0.0057, 0.0049, OS: P = 0.0014, 0.00065, 0.0019 and 0.0029, respectively). Meanwhile, univariate and multivariate analysis indicated that high FCER1G expression was an independent favorable prognostic factor for EFS and OS in MM patients (EFS: P = 0.006, 0.027, OS: P =0.002,0.025, respectively).Conclusions: The expression level of FCER1G negatively correlated with myeloma progression, and high FCER1G expression may be applied as a favorable biomarker in MM patients.

Background Some studies previously demonstrated that interleukin-17 (IL-17) involves in pulmonary diseases progression. Nevertheless, the role of IL-17 in community-acquired pneumonia (CAP) remains unknown. This study aims to examine the correlations between serum IL-17 with the severity and prognosis in CAP patients through a prospective cohort study. Methods All 239 CAP patients were recruited. Serum IL-17 was detected by enzyme-linked immunosorbent assay (ELISA). The CAP severity was evaluated through CAP severity scores, including CURB-65, CRB-65, PSI, SMART-COP, CURXO and APACHE II. Results Serum IL-17 was gradually increased consistent with the severity of CAP. Correlative analysis suggested that serum IL-17 was associated with clinical physiologic indicators among CAP patients. Logistic regression indicated that serum IL-17 was positively related to CAP severity scores. Additionally, the prognostic outcomes were tracked among CAP patients. The levels of IL-17 on admission were significantly increased in CAP patients with ICU admission, mechanical ventilation, vasoactive agent, death and longer hospitalization days. Logistic regression analyses revealed serum higher IL-17 on admission elevated the risks of vasoactive agent usage and longer hospital stays in CAP patients. The cut-off concentrations of serum IL-17 for death, ICU admission, mechanical ventilation and ≥ 14 hospital stays were 86.80 ng/mL, 84.92 ng/mL, 84.92 ng/mL and 60.29 ng/mL respectively. Conclusions Serum IL-17 on admission is positively associated with the severity and poor prognosis among CAP patients, revealing that IL-17 may implicate in the pathological process of CAP. Therefore, serum IL-17 may become an effective biomarker for diagnosis, prognosis and therapy for CAP patients.

Background: Cysteine-rich 61 (CYR61) and inflammation was upregulated in the lungs of patients with chronic obstructive pulmonary disease (COPD). However, the association between CYR61 and inflammation was unclear in COPD patients. This study aimed to analyze the association of serum CYR61 with pulmonary inflammation and lung function indexes in COPD patients.Methods: One hundred and fifty COPD patients and 150 control subjects were enrolled. Serum and pulmonary CYR61 was detected. Lung function indexes were evaluated in COPD patients.Results: Serum CYR61 level was elevated and pulmonary CYR61 expression was upregulated in COPD patients. An increased CYR61 was associated with decreased pulmonary function indexes in COPD patients. Further analyses showed that nuclear factor-kappa B (NF-κB) p65-positive nuclei was elevated in the lungs of COPD patients with high level of CYR61. Accordingly, serum monocyte chemotactic protein (MCP)-1 and tumor necrosis factor α (TNF-α), two downstream inflammatory cytokines of NF-κB pathway, were increased in parallel with CYR61, among which serum MCP-1 and TNF-α were the highest in COPD patients with high level of CYR61. Moreover, a positive correlation, determined by multivariate regression that excluded the influence of age, gender and smoking, was observed between serum CYR61 and inflammatory cytokines in COPD patients.Conclusion: These results provide evidence that an increased CYR61 is associated with pulmonary inflammation and COPD progression. Inflammatory cytokines may be the mediators between CYR61 elevation and COPD progression.

Aim To investigate the long-term changes of peripheral anterior synechia (PAS) after phacoemulsification with goniosynechialysis under an ophthalmic endoscope (Phaco-OE-GSL) in primary angle-closure glaucoma (PACG) assisted with viscoelastics alone or viscoelastics combined with iris repositor (viscoelastics-repositor). Method A retrospective study was conducted. Thirty-nine eyes of 31 PACG patients were included. The follow-up period was 36 months. The main outcomes of the study included the changes of PAS, intraocular pressure (IOP), and the success rate.Results Phaco-OE-GSL was performed assisted with viscoelastics-alone on 20 eyes, and viscoelastics-repositor on 19 eyes. The total recurrence rates of PAS were 62.5% in viscoelastics-alone group and 87.5% in viscoelastics-repositor group. In particular, the recurrence rate of PAS at the same location at which were separated intraoperatively were 37.3% and 75.0% respectively (P=0.033). The recurrence of PAS was observed in 2 eyes in viscoelastics-alone group and 12 eyes in viscoelastics-repositor group within 1-month follow-up (P0.05). The extent of postoperative PAS at final follow-up was positively correlated with the range of PAS preoperatively (P=0.036, r=0.356). The complete success rates were 85.0% and 89.5% of viscoelastics-alone group and viscoelastics-repositor group at 36-month follow-up respectively. Both the preoperative and postoperative distribution of PAS are mainly concentrated on the upper (84.6% and 95.8%) and nasal side (74.4% and 62.5%), followed by the inferior side, and the least on the temporal side. Conclusion In summary, although the recurrence rate of PAS was high in early postoperative period, the progression of PAS was rapidly resolved after 6 months postoperatively, and Phaco-OE-GSL is an effective treatment for the long-term control of IOP of PACG patients especially with large range of PAS (> 180°). Both preoperative and postoperative PAS are mainly concentrated on the upper and nasal side. Besides, our results suggested that mechanical separation may be easier to promote the progression of postoperative PAS than viscoelastics-alone separation.

Introduction Mild encephalopathy with a reversible splenial lesion (MERS) is a clinical-radiologic syndrome presenting with a reversible lesion in the splenium of the corpus callosum. MERS is associated with many potential etiologies, including cytomegalovirus (CMV) infection in children. We report an adult patient with CMV-associated MERS. Case report A previously healthy 25-year-old man was admitted with a 4-day history of fever, headache, and vomiting. Brain magnetic resonance imaging demonstrated an isolated lesion of the splenium of the corpus callosum with hyperintensity on T2 and diffusion-weighted sequences and reduced values on apparent diffusion coefficient maps. High throughput gene detection for pathogens in cerebrospinal fluid revealed infection with CMV. The splenial lesion resolved 4 weeks after onset. Conclusion This is the first report an adult patient with CMV-associated MERS. Recognition of this clinical-radiologic syndrome can guide diagnosis and management.

BACKGROUND Cadmium is a ubiquitous toxic heavy metal and environmental toxicant. Inflammation exerts central roles in the process of chronic obstructive pulmonary disease (COPD). However, few epidemiological studies on the correlation between cadmium exposure and COPD are available. The aim of this study was to evaluate the correlations among serum cadmium, inflammatory cytokines and pulmonary function in COPD patients. METHODS All 940 COPD patients were finally recruited in this study. Demographic characteristics and clinical information were extracted. Fasting serum was collected. Serum cadmium was detected through graphite furnace atomic absorption spectrophotometry. Serum inflammatory cytokines were measured using enzyme-linked immunosorbent assay. RESULTS All patients were classified into three groups according to the tertile division of serum cadmium concentration: low (

Purpose To measure the changes of macular microcirculation in cases with unilateral acute primary angle closure (APAC) who were managed by phacoemulsification. Methods Patients with unilateral APAC and managed by phacoemulsification were enrolled. The contralateral unaffected eyes were served as fellow group, and normal individuals were recruited as control group. Optical coherence tomography angiography (OCT-A) was performed to analyse the macular whole image vessel density (wiVD) and parafoveal vessel density (pfVD). The retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thicknesses were assessed using spectral-domain optical coherence tomography. Results A total of 36 APAC patients and 35 eyes from 35 normal individuals were recruited. In the APAC eyes, the mean wiVD (42.1% ± 3.7%) and pfVD (45.2% ± 3.8%) in the superficial layers (wiVD-SL and pfVD-SL) were both significantly reduced, compared to fellow eyes (45.7% ± 3.1%, 48.7% ±3.1%) and control eyes (44.4% ± 4.7%, 47.4% ± 5.1%) (P

BackgroundPrevious studies indicated the calcium-binding protein S100A12 to be involved in the pathophysiology of pulmonary inflammatory diseases. However, the role of S100A12 has remained elusive in patients with community-acquired pneumonia (CAP). Therefore, the purpose of this prospective cohort study was to evaluate the association between serum S100A12 with severity and prognosis in CAP patients.MethodsTwo groups with either 239 CAP patients or 239 healthy controls were enrolled in our study. Fasting blood and clinical characteristics were collected. On admission, serum S100A12 was measured using enzyme-linked immunosorbent assay (ELISA).ResultsSerum S100A12 was increased in CAP patients compared to control subjects. Furthermore, serum S100A12 was elevated according to the severity of CAP. Correlative analysis suggested that the level of serum S100A12 was associated with blood routine indices, renal function markers, inflammatory cytokines and other clinical parameters among CAP patients. Additionally, linear and logistical regression analyses indicated that serum S100A12 was positively associated with CAP severity scores in CAP patients. In addition, the association of high serum S100A12 and prognosis was accessed using a follow-up research. Elevated serum S100A12 on admission increased the risk of death and hospital stay in CAP patients during hospitalization.ConclusionsElevated serum S100A12 on admission is positively associated with the severity and adverse prognosis in CAP patients, suggesting that S100A12 may involve in the pathophysiological process of CAP. The titre of serum S100A12 may be used as a biomarker for diagnosis and prognosis among CAP patients.

BackgroundResistin is an endogenous ligand of Toll-like receptor 4 that activates several inflammatory signals. But the physiological function of resistin in community-acquired pneumonia (CAP) remains unknown. The goal of this research was to explore the associations between serum resistin and the severity and prognosis in CAP patients through a retrospective cohort study.MethodsAll 212 CAP patients and 106 healthy cases were enrolled. Demographic characteristics were extracted. Serum resistin was determined via enzyme-linked immunosorbent assay. The prognosis was tracked in CAP patients.ResultsSerum resistin on admission was raised in CAP patients compared with control cases. The level of resistin was gradually increased in parallel with CAP severity scores in CAP patients. Pearson and Spearman analyses revealed that serum resistin was positively correlated with CAP severity scores, white blood cells, urea nitrogen, creatinine, and inflammatory cytokines among CAP patients. There were negative relationships between resistin and hematocrit and albumin in CAP patients. Besides, linear and logistic regression analyses further indicated that serum resistin on admission was positively associated with CAP severity scores among CAP patients. Follow-up research revealed that serum resistin elevation on admission prolonged hospital stay in CAP patients.ConclusionSerum resistin on admission is positively correlated with the severity and hospital stay in CAP patients, indicating that resistin may be involved in the physiological process of CAP. Serum resistin may be a potential biomarker in the diagnosis and prognosis for CAP.

iASPP is a negative regulator of the apoptotic function of p53, and it can enhance the ability of hematopoietic stem cells to self-renew and resist chemo- and radiation therapy. Recent study showed that iASPP could impact the proliferation and apoptosis of leukemia cells by interacting with FHL2. However, whether they have prognostic significance in acute myeloid leukemia (AML) is unknown. Eighty-four AML patients with FHL2 and iASPP expression data from The Cancer Genome Atlas database were enrolled in the study. Patients with high expressions of FHL2 and iASPP had significantly shorter event-free survival (EFS) and overall survival (OS) than patients with low expressions (P = 0.005, P = 0.003, respectively). Univariate analysis indicated that high expressions of FHL2 or iASPP were unfavorable for EFS and OS (all P

Several epidemiological reports demonstrated that vitamin D deficiency elevated risk of preterm delivery. We investigate the effects of oral cholecalciferol (VD3) supplementation on lipopolysaccharide (LPS)-induced preterm delivery. Pregnant mice were randomly assigned to either oral VD3 (25 μg/kg) or corn oil once daily from gestational day (GD)13 to GD15, and were intraperitoneally injected with either LPS (200 μg/kg) or normal saline on GD15. As expected, LPS was effective in inducing preterm delivery and fetal death. LPS-induced preterm delivery and fetal death were alleviated in VD3-pretreated mice. LPS-induced down-regulation of genes for placental progesterone biosynthetic enzymes was blocked in VD3-pretreated mice. LPS-induced reduction of serum progesterone was correspondingly attenuated by VD3. Although oral VD3 had no effect on estradiol production, it attenuated LPS-induced up-regulation of placental ERβ in mice. LPS-induced placental COX-2 up-regulation and serum PGF2α elevation were alleviated in VD3-pretreated mice. Additionally, LPS-evoked elevations of the placental Tnfα, Il1β, Mcp1 and Mip2 mRNAs were attenuated by VD3. VD3 promoted placental vitamin D receptor nuclear translocation and simultaneously alleviated LPS-induced nuclear translocation of NF-κB p65 and p50 subunits. These results provide evidence that oral VD3 supplementation alleviates LPS-induced preterm delivery and fetal demise partially through regulating placental steroid hormones and prostaglandins.

Gaoqi Zhang,1 Jilei Zhang,2 Xinrui Yang,1 Xinpei Zhang,1 Siyuan Yang,1 Jing Wang,1 Kai Hu,1 Jinlong Shi,3,4 Xiaoyan Ke,1 Lin Fu11Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, People’s Republic of China; 2Department of Otolaryngology, Peking University People’s Hospital, Beijing 100044, People’s Republic of China; 3Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China; 4Department of Medical Big Data, Chinese PLA General Hospital, Beijing 100853, People’s Republic of ChinaBackground: Overexpression of dedicator of cytokinesis 1 (DOCK1) has been confirmed as an unfavorable prognostic marker in acute myeloid leukemia (AML). Purpose: This study is to explore the clinical implications of DOCK1 on AML patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients and methods: We analyzed 71 de novo AML patients treated with allo-HSCT and divided them into two groups (DOCK1high, vs DOCK1low,) by the median expression level of DOCK1. Results: High DOCK1 expression was associated with older age (P=0.019), wild-type CEBPA (P=0.002), IDH1/2 mutations (P=0.010) and RUNX1 mutation (P=0.005). Univariate analyses showed that DOCK1high, and RUNX1 mutation were associated with shorter OS (P

Acute myeloid leukemia (AML) is a malignancy caused by the uncontrolled and dysregulated clonal expansion of abnormal myeloid primordial cells. In general, the prognosis of AML remains poor despite new discoveries in its pathogenesis and treatment. It is crucial to find early and sensitive biomarkers and continue to explore active targeted treatments. Interferon-induced transmembrane protein (IFITM) family is an important part of the interferon signaling pathway and participate in the regulation of immune cell signaling, adhesion, cancer, and liver cell migration. However, the clinical and prognostic value of the IFITM family in AML has rarely been studied. We screened The Cancer Genome Atlas database and found 155 AML patients with IFITM family (IFITM1-5) expression data. In patients who only received chemotherapy, those with high IFITM3 expression had significantly shorter event-free survival (EFS) and overall survival (OS) than patients with low expression (all P

The aim of the present study was designed to investigate that Platycodon grandiflorum saponins (PGS) exerted protective effects against testicular injury induced by scrotal hyperthermia. PGS (15, 30 mg/kg) were administered intragastrically to mice for 14 days, then exposed to a single scrotal heat treatment at 43 °C for 18 min on the 7th day. Heat stress (HS) induced spermatogenic damage was associated with a significant loss of leydig cells and the changes of serum testosterone, oxidative stress and apoptosis markers, and activated MAPK signaling pathway. In contrast, PGS treatment normalized HS-induced histopathological changes and prevented the activation of MAPK signaling pathway, which was contributed to oxidative stress and apoptosis in the testis of treated mice. In conclusion, our findings clearly demonstrated that PGS exhibited a significant protective effect against HS-induced testicular dysfunction, largely dependent upon the inhibition of oxidative stress associated apoptosis via partly regulation of MAPK signaling pathway.

Background To investigate the occurrence of ciliochoroidal detachment (CCD), its risk factors and its impact on the success rate after Ahmed glaucoma valve (AGV) implantation. Methods This is a retrospective observational study carried out at Eye Hospital of Wenzhou Medical University, Zhejiang, China. Patients with uncontrolled glaucoma who underwent AGV implantation alone or combined with phacoemulsification (AGV-Phaco) in the hospital from April 1, 2013 to July 31, 2016 were included. The preoperative and postoperative CCD was defined when the detachment between ciliary body and choroid was detected by the ultrasound biomicroscopy (UBM) and anterior segment optical coherence tomography (AS-OCT) respectively. The main outcomes included the incidence of CCD and the success rate at 6 months after surgery. Results In total, 97 male and 56 female patients were included. CCD was observed in 92 (57.8%) eyes. The glaucoma diagnosis in the Non-CCD and CCD group included primary open angle glaucoma (21(31.3%) vs 33(35.9%)), primary angle closure glaucoma (10(14.9%) vs 13(14.1%)), secondary glaucoma (25(37.3%) vs (28(30.4%)) and so on. The preoperative median IOP (interquartile range) were 21.7(16.0,32.0) mmHg and 23.0(16.0,33.0) mmHg in the Non-CCD group and CCD group. Previous surgical history (95% confidence interval (CI), 1.24 to 13.34; odds ratio (OR) 4.06; p = 0.02) and shorter axial length (95% CI, 0.62 to 0.97 OR 0.78; p = 0.02) were the two risk factors of CCD. The success rate between the CCD and Non-CCD group was not significantly different (64.3% vs 62.5%, p = 0.86) at 6 months. Conclusions The incidence of CCD is 57.8% after AGV surgery. Eyes with previous surgical procedure was prone to CCD occurrence and longer axial length was protective against CCD. But at 6 months postoperatively, CCD did not reduce the success rate of AGV surgery and may not be a worrisome complication.

It has been demonstrated that microRNA-98 (miR-98) is dysregulated in multiple types of solid tumors, but its expression and impact in acute myeloid leukemia (AML) is unclear. To explore the prognostic role of miR-98 in AML, 164 AML patients with the miR-98 expression data were extracted from The Cancer Genome Atlas (TCGA) database and enrolled in this study. First, patients were divided into chemotherapy-only (chemotherapy) group and allogeneic hematopoietic stem cell transplant (allo-HSCT) group. Each group was then divided in two groups by the median expression level of miR-98. In chemotherapy group, high miR-98 expression was associated with longer event-free survival (EFS, P = 0.003) and overall survival (OS, P = 0.004), but in allo-HSCT group, EFS and OS were not significantly different between high and low miR-98 expressers. Second, All patients were divided in two groups by the median expression level of miR-98. In low miR-98 expressers, those treated with allo-HSCT had longer EFS (P = 0.001) and OS (P < 0.001) than chemotherapy, but in high miR-98 expressers, survival was independent from treatment modalities. Gene ontology enrichment analysis indicated that the genes associated with miR-98 expression were mainly concentrated in "definitive hemopoiesis", "negative regulation of myeloid cell differentiation" and "signaling pathways regulating pluripotency of stem cells" pathways. In conclusion, our results indicated that high miR-98 expression confers good prognosis in AML patients treated with chemotherapy alone. Patients with low miR-98 expression may benefit from allo-HSCT.

The prognostic value of tumor characteristics for glioma has been controversial, partly because of a lack of knowledge about how these associations develop. Extent of resection may be factors that mediate the relationship between tumor characteristics and the hazard of death from glioma. Patients and Methods: This consecutive study retrospectively included a group of 393 treatment-naive patients with newly, pathologically confirmed glioma between January 2004 and December 2014. Information on patient age, gender, Karnofsky Performance Status (KPS), tumor grade, tumor size, tumor location, presence or absence of contrast enhancement on MRI and extent of tumor resection have all been collected. The discrete-time survival model integrating survival outcomes within structural equation models was employed to develop and evaluate a comprehensive hypothesis regarding the direct and indirect impact of tumor characteristics on the hazard of death from glioma, mediated by the extent of resection. Results: Except for tumor location, the indirect effects of tumor grade, contrast enhancement, and tumor size on PFS of glioma through extent of resection were found significant in the model. Conclusion: This study provides a better understanding of the process through which tumor characteristics is associated with hazard of death from glioma.

DOCK family proteins are evolutionarily conserved guanine nucleotide exchange factors for Rho GTPase with different cellular functions. It has been demonstrated that DOCK1 had adverse prognostic effect in acute myeloid leukemia (AML). We first analyzed data of 85 AML patients who were treated with chemotherapy and had available DOCK1 to DOCK11 expression information and found that DOCK1 and DOCK2 had prognostic significance in AML. In view of the known prognosis of DOCK1 in AML, we then explored the prognostic role of DOCK2. One hundred fifty-six AML patients with DOCK2 expression data were extracted from The Cancer Genome Atlas (TCGA) database and enrolled in this study. Patients were divided based on treatment modality into the chemotherapy group and the allogeneic hematopoietic stem cell transplant (allo-HSCT) group. Each group was divided into two groups by the median expression levels of DOCK2. In the chemotherapy group, high DOCK2 expression was associated with longer event-free survival (EFS, P=0.001) and overall survival (OS, P=0.007). In the allo-HSCT group, EFS and OS were not significantly different between high and low DOCK2 expression groups. Multivariate analysis showed that high DOCK2 expression was an independent favorable prognostic factor for both EFS and OS in all patients (all P

Background: Actinins are major cytoskeletal proteins that mediate sarcomere function, and they also have important non-muscle functions such as regulating cytokinesis, cell adhesion and migration. There are four isoforms of actinins in mammals (ACTN1-4). Recently, the relationship between actinins and cancer has been discovered in many types of malignancy, yet their prognostic significance in acute myeloid leukemia (AML) remains unclear. Methods: We collected data of 155 de novo AML patients from The Cancer Genome Atlas (TCGA) database; 85 patients received chemotherapy only and 70 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We divided each treatment groups into sub-groups based on the median expression levels of ACTN1-4. Results: Survival analysis showed that in the chemotherapy-only group, high ACTN1 and ACTN3 expression were associated with shorter event-free survival (EFS) and overall survival (OS) (p

Evidence from outside the typical clinical research setting, such as the real-world setting, complements evidence coming from randomized controlled trials. The purpose of this study was to evaluate all available evidence from the real-world observational trials about long-term outcomes of treatment with intravenous (IV) recombinant tissue-type plasminogen activator (rt-PA) compared with not treated with IV rt-PA (non-rt-PA) in patients with acute ischemic stroke.We searched PubMed and Embase until March 1, 2018 for observational studies reporting matched or adjusted results comparing IV rt-PA versus non-rt-PA in patients with acute ischemic stroke. Outcomes assessed included all-cause mortality, hospital readmission rates, and independence rates. Hazard ratios with 95% confidence intervals were used as a measure of comparing between patients treated with IV rt-PA and non-rt-PA.Six observational trials with 16,399 participants were identified. The use of IV rt-PA in acute ischemic stroke patients was associated with a lower risk of mortality (hazard ratio .61; 95% confidence interval, .52-.70; P.00001), and there was no heterogeneity across trials. There was no evidence of an effect on hospital readmission rates and independence rates.IV rt-PA is associated with reduced long-term mortality in acute ischemic stroke patients.

Background The receptor tyrosine kinase FLT3 with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) is a poor prognostic factor; however, the prognostic significance of missense mutation in the tyrosine kinase domain (FLT3-TKD) is controversial. Furthermore, the accompanying mutations and fusion genes with FLT3 mutations are unclear in acute myeloid leukemia (AML). Methods We investigated FLT3 mutations and their correlation with other gene mutations and gene fusions through two RNA-seq based next-generation sequencing (NGS) method and prognostic impact in 207 de novo AML patients. Results FLT3-ITD mutations were positive in 58 patients (28%), and FLT3-TKD mutations were positive in 20 patients (9.7%). FLT3-ITD was associated with a higher white blood cell count (WBC, mean 72.9 × 109/L vs. 24.2 × 109/L, P = 0.000), higher bone marrow blasts (mean 65.9% vs. 56.0%, P = 0.024), and NK-AML (normal karyotype) (64.8% vs. 48.4%, P = 0.043). NPM1 and DNMT3A mutations were enriched in FLT3-ITD (53.5% vs. 15.3%, P = 0.000; 34.6% vs. 13%, P = 0.003). However, the mutations of CEBPA were excluded in FLT3-AML (3.8% vs. 0% vs. 19.8%, P = 0.005). Mutations of Ras and TP53 were unlikely associated with FLT3-ITD (1.9% vs. 20.6%, P = 0.006; 0% vs. 6.1%, P = 0.04). The common fusion genes (> 10%) in FLT3-ITD had MLL-rearrangement and NUP98-rearrangement, while the common fusion genes in FLT3-TKD had AML1-ETO and MLL-rearrangement. Two novel fusion genes PRDM16-SKI and EFAN2-ZNF238 were identified in FLT3-ITD patients. Gene fusions and NPM1 mutation were mutually excluded in FLT3-ITD and FLT3-TKD patients. Their patterns of mutual exclusivity and cooperation among mutated genes suggest that additional driver genetic alterations are required and reveal two evolutionary patterns of FLT3 pathogenesis. Patients with FLT3-ITD had a lower CR (complete remission) rate, lower 3-year OS (overall survival), DFS (disease-free survival), and EFS (event-free survival) compared to FLT3wtAML. NK-AML with FLT3-ITD had a lower 3-year OS, DFS, and EFS than those without, while FLT3-TKD did not influence the survival in whole cohort and NK-AML. Besides, we found that FLT3-ITD/TET2 bimutation defined a poor prognostic subgroup. Conclusions Our study offers deep insights into the molecular pathogenesis and biology of AML with FLT3-ITD and FLT3-TKD by providing the profiles of concurrent molecular alterations and the clinical impact of FLT3-ITD and FLT3-TKD on AML patients.

Background Previous studies found that S100A9 may involve in the pathophysiology of community-acquired pneumonia (CAP). However, the role of S100A9 was unclear in the CAP. The goal was to explore the correlations of serum S100A9 with the severity and prognosis of CAP patients based on a prospective cohort study. Methods A total of 220 CAP patients and 110 control subjects were recruited. Demographic and clinical data were collected. Serum S100A9 and inflammatory cytokines were measured. Results Serum S100A9 was elevated in CAP patients on admission. Serum S100A9 was gradually elevated parallelly with CAP severity scores. Additionally, inflammatory cytokines were increased and blood routine parameters were changed in CAP patients compared with control subjects. Correlation analysis found that serum S100A9 was positively associated with CAP severity scores, blood routine parameters (WBC, NLR and MON) and inflammatory cytokines. Further, logistic regression analysis demonstrated that there were positive associations between serum S100A9 and CAP severity scores. Besides, the prognosis of CAP was tracked. Serum higher S100A9 on the early stage elevated the death of risk and hospital stay among CAP patients. Conclusion Serum S100A9 is positively correlated with the severity of CAP. On admission, serum higher S100A9 elevates the risk of death and hospital stay in CAP patients, suggesting that S100A9 may exert a certain role in the pathophysiology of CAP and regard as a serum diagnostic and managing biomarker for CAP.

Acute myeloid leukemia (AML) is a heterogeneous blood disease with poor treatment effect and high recurrence rate. With the deepening of non-coding RNA research, more and more miRNAs have been found to participate in various physiological processes of tumors. In this study, we tried to find the miRNA related to the prognosis of AML. Collect gene expression data and clinical information of AML patients in the Cancer Genome Atlas database for statistical analysis. The expression level of miR-195 of each patient was standardized by logCPM and then produced as a box plot according to subtype classification. TargetScan was used to predict the target genes of miR-195, and these genes were subjected to GO pathway enrichment analysis by Metascape. Differential miRNAs were screened through the DESeq2 package in the R language. Survival rates were estimated using the Kaplan–Meier method and the log-rank test. The multivariate Cox proportional hazard models of EFS and OS were established. We found that the expression of miR-195 was the lowest in cytogenetically normal (CN-) AML, and high expression of miR-195 only promoted the prognosis of chemotherapy-only CN-AML patients (EFS: P = 0.016; OS: P = 0.035). Multivariate analysis showed that miR-195high was a favorable and independent factor for CN-AML (both P

Stroke rehabilitation focuses on alleviating post-stroke disability. Post-acute care (PAC) offers an intensive rehabilitative program as transitional care following acute stroke. A novel home-based PAC program has been initiated in Taiwan since 2019. Our study aimed to compare the current inpatient PAC model with a novel home-based PAC model in cost-effectiveness and functional recovery for stroke patients in Taiwan. One hundred ninety-seven stroke patients eligible for the PAC program were divided into two different health interventional groups. One received rehabilitation during hospitalization, and the other received rehabilitation by therapists at home. To evaluate the health economics, we assessed the total medical expenditure on rehabilitation using the health system of Taiwan national health insurance and performed cost-effectiveness analyses using improvements of daily activity in stroke patients based on the Barthel index (BI). Total rehabilitative duration and functional recovery were also documented. The total rehabilitative cost was cheaper in the home-based PAC group (p &lt, 0.001), and the cost-effectiveness is USD 152.474 ± USD 164.661 in the inpatient group, and USD 48.184 ± USD 35.018 in the home group (p &lt, 0.001). Lesser rehabilitative hours per 1-point increase of BI score was noted in the home-PAC group with similar improvements in daily activities, life quality and nutrition in both groups. Home-based PAC is more cost-effective than inpatient PAC for stroke rehabilitation.

BACKGROUND: CPNEs are significant biomarkers which can affect the progression and prognosis of various tumor diseases. However, the prognosis role of CPNEs in multiple myeloma (MM) is still unclear. OBJECTIVES: To investigate the prognosis role of CPNEs in MM. METHODS: Seven hundred and thirty-five samples from two independent data sets were involved to analyze the clinical and molecular characteristics, and prognosis role of the expression of CPNE1-9 in MM. RESULTS: MM patients with higher expressions of CPNE5 and CPNE9 had longer event-free survival (EFS) and overall survival (OS) compared with CPNE5low and CPNE9low expression groups (EFS: P= 0.0054, 0.0065; OS: P= 0.015, 0.016, respectively). Multivariate regression analysis showed that CPNE5 was an independent favorable predictor for EFS and OS (EFS: P= 0.005; OS: P= 0.006), and CPNE9 was an independent positive indicator for EFS (P= 0.002). Moreover, the survival probability and the cumulative event of EFS and OS in CPNE5highCPNE9high group were significantly longer than other groups. CONCLUSIONS: High expressions of CPNE5 and CPNE9 might be used as positive indicators for MM, and their combination was a better predictor for the survival of MM patients.

Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the malignant clonal expansion of lymphoid hematopoietic precursors. It is regulated by various signaling molecules such as cytokines and adhesion molecules in its microenvironment. Chemokines are chemotactic cytokines that regulate migration, positioning and interactions of cells. Many chemokine axes such as CXCL12/CXCR4 and CCL25/CCR9 have been proved to play important roles in leukemia microenvironment and further affect ALL outcomes. In this review, we summarize the chemokines that are involved in ALL progression and elaborate on their roles and mechanisms in leukemia cell proliferation, infiltration, drug resistance and disease relapse. We also discuss the potential of targeting chemokine axes for ALL treatments, since many related inhibitors have shown promising efficacy in preclinical trials, and some of them have entered clinical trials.

Background: Many studies have identified the important role of 8-isoprostane (8-iso-PGF2α) in pulmonary diseases. However, the role of 8-iso-PGF2α in community-acquired pneumonia (CAP) remains unclear. Therefore, the main goal was to investigate the correlations of serum 8-iso-PGF2α with the severity and prognosis in CAP patients through a hospital-based retrospective cohort study.Methods: All 220 patients with CAP were enrolled. Demographic information and clinical data were collected. Levels of 8-iso-PGF2α and inflammatory cytokines were detected in serum using ELISA.Results: The levels of 8-iso-PGF2α were gradually increased in parallel with the CAP severity scores. Univariate and multivariate logistic regression analyses revealed a positive association between serum 8-iso-PGF2α and the CAP severity scores. Additionally, serum 8-iso-PGF2α levels were positively correlated with circulating inflammatory cytokines (CRP and TNFα). Serum 8-iso-PGF2α levels were increased in the patients with a longer hospital stay than those with a shorter hospital stay. Additionally, 20 patients died after hospitalization. Dead patients presented a higher serum 8-iso-PGF2α than surviving patients. A subsequent survival analysis revealed that higher serum 8-iso-PGF2α levels positively correlated with the risk of death in patients with CAP.Conclusions: Serum 8-iso-PGF2α levels on admission are positively associated with the severity of CAP patients. Elevated serum 8-iso-PGF2α on admission prolongs hospital stay and increases the risk of death in patients with CAP, indicating that 8-iso-PGF2α may be involved in the progression of CAP and serve as an early serum prognostic biomarker for CAP.

BackgroundRecent evidences suggested that IL-37 may participate in the pathophysiology of community-acquired pneumonia (CAP). Nevertheless, its exact biological role was unknown. The objective of this study was to determine the associations of serum IL-37 with the severity and prognosis in CAP patients based on a retrospective cohort study.MethodsThe whole of 120 healthy subjects and 240 CAP patients were summoned. Peripheral blood was collected and IL-37 was detected using ELISA.ResultsSerum IL-37 was obviously decreased in CAP patients on admission. In addition, serum IL-37 was gradually decreased in parallel with CAP severity scores. Correlative analysis revealed that serum IL-37 was negatively associated with CAP severity scores and inflammatory cytokines. Further logistical regression found that reduction of serum IL-37 augmented the severity of CAP patients. Moreover, the follow-up research was performed in CAP patients. Serum lower IL-37 on admission prolonged the hospital stay in CAP patients. Serum IL-37 combination with PSI and CURB-65 had a stronger predictive capacity for death than IL-37 and CAP severity score alone in CAP patients.ConclusionThere are remarkably negative correlations between serum IL-37 with the severity and prognosis in CAP patients. Serum IL-37 on admission prolongs the hospital stay, demonstrating that IL-37 may involve in the process of CAP. Serum IL-37 may be regarded as a biomarker for diagnosis and prognosis for CAP patients.

Acute myeloid leukemia (AML) is a highly heterogeneous disease that requires fine-grained risk stratification for the best prognosis of patients. As a class of small non-coding RNAs with important biological functions, microRNAs play a crucial role in the pathogenesis of AML. To assess the prognostic impact of miR-20b on AML in the presence of other clinical and molecular factors, we screened 90 AML patients receiving chemotherapy only and 74 also undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. In the chemotherapy-only group, high miR-20b expression subgroup had shorter event-free survival (EFS) and overall survival (OS, both P < 0.001); whereas, there were no significant differences in EFS and OS between high and low expression subgroups in the allo-HSCT group. Then we divided all patients into high and low expression groups based on median miR-20b expression level. In the high expression group, patients treated with allo-HSCT had longer EFS and OS than those with chemotherapy alone (both P < 0.01); however, there were no significant differences in EFS and OS between different treatment subgroups in the low expression group. Further analysis showed that miR-20b was negatively correlated with genes in “ribosome,” “myeloid leukocyte mediated immunity,” and “DNA replication” signaling pathways. ORAI2, the gene with the strongest correlation with miR-20b, also had significant prognostic value in patients undergoing chemotherapy but not in the allo-HSCT group. In conclusion, our findings suggest that high miR-20b expression is a poor prognostic indicator for AML, but allo-HSCT may override its prognostic impact.

Aim: The objective of this work was to investigate the prognostic role of the HMGN family in acute myeloid leukemia (AML). Methods: A total of 155 AML patients with HMGN1–5 expression data from the Cancer Genome Atlas database were enrolled in this study. Results: In the chemotherapy-only group, patients with high HMGN2 expression had significantly longer event-free survival (EFS) and overall survival (OS) than those with low expression (all p

Primary plasma cell leukemia (PCL) is a rare and aggressive variant of multiple myeloma (MM). PCL is characterized by peripheral blood involvement by malignant plasma cells and an aggressive clinical course leading to poor survival. There is considerable overlap between MM and PCL with respect to clinical, immunophenotypic, and cytogenetic features, but circulating plasma cell count exceeding 20% of peripheral blood leukocytes or an absolute plasma cell count of >2000/mm3 distinguishes it from MM. After initial stabilization and diagnosis confirmation, treatment of PCL in a fit patient typically includes induction combination chemotherapy containing novel agents typically, with proteasome inhibitors (such as bortezomib) and immunomodulatory drugs (eg, lenalidomide), followed by autologous hematopoietic stem cell transplant (HSCT) and multidrug maintenance therapy using novel agents post-HSCT. Long-term outcomes have improved employing this strategy but the prognosis for non-HSCT candidates remains poor and new approaches are needed for such PCL patients not eligible for HSCT. Here, we report a case of primary PCL, and a comprehensive and up to date review of the literature for diagnosis and management of PCL. We also present the findings of Positron Emission Tomography (PET) scan. Since PCL is often associated with extra-medulary disease, including PET scan at the time of staging and restaging may be a novel approach particularly to evaluate the extra-medullary disease sites.

IntroductionLimited studies have suggested that calprotectin may take part in the pathophysiology of community-acquired pneumonia (CAP). Nevertheless, there is no clinical study analysing the role of S100A8 in CAP patients. The objective of this study was to analyse the association of serum S100A8 with the severity of CAP and determine the cut-off values of S100A8 for predictive power based on a cross-sectional study.Material and methodsA total of 200 CAP patients and 100 normal subjects were recruited. Demographic data, clinical information, and serum were collected on admission. S100A8 and inflammatory cytokines were detected using ELISA and RT-PCR. All statistical analyses were performed with SPSS 19.0.ResultsSerum S100A8 was increased in CAP patients on admission. Serum S100A8 was gradually increased in parallel with CAP severity scores. Serum S100A8 was positively correlated with CAP severity scores, blood routine parameters, and inflammatory cytokines. Furthermore, univariate and multivariate logistical regression revealed that there were positive associations between serum S100A8 with CRB-65, PSI, and CURXO. Moreover, the predictive capacity of serum S100A8 was determined by ROC curve analysis. The area under the curves of S100A8 for CAP and CAP severity were 0.855 and 0.893, respectively. Mechanistic analysis found that S100A8 knockdown alleviated streptococcus pneumoniae-evoked inflammatory cytokines in A549 cells.ConclusionsSerum S100A8 on admission was positively associated with the severity of CAP. S100A8 knockdown alleviates streptococcus pneumoniae-evoked inflammatory cytokines in A549 cells, indicating that S100A8 may exert a significant effect on the pathophysiology of CAP and could be an early serum diagnostic biomarker for CAP.

ObjectiveThe etiology and epidemiology of co-infection and secondary infection in COVID-19 patients remain unknown. The study aims to investigate the occurrence and characteristics of co-infection and secondary infection in COVID-19 patients, mainly focusing on Streptococcus pneumoniae co-infections.MethodsThis study was a prospective, observational cohort study of the inpatients diagnosed with COVID-19 in two designated hospitals in south China enrolled between Jan 11 and Feb 22, 2020. The urine specimen was collected on admission and applied for pneumococcal urinary antigen tests (PUATs). Demographic, clinical and microbiological data of patients were recorded simultaneously.ResultA total of 146 patients with a confirm diagnosis of COVID-19 at the median age of 50.0 years (IQR 36.0-61.0) were enrolled, in which, 16 (11.0%) were classified as severe cases and 130 (89.0%) as non-severe cases. Of the enrolled patients, only 3 (2.1%) were considered to present the co-infection, in which 1 was co-infected with S.pneumoniae, 1 with B. Ovatus infection and the other one with Influenza A virus infection. Secondary infection occurred in 16 patients, with S. maltophilia as the most commonly isolated pathogen (43.8%), followed by P. aeruginosa (25.0%), E. aerogenes (25.0%), C. parapsilosis (25.0%) and A. fumigates (18.8%).ConclusionPatients with confirmed COVID-19 were rarely co-infected with Streptococcus pneumoniae or other pathogens, indicating that the application of antibiotics against CAP on admission may not be necessary in the treatment of COVID-19 cases.

Introduction Increasing evidence indicate that coronavirus disease 2019 (COVID-19) is companied by renal dysfunction. However, the association of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced renal dysfunction with prognosis remains obscure. Materials and methods All 154 patients with COVID-19 were recruited from the Second People’s Hospital of Fuyang City in Anhui, China. Demographic characteristics and laboratory data were extracted. Renal dysfunction was evaluated and its prognosis was followed up based on a retrospective cohort study. Results There were 125 (81.2%) mild and 29 (18.8%) severe cases in 154 COVID-19 patients. On admission, 16 (10.4%) subjects were accompanied with renal dysfunction. Serum creatinine and cystatin C were increased and estimated glomerular filtration rate (eGFR) was decreased in severe patients compared with those in mild patients. Renal dysfunction was more prevalent in severe patients. Using multivariate logistic regression, we found that male gender, older age and hypertension were three importantly independent risk factors for renal dysfunction in COVID-19 patients. Follow-up study found that at least one renal function marker of 3.33% patients remained abnormal in 2 weeks after discharge. Conclusion Male elderly COVID-19 patients with hypertension elevates the risk of renal dysfunction. SARS-CoV-2-induced renal dysfunction are not fully recovered in 2 weeks after discharge.