Case report on postoperative coagulation abnormalities.

RATIONALE: Intracranial aneurysm (IA) is defined as a localized dilation of cerebral arteries. With the continuous development of modern medical technology, surgery is still one of the main treatment methods. Although there are various postoperative complications, abnormal coagulation function is rare, especially those caused by lupus antibodies after surgery. The patient not only experienced postoperative abnormalities in coagulation function, but also discovered the presence of lupus anticoagulants in their body. Is the patient suffering from coagulation dysfunction caused by lupus anticoagulants, how is lupus anticoagulant produced, and what's special about treatment. With these questions in mind, we reviewed the entire treatment process of the patient. PATIENT CONCERNS: A 69-year-old woman presented with "headache and dizziness with neck pain" and was eventually diagnosed with IA hemorrhage. The patient underwent craniotomy under general anesthesia, and provided targeted support and treatment. Postoperative symptoms such as coma and intermittent fever occurred, and coagulation indicators were generally normal. After symptomatic support treatment, such as anti-infection treatment, the patient's temperature was gradually controlled. However, the abnormal clotting index and the efficacy of symptomatic therapeutic support, such as supplementation with coagulation factors, were not good. After further examination, the lupus anticoagulant was found, which provided us with a new treatment idea. DIAGNOSES: Coagulation disorders, postoperative IA, hypertension grade 3 (extremely high risk), coronary atherosclerotic atheropathy, and type 2 diabetes. INTERVENTIONS: The patient developed abnormal coagulation function after craniotomy, and symptomatic support treatment with coagulation factor supplementation and plasma infusion was ineffective. Finally, the lupus anticoagulant was found after a series of relevant examinations. After timely adjustment of the treatment plan, the patient's coagulation indices gradually improved. OUTCOMES: In this report, we present the case of a patient with abnormal coagulation function caused by the lupus anticoagulant after IA surgery. LESSONS: The coagulation function of the patient was abnormal after craniocerebral operation. After coagulation factor supplementation, the coagulation index of the patient was still not well improved. After further examination, the lupus anticoagulant was found. The treatment plan was actively adjusted, and the patient's condition gradually improved. Early recognition can allow doctors to provide appropriate therapy to patients.

Cytopenia after CAR­T cell therapy: Analysis of 63 patients with relapsed and refractory B­cell non­Hodgkin lymphoma.

The present study aimed to determine the clinical characteristics of cytopenia in patients with relapsed and refractory B-cell non-Hodgkin lymphoma (B-NHL) who were treated with chimeric antigen receptor T-cell (CAR-T) therapy. Thus, a total of 63 patients with relapsed and refractory B-NHL who underwent CAR-T therapy between March 2017 and October 2021 were retrospectively selected for analysis. Neutropenia, anemia and thrombocytopenia at grade ≥3 occurred in 48 (76.19%), 16 (25.39%) and 15 (23.80%) cases, respectively. The results of a multivariate analysis demonstrated that the baseline absolute neutrophil count (ANC) and hemoglobin concentration were independent risk factors for grade ≥3 cytopenia. A total of 3 patients died early and were therefore excluded from the present study. Furthermore, cell recovery was examined at day +28 after infusion; 21 patients (35%) did not recover from cytopenia and 39 patients (65%) recovered. A multivariate analysis demonstrated that the baseline ANC <2.29×109/l, baseline hemoglobin <114.50 g/l and baseline IL-6 >21.43 pg/l were independent risk factors affecting hemocyte recovery. In conclusion, patients with relapsed and refractory B-NHL exhibited an increased incidence of grade ≥3 hematologic toxicity following CAR-T cell therapy, while baseline blood cell and IL-6 levels are independent risk factors for hemocyte recovery.

Compressed Imaging Reconstruction Based on Block Compressed Sensing with Conjugate Gradient Smoothed l0 Norm.

Compressed imaging reconstruction technology can reconstruct high-resolution images with a small number of observations by applying the theory of block compressed sensing to traditional optical imaging systems, and the reconstruction algorithm mainly determines its reconstruction accuracy. In this work, we design a reconstruction algorithm based on block compressed sensing with a conjugate gradient smoothed l0 norm termed BCS-CGSL0. The algorithm is divided into two parts. The first part, CGSL0, optimizes the SL0 algorithm by constructing a new inverse triangular fraction function to approximate the l0 norm and uses the modified conjugate gradient method to solve the optimization problem. The second part combines the BCS-SPL method under the framework of block compressed sensing to remove the block effect. Research shows that the algorithm can reduce the block effect while improving the accuracy and efficiency of reconstruction. Simulation results also verify that the BCS-CGSL0 algorithm has significant advantages in reconstruction accuracy and efficiency.

A Structure-Based Iterative Closest Point Using Anderson Acceleration for Point Clouds with Low Overlap.

The traditional point-cloud registration algorithms require large overlap between scans, which imposes strict constrains on data acquisition. To facilitate registration, the user has to strategically position or move the scanner to ensure proper overlap. In this work, we design a method of feature extraction based on high-level information to establish structure correspondences and an optimization problem. And we rewrite it as a fixed-point problem and apply the Lie algebra to parameterize the transform matrix. To speed up convergence, we introduce Anderson acceleration, an approach enhanced by heuristics. Our model attends to the structural features of the region of overlap instead of the correspondence between points. The experimental results show the proposed ICP method is robust, has a high accuracy of registration on point clouds with low overlap on a laser datasets, and achieves a computational time that is competitive with that of prevalent methods.

Detection of aberrant DNA methylation patterns in sperm of male recurrent spontaneous abortion patients.

Aberrant DNA methylation patterns in sperm are a cause of embryonic failure and infertility, and could be a critical factor contributing to male recurrent spontaneous abortion (RSA). The purpose of this study was to reveal the potential effects of sperm DNA methylation levels in patients with male RSA. We compared sperm samples collected from fertile men and oligoasthenospermia patients. Differentially methylated sequences were identified by reduced representation bisulfite sequencing (RRBS) methods. The DNA methylation levels of the two groups were compared and qRT-PCR was used to validate the expression of genes showing differential methylation. The results indicated that no difference in base distribution was observed between the normal group and the patient group. However, the chromosome methylation in these two groups was markedly different. One site was located on chromosome 8 and measured 150 bp, while the other sites were on chromosomes 9, 10, and X and measured 135 bp, 68 bp, and 136 bp, respectively. In particular, two genes were found to be hypermethylated in these patients, one gene was DYDC2 (placed in the differential methylation region of chromosome 10), and the other gene was NXF3 (located on chromosome X). Expression levels of DYDC2 and NXF3 in the RSA group were significantly lower than those in the normal group (P < 0.05). Collectively, these results demonstrated that changes in DNA methylation might be related to male RSA. Our findings provide important information regarding the potential role of sperm DNA methylation in human development.

Retraction of "Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating microRNA-34a-5p/NOTCH1 signaling pathway".

[This retracts the article DOI: 10.1515/biol-2020-0025.].

[Expression and Clinical Significance of EZH2 in Patients with Diffuse Large B Cell Lymphoma Accompanied by HBV Infection].

OBJECTIVE: To explore the expression and clinical significance of EZH2 in DLBCL patients accompanied by HBV infection. METHODS: The clinicopathological data of 59 patients with DLBCL accompanied by HBV infection in our hospital from February 2015 to October 2017 were analyzed retrospectively. The patients were divided into HBV negative and HBV positive groups by serological testing before surgery. The expression of EZH2 was detected by immumohistochemical staining, and the clinicopathological characteristics and survival were analyzed and compared between these two groups. RESULTS: There were 30 patients (50.8%) in the HBV negative group and 29 patients (49.2%)in the HBV positive group. The differences of age, LDH level and IPI score between two groups were statistically significant (P＜0.05). The expression of EZH2 in HBV- positive group was significantly higher than that in the HBV- negative group (P＜0.05), where the expression of EZH2 correlated with the expression of the BCL-6 (r=0.282, P＜0.05), especially in the GCB-DLBCL (r=0.549, P＜0.05). PFS was not significantly different between two groups of HBV (P＞0.05), while the PFS in the R-CHOP regimen group was higher than that in the CHOP regimen group (P＜0.05). COX multivariate analysis showed that both the chemotherapy regimen without R and the increased level of LDH were the risk factors affecting the prognosis of DLBCL patients (P＜0.05). CONCLUSION: EZH2 highly expresses in HBV positive group, suggesting that the significance of EZH2 in DLBCL with HBV infection is worth further explore.

[Clinical Features of Infection within 100 days after Hematopoietic Stem Cell Transplantation in 313 patients with Hematologic Diseases].

OBJECTIVE: To analyze the clinical characteristics of infection within 100 days after hematopoietic stem cell transplantation (HSCT) in patients with hematologic disease. METHODS: The culture results of 313 HSCT patients infected in the hematology department of our hospital from January 2013 to January 2019 were collected, and the infection incidence, pathogen distribution, drug susceptibility test results and infection risk factors out of them all were analyzed. RESULTS: Among 313 HSCT patients, infection occurred within 100 days in 262(83.7%) patients, 234 (89.3%) cases were in neutropenic period at infection onset. 156 pathogen distributions showed that the bloodstream infection (64.1%) ranked first. Among isolates, Gram-negative bacteria was 86 (55.1%), which were higher than Gram-positive bacteria (49, 31.4%), and fungi was 21(13.5%). The prevalence of ESBLs in E.coli and Klebsiella pneumoniae were 36.4% and 31.6%, respectively. The drug resistance rates of E.coli and Klebsiella pneumoniae to carbapenems were 18.20% and 5.3%, respectively, and to amikacin were 29.5% and 10.5%, respectively. The antimicrobial resistance of fermentation bacteria was significantly different. The drug resistence rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenems were high. Only one strain of methicillin-resistant staphylococcus aureus (MRSA) was found. The drug resistence rates of enterococcus faecalis to linezolid was 14.30%. The sensitivity of other Gram-positive bacteria to vancomycin, teicolanin and linezolid was 100%. The HSCT in our hospital was mainly allogeneic, and univariate analysis showed that the risk factors for infection were status before trasplantion, HLA matching type,length of stay for the first transplant, and length of neutropenia, while Mulvariate analysis showed that only HLA matching type showed statistical significance. CONCLUSION: The infection of patients after HSCT occurrs in period of neutropenia, Most of pathogens are G- bacteria, and the resistance to antibiotics is quite common, HLA mismatch is allo-HSCT independent risk factors for infection. It is very imprtant to monitor actively the distribution of pathogenic bacteria, drug-resistance and risk factors of infection for guiding more reasonable and standardized clinical treatment.

Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathway.

Multiple myeloma (MM) is a serious health issue in hematological malignancies. Long non-coding RNA taurine-upregulated gene 1 (TUG1) has been reported to be highly expressed in the plasma of MM patients. However, the functions of TUG1 in MM tumorigenesis along with related molecular basis are still undefined. In this study, increased TUG1 and decreased microRNA-34a-5p (miR-34a-5p) levels in MM tissues and cells were measured by the real-time quantitative polymerase reaction assay. The expression of relative proteins was determined by the Western blot assay. TUG1 knockdown suppressed cell viability, induced cell cycle arrest and cell apoptosis in MM cells, as shown by Cell Counting Kit-8 and flow cytometry assays. Bioinformatics analysis, luciferase reporter assay, and RNA pull-down assay indicated that miR-34a-5p was a target of TUG1 and directly bound to notch receptor 1 (NOTCH1), and TUG1 regulated the NOTCH1 expression by targeting miR-34a-5p. The functions of miR-34a-5p were abrogated by TUG1 upregulation. Moreover, TUG1 loss impeded MM xenograft tumor growth in vivo by upregulating miR-34a-5p and downregulating NOTCH1. Furthermore, TUG1 depletion inhibited the expression of Hes-1, Survivin, and Bcl-2 protein in MM cells and xenograft tumors. TUG1 knockdown inhibited MM tumorigenesis by regulating the miR-34a-5p/NOTCH1 signaling pathway in vitro and in vivo, deepening our understanding of the TUG1 function in MM.

Chitosan oligosaccharides prevent doxorubicin-induced oxidative stress and cardiac apoptosis through activating p38 and JNK MAPK mediated Nrf2/ARE pathway.

Doxorubicin (DOX) is one of the most effective chemotherapeutic drugs; however, the incidence of cardiotoxicity compromises its therapeutic index. Oxidative stress and apoptosis are believed to be involved in DOX-induced cardiotoxicity. Chitosan oligosaccharides (COS), the enzymatic hydrolysates of chitosan, have been reported to possess diverse biological activities including antioxidant and anti-apoptotic properties. The objective of the present study was to investigate the potential role of COS against DOX-induced cardiotoxicity, and the effects of COS on apoptosis and oxidative stress in rats and H9C2 cells. Furthermore, we also shed light on the involved pathways during the whole process. For this purpose, first, we demonstrated that COS exhibited a significant protective effect on cardiac tissue by not only inducing a decrease in body and heart growth but also ameliorated oxidative damage and ECG alterations in DOX-treated rats. Second, we found that COS reversed the decrease of cell viability induced by DOX, reduced the intracellular reactive oxygen species (ROS), increased the mitochondrial membrane potential (MMP) and Bcl-2/Bax ratio. COS treatment also results in reduced caspase-3 and caspase-9 expressions, and an increase in the phosphorylation of MAPKs (mitogen-activated protein kinases) in DOX-exposed H9C2 cells. Additionally, cellular homeostasis was re-established via stabilization of MAPK mediated nuclear factor erythroid 2-related factor 2/antioxidant-response element (Nrf2/ARE) signaling and transcription of downstream cytoprotective genes. In summary, these findings suggest that COS could be a potential candidate for the prevention and treatment of DOX-induced cardiotoxicity.

Tumor necrosis factor receptor 2 may promote the proliferation and drug resistance of Kapras299 and L428 lymphoma cells via the AKT and WNT/ß-catenin signaling pathways.

Circulating soluble tumor necrosis factor receptor 2 (sTNFR2) has been associated with a relatively poor prognosis in various types of lymphoma. However, the specific role of TNFR2 expression in lymphoma cells remains uncharacterized. In the present study, TNFR2 expression was quantified in the Hodgkin lymphoma cell line, L428, and the anaplastic large-cell lymphoma cell line, Karpas299, using RT-PCR and western blot analyses. Karpas299 cells exhibited higher TNFR2 expression than L428 cells. Proliferation and drug resistance experiments demonstrated that Karpas299 cells also possessed a greater proliferative ability and resistance to adriamycin (ADM) than L428 cells, with 50% inhibitory concentrations (IC50) of 1.423±0.24 µmol/l for Karpas299 cells, compared with 0.728±0.15 µmol/l for L428 cells (P<0.05). The knockdown of TNFR2 in Karpas299 cells significantly reduced their proliferative ability; when treated with ADM, the cell inhibition rate increased from 49.34±5.42% to 74.13±6.81% (P<0.05). The upregulation of TNFR2 in L428 cells significantly increased their proliferative ability; when treated with ADM, the cell inhibition rate decreased from 47.03±5.25% to 28.71±4.90% (P<0.05). Investigation of the underlying molecular mechanism indicated that the upregulation of TNFR2 expression in L428 cells increased the expression of ß-catenin and the phosphorylation of AKT. In L428 cells overexpressing TNFR2, the ß-catenin blocker, DKK1, or the AKT inhibitor, LY294002, abrogated the increase in proliferation induced by TNFR2 and increased cell inhibition rate upon treatment with ADM. In summary, the present study demonstrated that TNFR2 promoted the proliferative and drug resistance abilities of lymphoma cells via the AKT and WNT/ß-catenin signaling pathways. This may provide the experimental basis for the further study of TNFR2 activity in lymphoma cells and warrant its investigation as a therapeutic target for lymphoma.

[Association of abnormal length of Y chromosome with semen quality and outcome of assisted reproductive technology in humans].

OBJECTIVE: To investigate the association of the abnormal length of human Y chromosome with semen quality and the outcome of assisted reproductive technology (ART). METHODS: Based on the karyotype, we assigned the patients undergoing ART to a normal control, a long Y chromosome (Y>18), and a short Y chromosome group (Y<22). We compared the semen parameters and numbers of embryos and high-quality embryos among the three groups of patients and performed statistical analysis of the obtained data using Chi-square distribution and t-test. RESULTS: Compared with the control, the Y>18 group showed a significantly lower incidence rate of asthenozoospermia (31.03% vs 8.33%, P <0.05) and a larger number of high-quality embryos (5.46 ± 4.54 vs 7.40 ± 5.49, P<0.05). Both the incidence rate of azoospermia and number of total embryos were remarkably lower in the control than in the Y<22 group (1.87% vs 16.47%, P <0.05; 8.60 ± 7.03 vs 10.00 ± 6.58, P<0.05). No statistically significant differences were found in the pregnancy rate between the Y>18 and Y<22 groups (P>0.05). CONCLUSIONS: Short Y chromosome may affect spermatogenesis, but the length of Y chromosome does not negatively influence the outcome of ART.

Clematichinenoside inhibits VCAM-1 and ICAM-1 expression in TNF-α-treated endothelial cells via NADPH oxidase-dependent IκB kinase/NF-κB pathway.

Proinflammatory cytokine TNF-α-induced adhesion of leukocytes to endothelial cells plays a critical role in the early stage of atherosclerosis. Oxidative stress and redox-sensitive transcription factors are implicated in the process. Thus, compounds that mediate intracellular redox status and regulate transcription factors are of great therapeutic interest. Clematichinenoside (AR), a triterpene saponin isolated from the root of Clematis chinensis Osbeck, was previously demonstrated to have anti-inflammatory and antioxidative properties. However, little is known about the exact mechanism underlying these actions. Thus we performed a detailed study on its effect on leukocytes-endothelial cells adhesion with TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) and cell-free systems. First, we found that AR reduced TNF-α-induced VCAM-1 and ICAM-1 expression and their promoter activity, inhibited translocation of p65 and phosphorylation of IκBα, suppressed IκB kinase-ß (IKK-ß) activity, lowered O2(∙-) and H2O2 levels, tackled p47(phox) translocation, and decreased NOX4 NADPH oxidase expression. Second, we showed that AR exhibited no direct free radical scavenging ability in cell-free systems at concentrations that were used in intact cells. Besides, AR had no direct effect on the activity of IKK-ß that was extracted from TNF-α-stimulated HUVECs. We also found that p47 translocation, NOX4 expression, and reactive oxygen species (ROS) levels were up-regulated before IκB phosphorylation in TNF-α-induced HUVECs. Moreover, TNF-α-enhanced IKK-ß activity was also inhibited by (polyethylene glycol) PEG-catalase, N-acetylcysteine (NAC), and vitamin E. In conclusion, these results suggest that AR reduces VCAM-1 and ICAM-1 expression through NADPH oxidase-dependent IKK/NF-κB pathways in TNF-α-induced HUVECs, which finally suppress monocyte-HUVECs adhesion. This compound is potentially beneficial for early-stage atherosclerosis.