Search

Background. MicroRNA-423 (miR-423) rs6505162 polymorphism is found to be associated with breast cancer (BC) risk. However, the results were inconsistent. This study meta-analyzed the literature on possible association between rs6505162 polymorphism and BC risk. Methods. PubMed, Embase, Google Scholar, and the Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies. Meta-analyses were performed to examine the association between rs6505162 polymorphism and BC. Results. None of the five genetic models suggested a significant association between rs6505162 polymorphism and BC risk: allelic model, OR 1.02, 95% CI 0.18–1.28, P = 0.85 ; recessive model, OR 0.99, 95% CI 0.72–1.38, P = 0.97 ; dominant model, OR 0.93, 95% CI 0.72–1.21, P = 0.60 ; homozygous model, OR 1.04, 95% CI 0.66–1.65, P = 0.87 ; and heterozygous model, OR 1.07, 95% CI 0.90–1.28, P = 0.45 . Similar results were obtained in subgroup analyses of Asian, Chinese, and Caucasian patients. Conclusion. The available evidence suggests no significant association between rs6505162 polymorphism and BC risk. These conclusions should be verified in large, well-designed studies.

Emergency granulopoiesis, also known as demand-adapted granulopoiesis, is defined as the response of an organism to systemic bacterial infections, and it results in neutrophil mobilization from reservoir pools and increased myelopoiesis in the bone marrow. Indirect and direct initiating mechanisms of emergency granulopoiesis have been hypothesized. However, the detailed mechanism of hyperactive myelopoiesis in the bone marrow, which leads to granulocyte left shift, remains unknown. In this study, we report that TLR4 is expressed on granulo-monocytic progenitors, as well as mobilized human peripheral blood CD34+ cells, which account for 0.2% of monocytes in peripheral blood, and ∼ 10% in bone marrow. LPS, a component of Gram-negative bacteria that results in a systemic bacterial infection, induces the differentiation of peripheral blood CD34+ cells into myelocytes and monocytes in vitro via the TLR4 signaling pathway. Moreover, CD34+ cells directly responded to LPS stimulation by activating the MAPK and NF-κB signaling pathways, and they produced IL-6 that promotes emergency granulopoiesis by phosphorylating C/EBPα and C/EBPβ, and this effect was suppressed by the action of an IL-6 receptor inhibitor. This work supports the finding that TLR is expressed on human hematopoietic stem and progenitor cells, and it provides evidence that human hematopoietic stem and progenitor cells can directly sense pathogens and produce cytokines exerting autocrine and/or paracrine effects, thereby promoting differentiation.

Objective The outcomes of antiplatelet therapy (APT) in patients with acute ischemic stroke (AIS) receiving endovascular therapy (EVT) remains controversial. Thus, we sought to make a systematic review and meta-analysis of recent clinical trials to confirm the safety and efficacy of APT. Methods All of clinical trails were systematically retrieved from PubMed, Embase and Cochrane. The endpoints or main outcome measures included symptomatic intracranial hemorrhage (sICH), 3-month mortality, successful recanalisation (SR) and 3-month functional independence (FI). Odd ratios (ORs) with their 95% confidence intervals (CIs) were calculated to synthesize effect size by using random-effects models. Sensitivity analysis was performed via calculation of rest data owiting one by one. Results 23 articles were included after screening. APT as an adjunct to EVT was associated with a higher likelihood of pooled successful recanalisation (OR 1.46, 95% CI 1.07–2.00) and 3-month FI (OR 1.24, 95% CI 1.01–1.51), no associated with sICH and 3-month mortality. However, Sensitivity analysis indicated that the association between APT and SR and 3-month FI were unstable. For patients with prior use of APT or receiving intravenous thrombolysis before EVT, no associated were found between APT and all of endpoints above. Conclusion Although adjuvant APT appears to increase the number of SR and 3-month FI, the results were unstable. Randomised controlled trials are needed to confirm the efficacy.

Uric acid is both a pro-oxidant and antioxidant. We investigated serum uric acid's association with mortality and aging biomarkers in older adults with varying levels of grip strength. A total of 5329 community-dwelling adults aged ≥55 years underwent assessments of serum uric acid levels, grip strength, and biomarkers of diverse physiological systems. The primary outcome was all-cause mortality. We observed a significant (P < .001) interaction between uric acid levels and grip strength on all-cause mortality risk. Among participants with low grip strength, a nonlinear association (P for nonlinearity = .006) was observed between serum uric acid levels and mortality risk after multivariate adjustment. Compared with participants with neither extreme uric acid levels nor low grip strength, those with a combination of high serum uric acid and low grip strength exhibited greater risks of mortality (adjusted hazard ratio [aHR], 1.52; 95% confidence interval [CI], 1.15–2.02) and deviations in biomarkers of specific systems, so did those with a combination of low serum uric acid and low grip strength (aHR, 1.52; 95% CI, 1.13–2.05). In conclusion, there was a J-shaped association between serum uric acid and the risk of all-cause mortality in older adults. This was primarily true for those with low grip strength.

To determine the effects of Chinese medicine (CM) involving triple rehabilitation therapy (中医三联康复疗法) on the progression of knee osteoarthritis (KOA). A total of 722 patients recruited from 38 community health service centers located in China from March 2013 to March 2017 were randomly divided into treatment and control groups equally, using a cluster randomization design. Health education combined with CM involving triple rehabilitation therapy for KOA (electro-acupuncture, Chinese medicinal herb fumigating-washing, and traditional exercises) was administered in the treatment group while conventional rehabilitation therapy (physical factor therapy, joint movement training, and muscle strength training) was administered in the control group. Patients with a visual analog scale (VAS) scores ≽4 were treated with dispersible meloxicam tablets (7.5 mg, once daily). The Lequesne index scores, VAS scores, range of motion (ROM), lower limb muscle strength, knee joint circumference, quantitative scores of KOA symptoms, and the short-form 36 item health survey questionnaire (SF-36) scores were measured for each patient at 5 checkpoints (before treatment, at the 2nd week and the 4th week during the 4-week treatment period, at 1 month and 3 months after end of treatment), and adverse reactions were observed also. A total of 696 patients completed the entire process, with 351 in the treatment group and 345 in the control group. At all treatment checkpoints, the treatment group demonstrated better outcomes than the control group with regard to the total Lequesne index scores, effective rate and improvement rate of the total Lequesne index scores, VAS scores, lower limb muscle strength, knee circumference, quantitative scores of KOA symptoms, and SF-36 scores as well (P

CircRNA‐0068481 and several miRNAs are important in the pathogenesis of right ventricular hypertrophy (VH), while the inhibition of eye absent transcriptional coactivator and phosphatase 3 (EYA3) was proved to reverse vascular remodelling in rats. In this study, we tried to study the diagnostic value and mechanistic role of circRNA_0068481 in the diagnosis of RVH in PAH patients. qPCR was done to measure circRNA‐0068481, miR‐646, miR‐750, miR‐885 and EYA3 mRNA expression. Luciferase assay was done to explore the regulatory relationship between circRNA‐0068481/EYA3 and the miRNAs. Western blot was done to measure EYA3 expression in AC16 cells. The expression of circRNA‐0068481, miR‐646 and miR‐570 showed a considerable capability to diagnose RVH in PAH patients. The luciferase activity of circRNA‐0068481 was remarkably suppressed by miR‐646, miR‐570 or miR‐885. The luciferase signal of EYA3 was also inhibited by miR‐646, miR‐570 and miR‐885. Up‐regulation of circRNA‐0068481 expression in AC16 significantly decreased miR‐646, miR‐570 and miR‐885 expression, and up‐regulated EYA3 expression, whereas circRNA‐0068481 down‐regulation significantly increased miR‐646, miR‐570 and miR‐885 expression, and repressed EYA3 expression. CircRNA_0068481 sponged several miRNAs including miR‐646, miR‐570 and miR‐885. These miRNAs were all found to target the expression of EYA3 mRNA, which is involved in the onset of right ventricular hypertrophy. Therefore, it can be concluded that the up‐regulation of circRNA_0068481 can predict the diagnosis of right ventricular hypertrophy in pulmonary arterial hypertension patients.

Background The outcomes of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) can improve with allogeneic hematopoietic stem cell transplantation (HSCT) during the first complete remission after treatment with a tyrosine kinase inhibitor (TKI) combined with chemotherapy. However, frail patients who are not eligible for allogeneic HSCT or those with TKI-resistant mutations within the BCR–ABL kinase domain have a poor clinical course. Blinatumomab (BLIN) is a bispecific T-cell engager antibody construct that directs cytotoxic T cells to CD19-expressing B-ALL cells. To date, only a few studies have shown the safety and efficacy of Blinatumomab (BLIN) + TKI combination therapy for relapsed/refractory (R/R) Ph+ ALL. Here we report the case of two patients with R/R Ph+ ALL who were treated with BLIN + TKI with durable molecular response. Case presentation Patient 1: A 69-year-old Japanese male with R/R Ph+ ALL was treated with conventional chemotherapy and dasatinib in April 2016. In May 2018, he developed molecular relapse due to the acquisition of T315I during dasatinib maintenance therapy. Thereafter, he achieved molecular complete remission (mCR) after switching from dasatinib to ponatinib. However, he developed a second relapse after the emergence of triple compound mutations (G250E/D276G/T315I) in November 2018. He subsequently received a total of nine cycles of BLIN and ponatinib combination therapy, which resulted in sustained mCR without any adverse events. Patient 2: A 69-year-old Japanese female with R/R Ph+ ALL was treated with chemotherapy and imatinib in April 2008. She developed molecular relapse due to the emergence of the T315I mutation in October 2017. She achieved mCR after switching from imatinib to ponatinib. However, she developed a second relapse after acquiring ABL exon4 skipping in addition to T315I. She subsequently received a total of seven cycles of BLIN and ponatinib combination therapy, which resulted in sustained mCR. Conclusion In our two cases, BLIN + ponatinib combination therapy was highly effective for R/R Ph+ ALL without any incidence of severe adverse events. Further studies with larger cohorts are warranted to validate the safety and efficacy of this potent combination therapy.

Two new flavones, namely 5-hydroxy-2-(4′-hydroxyphenyl)-6,12,13-trimethoxypyrano-xanthene-4,9-dione (1) and 5-hydroxy-2-(3′-methoxy-4′-hydroxyphenyl)-6-methoxy-11-isopropyl-pyranochromene-4,9-dione (2), were isolated from Salvia plebeia. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR spectral data. Compounds 1 and 2 were evaluated for their anti-angiogenic activities by the MTT assay with axitinib as positive control, and they displayed moderate anti-angiogenic activities with IC50 values of 14.07 and 11.25 μM, respectively.

Weixin Zhang,1 ChunMiao Xu,2 Jianyu Guo,3 Limei Guo,2 Hongliang Huo,4 Huan Wang5 1Department of Nursing, Qiqihar Medical University, Qiqihar, 161000, China; 2Department of Nursing of Medicine and Surgery, Qiqihar Medical University, Qiqihar, 161000, China; 3Department of Orthopedics Surgery, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, China; 4Department of Nursing, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, China; 5Department of Community Nursing, Qingdao Health School of Shandong Province, Qingdao, 266000, ChinaCorrespondence: ChunMiao Xu Tel +86 452 2664572Email mismbi@hotmail.comObjective: Glioma (GM) is a common type of malignant and aggressive tumor in brain with poor prognosis. Circular RNAs (circRNAs) are well-known regulators in cancer progression. However, its molecular basis in GM remains to be investigated.Materials and Methods: CircRNA microarray was used to detect differentially expressed circRNAs in GM and matched noncancerous tissues. qRT-PCR was applied to detect the expression profile of circ-ELF2 in GM tissue specimens and cell lines. CCK-8, clone formation, AO/EB staining, flow cytometry, wound healing, and transwell assays were performed to identify the functions of circ-ELF2 in GM cells. The distribution of circ-ELF2 was analyzed by RNA-FISH and subcellular fractionation assay. Dual-luciferase reporter assay was applied to verify the predicted binding sites between miR-510-5p and circ-ELF2/MUC15 3ʹ-UTR. Rescue assay was finally conducted to explore whether the oncogenic role of circ-ELF2 was partially attributed to miR-510-5p/MUC15 signaling.Results: We observed that circ-ELF2 was significantly upregulated in GM tissues, which was analyzed by circRNA microarray and qRT-PCR. Upregulation of circ-ELF2 was associated with poor prognosis and high recurrence rate for GM patients after surgery. The collapse of circ-ELF2 caused growth arrest and downregulation of cell migratory and invasive potential of GM cells and promoted cell apoptosis. In contrast, elevated expression of circ-ELF2 led to the opposite effect. Mechanistically, circ-ELF2 acted as a competing endogenous RNA (ceRNA) for miR-510-5p to positive modulate MUC15 expression at posttranscriptional level. Circ-ELF2 upregulated MUC15 by sponging miR-510-5p, thus promoting GM growth and aggressiveness.Conclusion: This study indicates that circ-ELF2/miR-510-5p/MUC15 signaling plays a key role in promoting the occurrence and development of GM.Keywords: glioma, circRNA, circ-ELF2, miR-510-5p, MUC15

Introduction Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous type of non-Hodgkin lymphoma with many molecular subtypes that can be distinguished by gene expression profiling (GEP). However, the pathogenesis of DLBCL is still unclear. Materials and methods The expression levels of the prolyl isomerase PIN-1 and other related proteins were determined in 73 primary DLBCL patient samples and cell lines by Western blotting (WB) and immunohistochemical (IHC) staining. Cell cycle and apoptosis were evaluated by flow cytometry. Lymphoma cell viability was detected by CCK-8 proliferation assay. Results High levels of PIN-1 expression were detected in 55% of germinal center B cell (GCB) DLBCL patient samples, whereas such abnormal expression levels were found in only 11% of non-GCB DLBCL patient samples. PIN-1 expression was positively associated with activation of the oncogenic phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway in both GCB DLBCL cell lines and primary patient samples. Depletion of PIN-1 was cytotoxic to GCB DLBCL model cell lines because it led to inhibition of the PI3K/AKT signaling pathway, revealing a GCB DLBCL subgroup that is dependent on this pathway. A PI3K inhibitor was selectively toxic to GCB DLBCL lines expressing high levels of PIN-1. Conclusion Our study used PIN-1 to identify a new subgroup of GCB DLBCL associated with the PI3K/AKT signaling pathway, and our findings reveal that inhibition of PI3K is a promising therapeutic approach for GCB DLBCL.

Resistin is an adipocytokine that is abundantly secreted from lipid cells and is related to the inflammatory process and cardiometabolic diseases. This study aimed to examine the role of resistin on inflammation and its effect on the clinical outcome of patients with atrial fibrillation (AF) following catheter ablation.A total of 108 patients (56.9 ± 12.0 years, 76.8% male) with symptomatic and drug-refractory AF undergoing catheter ablation were enrolled. Inflammatory biomarkers and epicardial fat volume by contrast computed tomography (CT) images were assessed in all patients before the procedure. Baseline resistin correlated with epicardial fat volume, tumor necrosis factor-α (TNF-α), and left atrial (LA) scar area. After the index procedure, the univariate analysis revealed that hypertension, persistent AF, LA diameter, and plasma resistin level were related to recurrent atrial arrhythmia. Multivariate regression analysis revealed that persistent AF, LA diameter, and plasma resistin level all independently predicted recurrent atrial arrhythmia after ablation. Plasma resistin with a level higher than 777 (pg/mL) could predict recurrence following catheter ablation of AF.High plasma resistin level is associated with poor left atrial substrate, high epicardial fat volume, and elevated TNF-α level in patients with AF. Plasma resistin may predict the recurrence of atrial arrhythmia after ablation.

Micro-transplantation (MST) by chemotherapy, combined with granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (GPBSC) infusion, from an HLA partial matched related donor has shown some encouraging effective therapy for acute myeloid leukemia (AML). However, the outcome of human leukocyte antigen (HLA) fully mismatched unrelated donor-derived MST in such patients is still unknown. In the present study, we compared the efficacy of HLA fully mismatched unrelated donor-derived MST, and partly matched related donor-derived MST, in AML of 126 patients from two centers in China, These patients, aged 16 to 65 years, were given three or four courses of MST, which consisted of a high dosage cytarabine followed by GPBSC from unrelated donor or related donor. There was a statistically significant difference in 3-year leukemia-free survival (LFS) and 3-year overall survival (OS) between the unrelated and the related group. The non-treatment-related mortality (NRM) rates of patients, and other adverse complications, were no different in the two groups. In conclusion, unrelated donor-derived MST is believed to be a safe treatment, with efficacy similar to or higher than related donor-derived MST. This result provides support for the potential of MST for expanding the donor selection. However, the specific mechanism of action needs further study.

Background Breast cancer stem cells (BCSCs) are typically seed cells of breast tumor that initiate and maintain tumor growth. MiR-7, as a cancer inhibitor, decreases the BCSC subset and inhibits tumor progression through mechanisms that remain unknown. Methods We examined miR-7 expression in breast cancer and developed a BCSC-driven xenograft mouse model, to evaluate the effects of miR-7 overexpression on the decrease of the BCSC subset in vitro and in vivo. In addition, we determined how miR-7 decreased the BCSC subset by using the ALDEFLUOR, lentivirus infection, dual-luciferase reporter, and chromatin immunoprecipitation-PCR assays. Results MiR-7 was expressed at low levels in breast cancer tissues compared with normal tissues, and overexpression of miR-7 directly inhibited lncRNA XIST, which mediates the transcriptional silencing of genes on the X chromosome, and reduced epithelium-specific antigen (ESA) expression by increasing miR-92b and inhibiting slug. Moreover, miR-7 suppressed CD44 and ESA by directly inhibiting the NF-κB subunit RELA and slug in breast cancer cell lines and in BCSC-driven xenografts, which confirmed the antitumor activity in mice injected with miR-7 agomir or stably infected with lenti-miR-7. Conclusions The findings from this study uncover the molecular mechanisms by which miR-7 inhibits XIST, modulates the miR-92b/Slug/ESA axis, and decreases the RELA and CD44 expression, resulting in a reduced BCSC subset and breast cancer growth inhibition. These findings suggest a potentially targeted treatment approach to breast cancer.

Benign recovery of carotenoids has been carried out on the calyx of Physalis alkekengi var. francheti by means of supercritical CO2 (SCCO2) extraction. The influences of extraction pressure, temperature and particle size on the time-dependent carotenoids yield are fully investigated and kinetically analyzed by using the hot-sphere model. The highest carotenoids yield recovered in 200 min is 15.96 mg/g raw sample, indicating that the calyx may be of great interest as valuable raw resources for the extraction of carotenoids. sThe SCCO2 extract has exhibited good antioxidant capacity as verified by radical-scavenging activity test results. The manufacturing cost (COM) for SCCO2 extraction of carotenoids from the calyx has been evaluated for scaling-up to the pilot plant at 40 MPa and 50 °C and a particle size of 0.114 mm. The effects of extraction capacities, labor wages, CO2 price and calyx-purchasing cost on COM have been analyzed. When using a capacity of 2 × 500 L and an extraction time of 60 min, the estimated specific COM can be US$ 687.96/t calyx or US$ 65.27/kg carotenoids, respectively. These calculation results turn to suggest that SCCO2 extraction is economically feasible to produce carotenoids form the herbal calyces.

Background Spontaneous formation of urinoma is a rare condition, especially for pregnant women. We report a patient in the third trimester of pregnancy with a spontaneous renal rupture who then develops a urinoma from urine leaking into the perinephric space. Case presentation A 23-year-old primagravida was diagnosed with a spontaneous renal rupture and acute left loin pain accompanied by hematuria when she was 35 weeks pregnant. A sub-capsular perinephric cyst then developed to a size of 319 × 175 × 253 mm, and because of discomfort to the patient, we performed Cesarean section. After a healthy male newborn was delivered, fluid was suctioned from a large perirenal cyst that had an estimated size of 300 × 200 × 300 mm. A percutaneous nephrostomy tube was left in the cyst until CT showed no remaining fluid. In the six-month follow-up, the patient showed no perirenal extravasation according to an ultrasound scan, and the urine analysis and renal function tests were normal. Conclusion Close follow-up should be recommended for the patient who has renal rupture after conservative therapy, especially for pregnant woman. CT or MRI should be considered in addition to utilizing ultrasound in the management of pregnant women who present with urinomas. Percutaneous nephrostomy is suggested as an appropriate treatment for large urinomas.

Objective: To investigate the clinical characteristics of familial hypercholesterolemia and early-onset acute coronary syndrome (ACS), in order to improve the understanding and diagnosis and treatment of the disease. Methods: We retrospectively studied the clinical data of 2 patients with familial hypercholesterolemia and premature acute coronary syndrome treated in the Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. All patients underwent genetic testing and coronary artery angiography. Results: Two patients were heterozygous familial hypercholesterolemia by gene test. Coronary artery angiography showed that three coronary arteries had serious lesions, which recovered well after drug and surgical treatment. Conclusion: Patients with familial hypercholesterolemia were prone to early onset of acute coronary syndrome, which should be identified, diagnosed and treated as soon as possible.

BackgroundAgenesis of the dorsal pancreas (ADP) is a rare disease, the pathogenic mechanism of which is partially related to variants of hepatocyte nuclear factor 1B (HNF1B) gene.Case PresentationWe report a case of ADP, which presented with acute ketoacidosis, hyperuricemia, and liver dysfunction. In this case, the HNF1B score was estimated as 16 and a heterozygous variant of HNF1B in exon 2 (c.513G>A-p.W171X) was identified through gene sequencing.ConclusionsA good understanding of the clinical comorbidities of ADP is essential for avoiding missed diagnosis to a great extent. Moreover, estimation of HNF1B score is recommended before genetic testing.

Objective: The fundus of the stomach is a challenging region for endoscopic resection of gastrointestinal stromal tumors (GISTs), especially in the anterior wall of the fornix at the side of the greater curvature. The aim of this study was to introduce using the “6”-turn of gastroscopy along the greater curvature wall (6TGS) technique in operation on the gastric fundus and provide evidence of its advantages.Methods: The clinical data of patients with stromal tumor in muscularis propria at the gastric fundus (STMF) at the Fourth Hospital of China Medical University between July 2016 and Dec 2020 were reviewed. The novel 6TGS technique was used in the procedure. The beneficial effects, suitability, applicable lesion site, influencing factors, and success rates of 6TGS were analyzed.Results: Ten cases in total were reviewed, and the 6TGS technique was successfully performed in 7 cases (70%). In all 7 patients, the gastroscope’s tip could access the location just below the gastric cardia, and all angles/sites of the fundus of the stomach could be operated on. The lesion was easily accessed, and the gastroscope was stable with good left-right movement ability and moderate forward and backward movement ability. Conclusion: 6TGS can improve the safety of gastroscopy resection of STMF and facilitate the excision of tumors in challenging sites in the gastric fundus. Patients need to be under general anesthesia with endotracheal intubation in the supine position to perform the 6TGS technique after distending the stomach with less air.

Background: The data on the relationship between statin use and clinical outcomes after intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) are in controversy.Objective: This systematic review and meta-analysis aimed to evaluate the safety and efficacy of statins administered prior to onset and during hospitalization in patients with AIS treated with IVT.Methods: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception until June 8, 2021. Comparative studies investigating statin effect on intracranial hemorrhage (ICH), functional outcomes, and mortality in adults with AIS treated with IVT were screened. Random-effect meta-analyses of odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were performed. The protocol was registered in PROSPERO (CRD42021254919).Results: Twenty-two observational studies were included, which involved 17,554 patients. The pooled estimates showed that pre-stroke statin use was associated with a higher likelihood of symptomatic ICH (OR 1.31; 95% CI 1.07–1.59; p = 0.008) and any ICH (OR 1.21; 95% CI 1.03–1.43; p = 0.02). However, the pre-stroke statin use was not significantly associated with the 3-month mortality, 3-month favorable functional outcome (FFO, modified Rankin Scale [mRS] score 0–1), and 3-month functional independence (FI; mRS score 0–2). However, in-hospital statin use was associated with a reduced risk of symptomatic ICH (OR 0.46; 95% CI 0.21–1.00; p = 0.045), any ICH (OR 0.51; 95% CI 0.27–0.98; p = 0.04), and 3-month mortality (OR 0.42; 95% CI 0.29–0.62; p < 0.001) and an increased probability of 3-month FFO (OR 1.33; 95% CI 1.02–1.744; p = 0.04) and 3-month FI (OR 1.41; 95% C, 1.11–1.80; p = 0.005).Conclusions: The present systematic review and meta-analysis suggests that in-hospital statin use after IVT may be safe and may have a favorable impact on clinical outcomes, a finding not observed in studies restricted to patients with pre-stroke statin use.

Objectives Aspirin has been suggested as a potential therapeutic strategy to prevent the growth and rupture of unruptured intracranial aneurysms (UIAs), but there is still controversy. The aim of this systematic review and meta–analysis is to determine the association between aspirin use and growth, rupture of UIAs. Methods We performed a systematic literature search of electronic databases to identify cohort and case–control studies investigating the relationship between aspirin use and growth or rupture of UIAs. Pooled odds ratio (OR) with corresponding 95% confidence interval (CI) were calculated using a random effects model. Heterogeneity among studies was quantified using the I2 statistic, and potential publication bias was assessed using funnel plots. Sensitivity analysis was performed to verify the robustness of the intention–to–treat results. Subgroup analysis was conducted according to the frequency of aspirin use. Results We identified 8 studies comprising 10,518 participants. The risk of bias was low to moderate. The pooled estimate showed that aspirin use was associated with a lower likelihood of growth of UIAs (OR = 0.25, 95% CI = 0.11–0.55; p = 0.0005) without statistical heterogeneity (p for Cochran Q statistic = 0.62, I2 = 0%). Likewise, aspirin intake also significant decreased 58% risk of intracranial aneurysms rupture (OR = 0.42, 95% CI = 0.29–0.60; p Conclusions The results of this systematic review and meta–analysis indicates a beneficial effect of aspirin on growth and rupture of UIAs.

A 53-year-old woman presented at our hospital due to nasal bleeding and petechiae with profound thrombocytopenia (0.4×109/L). Her platelet count returned to the normal range immediately following a platelet transfusion. In this case, tea brewed from Taxus yunnanensis was the only suspected agent ingested prior to the onset of thrombocytopenia while all other etiologies for thrombocytopenia were excluded. A re-exposure test to Taxus yunnanensis resulted in the recurrence of acute thrombocytopenia. The association of thrombocytopenia with substances other than drugs has so far only been rarely described and to the best of our knowledge, this is the first reported case of thrombocytopenia caused by Taxus yunnanensis.

Severe hepatic failure is rarely a cause of death in patients with immunoglobulin light chain (AL) amyloidosis. We herein report a case of AL amyloidosis involving a bleeding tendency due to factor X deficiency and marked hepatic involvement of amyloidosis. The patient died due to severe liver dysfunction two weeks after admission. The diagnosis was confirmed histologically by AL-λ amyloidosis, with the liver and spleen as the main lesions, on an autopsy. As treatment-related toxicity is strong in advanced cases, appropriate treatments are required to improve the prognosis of AL amyloidosis with severe liver dysfunction.

Breast cancer patients with high expression of aldehyde dehydrogenases (ALDHs) cell population have higher tolerability to chemotherapy since the cells posses a characteristic of breast cancer stem cells (BCSCs) that are resistant to conventional chemotherapy. In this study, we found that the ALDH‐positive cells were higher in CD44+CD24− and CD44+CD24−ESA+BCSCs than that in both BT549 and MDA‐MB‐231 cell lines but microRNA‐7 (miR‐7) level was lower in CD44+CD24− and CD44+CD24−ESA+BCSCs than that in MDA‐MB‐231 cells. Moreover, miR‐7 overexpression in MDA‐MB‐231 cells decreased ALDH1A3 activity by miR‐7 directly binding to the 3′‐untranslated region of ALDH1A3; while the ALDH1A3 expression was downregulated in MDA‐MB‐231 cells, the expressions of CD44 and Epithelium Specific Antigen (ESA) were reduced along with decreasing the BCSC subpopulation. Significantly, enforced expression of miR‐7 in CD44+CD24−ESA+BCSC markedly inhibited the BCSC‐driven xenograft growth in mice by decreasing an expression of ALDH1A3. Collectively, the findings demonstrate the miR‐7 inhibits breast cancer growth via suppressing ALDH1A3 activity concomitant with decreasing BCSC subpopulation. This approach may be considered for an investigation on clinical treatment of breast cancers., The aldehyde dehydrogenase (ALDH) positive cells were higher in CD44+CD24− and CD44+CD24−ESA+BCSCs than that in both BT549 and MDA‐MB‐231 cell lines but microRNA‐7 (miR‐7) level was lower in CD44+CD24− and CD44+CD24−ESA+BCSCs than that in MDA‐MB‐231 cells. MiR‐7 inhibits breast cancer growth via suppressing ALDH1A3 activity concomitant with decreasing BCSC subpopulation

Colloids and organics in shale gas fracturing flowback water (SGFFW) during shale gas extraction are of primary concerns. Coagulation combined with oxidation might be a promising process for SGFFW treatment. In this study, a novel electrocoagulation-peroxone (ECP) process was developed for SGFFW treatment by simultaneous coagulation and oxidation process with a Al plate as the anode and a carbon-PTFE gas diffusion electrode as the cathode, realizing the simultaneous processes of coagulation, H2O2 generation and activation by O3 at the cathode. Compared with electrocoagulation (EC) and peroxi-electrocoagulation (PEC), COD removal efficiency mainly followed the declining order of ECP, PEC and EC under the optimal current density of 50 mA cm−2. The appearance of medium MW fraction (1919 Da) during ozonation and PEC but disappearance in ECP indicated that these intermediate products couldn't be degraded by ozonation and PEC but could be further oxidized and mineralized by the hydroxyl radical produced by the cathode in ECP, demonstrating the hydroxyl radical might be responsible for the significant enhancement of COD removal. The pseudo-first order kinetic model can well fit ozonation and EC process but not the PEC and ECP process due to the synthetic effect of coagulation and oxidation. However, the proposed mechanism based model can generally fit ECP satisfactorily. The average current efficiency for PEC was 35.4% and 12% higher than that of ozonation and EC, respectively. This study demonstrated the feasibility of establishing a high efficiency and space-saving electrochemical system with integrated anodic coagulation and cathodic electro-peroxone for SGFFW treatment.

Although programmed cell death (PD)-1 blockade induces immune-related adverse events (irAEs), little is known about the safety of PD-1 blockade after allogeneic hematopoietic stem cell transplantation (HSCT). Here, we describe immune system changes during nivolumab-related myositis in a patient with Hodgkin's lymphoma after allogeneic HSCT; to our knowledge, this is the first such report in the literature. At the onset of myositis, the patient lost lower limb mobility against gravity, and had an activated immune profile with increased cytotoxic CD107a and granzyme B expression, as well as pro-inflammatory cytokines, interferon-γ, tumor necrosis factor-α, interleukin-2 in T and NK cells compared to healthy donor. Pulse steroid therapy decreased creatine kinase levels and induced PD-1 expression and regulatory T cells, but did not improve myositis; previously activated markers remained high. Four-week corticosteroid therapy decreased previously activated markers and the myositis improved. These findings provide new insights into nivolumab-induced irAE pathogenesis and suggest possible optimal treatments for irAEs.

The aim of this work was to determine whether chronic exposure to nonylphenol (NP), a representative substance of environmental endocrine disruptors (EEDs), at environmental concentration would have toxic effects on thyroid function and thyroid hyperplasia disease. Two hundred SPF Sprague-Dawley rats were divided into five groups (n = 40 per group): blank control group (corn oil), low-dose NP exposure group (0.4 mg/kg/d), medium-dose NP exposure group (4 mg/kg/d), high-dose NP exposure group (40 mg/kg/d), and estradiol control group (E2: 30 μg/kg/d). The rats were treated by gavage for 34 weeks, which were sampled twice (17 weeks and 34 weeks respectively). NP accumulation in the thyroid tissue (F = 52.93, P < 0.001) and serum (F = 5.54, P = 0.00) continuously increased in a significant dose-effect relationship. After NP exposure, the serum FT3 levels exhibited a dose-dependent increasing trend (F = 4.68, P = 0.01), while the serum FT4 level showed an opposite trend (F = 3.93, P= 0.01). Compared with the control group, hyperechoic areas (i.e., calcification points) were observed in the high-dose group. Follicular epithelial stratification was extremely severe, the monolayer cubic epithelial cells became flat, and the area of single follicles was even smaller in the high-dose group. In the high-dose NP group, there were numerous mitochondria that were severely swollen. The rough endoplasmic reticulum was abundant, with obvious expansion and vesiculation. The relative expression of ERα (F = 5.29, P = 0.00), ERβ (F = 10.17, P = 0.00), TRα (F = 7.71, P = 0.00), TRβ (F = 3.52.17, P = 0.02) and HMGB1 (F = 10.16, P = 0.01) proteins in the thyroid tissue in each NP exposure group was increased compared with the control group, and the relative expression of proteins increased if the exposure time was prolonged under the same exposure dose. Chronic exposure to NP at environmental concentration could have toxic effects on thyroid function, and induce thyroid hyperplasia disease in male rats.

Background: Patients with acute aortic dissection type A (AADA) often have hypoxemia (partial pressure of oxygen [PaO2]/fraction of inspired oxygen [FiO2] Methods: The medical records of 87 adult patients with AADA who underwent Sun's procedure and met the inclusion criteria (PaO2/FiO2 2, partial pressure of carbon dioxide, heart rate, respiratory rate, subjective discomfort, and reintubation rate were recorded. The difference in lung volume loss between the HFNC and COT groups was assessed using the radiological atelectasis score (chest radiograph) or calculated from three-dimensional (3D) reconstructed computed tomography (CT) images.Results: From day 1 to day 5 after weaning, there was no significant difference in PaO2/FiO2 between the HFNC and COT groups, although the FiO2 was significantly lower in the HFNC group than in the COT group (P < 0.05). Further studies indicated that the percentage of lung volume loss (pleural effusion and/or pulmonary atelectasis) by 3D reconstruction of CT images at 4–8 days post-operation was significantly lower in the HFNC group (P < 0.05). The subjective experience of breathing discomfort, reintubation rate, and length of stay in the ICU were significantly reduced in the HFNC group (P < 0.05). There was no significant difference in readmission to the ICU and in-hospital mortality between the two groups.Conclusions: HFNC can be used as an effective oxygen therapy for AADA patients with hypoxemia after Sun's procedure.

Severely immunosuppressed AIDS patients with recurrent opportunistic infections (OIs) represent an unmet medical need even in the era of antiretroviral therapy (ART). Here we report the development of a human leukocyte antigen (HLA)-mismatched allogeneic adaptive immune therapy (AAIT) for severely immunosuppressed AIDS patients. Twelve severely immunosuppressed AIDS patients with severe OIs were enrolled in this single-arm study. Qualified donors received subcutaneous recombinant granulocyte-colony-stimulating factor twice daily for 4–5 days to stimulate hematopoiesis. Peripheral blood mononuclear cells were collected from these donors via leukapheresis and transfused into the coupled patients. Clinical, immunological, and virological parameters were monitored during a 12-month follow-up period. We found AAIT combined with ART was safe and well-tolerated at the examined doses and transfusion regimen in all 12 patients. Improvements in clinical symptoms were evident throughout the study period. All patients exhibited a steady increase of peripheral CD4+ T cells from a median 10.5 to 207.5 cells/μl. Rapid increase in peripheral CD8+ T-cell count from a median 416.5 to 1206.5 cells/μl was found in the first 90 days since initiation of AAIT. In addition, their inflammatory cytokine levels and HIV RNA viral load decreased. A short-term microchimerism with donor cells was found. There were no adverse events associated with graft-versus-host disease throughout the study period. Overall, AAIT treatment was safe, and might help severely immunosuppressed AIDS patients to achieve a better immune restoration. A further clinical trial with control is necessary to confirm the efficacy of AAIT medication.

Gray zone lymphoma (GZL) is a rare type of B-cell lymphoma characterized by features of both diffuse large B-cell lymphoma and classical Hodgkin lymphoma (cHL). The prognosis of GZL is poorer than that of cHL and mediastinal large B-cell lymphoma. However, an optimal treatment strategy for relapsed/refractory (R/R) GZL has not been established in the clinical setting. The current study reported an excellent clinical response in a patient with R/R CD30-positive GZL who received brentuximab vedotin (BV) maintenance after autologous stem cell transplantation (ASCT). Although the patient was resistant to prior treatments, BV maintenance after ASCT achieved long-term remission. Hence, BV was determined to be a safe and effective therapeutic option for CD30-positive R/R GZL.

Background This study aimed to identify potential biomarkers associated with locoregional recurrence in patients with esophageal squamous cell carcinoma (ESCC) after radical resection. Methods We performed a quantitative proteomics analysis using isobaric tags for relative and absolute quantification (iTRAQ) with reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) to identify differential expression proteins (DEPs) between a locoregional recurrence group and good prognosis group of ESCC after radical esophagectomy. The bioinformatics analysis was performed with ingenuity pathway analysis software (IPA) and Gene Ontology (GO) database using the software of MAS 3.0. Kaplan-Meier (KM) Plotter Online Tool (http://www.kmplot.com) was used to evaluate the relationship between the differential expression of proteins and survival in patients with ESCC. Results More than 400 proteins were quantitated of which 27 proteins had upregulated expression and 55 proteins had downregulated expression in the locoregional recurrence group compared to the good prognosis group. These 82 DEPs were associated with biological procession of cancer development including cellular movement, cellular assembly and organization, cellular function and maintenance, cellular growth and proliferation, cell death and survival, DNA replication recombination and repair, and so on. Of these DEPs, SPTAN1 and AGT proteins were identified to be associated with RFS in ESCC. SPTAN1 was positively associated with RFS and AGT was negatively associated with RFS. Expression of SPTAN1 tended to have favorable OS while expression of AGT tended to have poor OS. Conclusions Our results demonstrated that quantitative proteomics is an effective discovery tool to identify biomarkers for prognosis prediction in ESCC. However, it needs more studies with large populations of ESCC to validate these potential biomarkers.