Identification of UDP-glucuronosyltransferase (UGT) isoforms involved in the metabolism of Chlorophenols (CPs).

Chlorophenols (CPs) are a group of pollutants that pose a great threat to the environment, they are widely used in industrial and agricultural wastes, pesticides, herbicides, textiles, pharmaceuticals and plastics. Among CPs, pentachlorophenol was listed as one of the persistent organic pollutants (POPs) by the Stockholm convention. This study aims to identify the UDP-glucosyltransferase (UGT) isoforms involved in the metabolic elimination of CPs. CPs' mono-glucuronide was detected in the human liver microsomes (HLMs) incubation mixture with co-factor uridine-diphosphate glucuronic acid (UDPGA). HLMs-catalyzed glucuronidation metabolism reaction equations followed Michaelis-Menten or substrate inhibition type. Recombinant enzymes and chemical reagents inhibition experiments were utilized to phenotype the main UGT isoforms involved in the glucuronidation of CPs. UGT1A6 might be the major enzyme in the glucuronidation of mono-chlorophenol isomer. UGT1A1, UGT1A6, UGT1A9, UGT2B4 and UGT2B7 were the most important five UGT isoforms for metabolizing the di-chlorophenol and tri-chlorophenol isomers. UGT1A1 and UGT1A3 were the most important UGT isoforms in the catalysis of tetra-chlorophenol and pentachlorophenol isomers. Species differences were investigated using rat liver microsomes (RLMs), pig liver microsomes (PLMs), dog liver microsomes (DLMs), and monkey liver microsomes (MyLMs). All these results were helpful for elucidating the metabolic elimination and toxicity of CPs.

Nicorandil-Pretreated Mesenchymal Stem Cell-Derived Exosomes Facilitate Cardiac Repair After Myocardial Infarction via Promoting Macrophage M2 Polarization by Targeting miR-125a-5p/TRAF6/IRF5 Signaling Pathway.

Background: Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI). Methods: MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism. Results: Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway. Conclusion: This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation.

Effect of repetitive transcranial magnetic stimulation-assisted training on lower limb motor function in children with hemiplegic cerebral palsy.

OBJECTIVE: To explore the effect of repetitive transcranial magnetic stimulation (rTMS)-assisted training on lower limb motor function in children with hemiplegic cerebral palsy (HCP). METHOD: Thirty-one children with HCP who met the inclusion criteria were selected and randomly divided into a control group (n = 16) and an experimental group (n = 15). The control group received routine rehabilitation treatment for 30 min each time, twice a day, 5 days a week for 4 weeks. Based on the control group, the experimental group received rTMS for 20 min each time, once a day, 5 days a week for 4 weeks. The outcome measures included a 10-metre walk test (10MWT), a 6-minute walk distance (6MWD) test, D- and E-zone gross motor function measurements (GMFM), the symmetry ratio of the step length and stance time and the muscle tone of the triceps surae and the hamstrings (evaluated according to the modified Ashworth scale), which were obtained in both groups of children before and after treatment. RESULTS: After training, the 10MWT (P < 0.05), 6MWD (P < 0.01), GMFM (P < 0.001) and the symmetry ratio of the step length and stance time of the two groups were significantly improved (P < 0.05), there was more of an improvement in the experimental group compared with the control group. There was no significant change in the muscle tone of the hamstrings between the two groups before and after treatment (P > 0.05). After treatment, the muscle tone of the triceps surae in the experimental group was significantly reduced (P < 0.05), but there was no significant change in the control group (P > 0.05). CONCLUSION: Repetitive TMS-assisted training can improve lower limb motor function in children with HCP.

Levosimendan Reverses Cardiac Malfunction and Cardiomyocyte Ferroptosis During Heart Failure with Preserved Ejection Fraction via Connexin 43 Signaling Activation.

PURPOSE: In recent decades, the occurrence of heart failure with preserved ejection fraction (HFpEF) has outweighed that of heart failure with reduced ejection fraction by degrees, but few drugs have been demonstrated to improve long-term clinical outcomes in patients with HFpEF. Levosimendan, a calcium-sensitizing cardiotonic agent, improves decompensated heart failure clinically. However, the anti-HFpEF activities of levosimendan and underlying molecular mechanisms are unclear. METHODS: In this study, a double-hit HFpEF C57BL/6N mouse model was established, and levosimendan (3 mg/kg/week) was administered to HFpEF mice aged 13 to 17 weeks. Different biological experimental techniques were used to verify the protective effects of levosimendan against HFpEF. RESULTS: After four weeks of drug treatment, left ventricular diastolic dysfunction, cardiac hypertrophy, pulmonary congestion, and exercise exhaustion were significantly alleviated. Junction proteins in the endothelial barrier and between cardiomyocytes were also improved by levosimendan. Among the gap junction channel proteins, connexin 43, which was especially highly expressed in cardiomyocytes, mediated mitochondrial protection. Furthermore, levosimendan reversed mitochondrial malfunction in HFpEF mice, as evidenced by increased mitofilin and decreased ROS, superoxide anion, NOX4, and cytochrome C levels. Interestingly, after levosimendan administration, myocardial tissue from HFpEF mice showed restricted ferroptosis, indicated by an increased GSH/GSSG ratio; upregulated GPX4, xCT, and FSP-1 expression; and reduced intracellular ferrous ion, MDA, and 4-HNE levels. CONCLUSION: Regular long-term levosimendan administration can benefit cardiac function in a mouse model of HFpEF with metabolic syndromes (namely, obesity and hypertension) by activating connexin 43-mediated mitochondrial protection and sequential ferroptosis inhibition in cardiomyocytes.

Efficacy of CLAE Chemotherapy Regimen Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the efficacy and safety of CLAE intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed/refractory acute leukemia (R/R AL).@*METHODS@#CLAE regimen [cladribine 5 mg/(m2·d), d 1-5; cytarabine 1.5 g/(m2·d), d 1-5; etoposide 100 mg/(m2·d), d 3-5] followed by allo-HSCT was used to treat 3 R/R AL patients. The patients received CLAE chemotherapy in relapsed or refractory status and underwent bone marrow puncture to judge myelodysplastic state. After an interval of 3 to 5 days, followed by preconditioning regimen for allo-HSCT [fludarabine 30 mg/(m2·d), d -7 to d -3; busulfan 0.8 mg/kg q6h, d -6 to d -3 or d -5 to d -2. If the bone marrow hyperplasia was not active and the blasts were less than 10%, busulfan should be used for 3 days. If the bone marrow hyperplasia was active and the blasts were more than 10%, busulfan should be used for 4 days]. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were used for graft-versus-host disease (GVHD) prevention. After transplantation, the status of minimal residual disease (MRD) and bone marrow chimerism were regularly monitored in all 3 patients, and demethylation drugs or dasatinib were used to prevent recurrence 3 months after transplantation.@*RESULTS@#2 patients with t(11;19) translocation and relapse/refractory acute myeloid leukemia recurred within 6 months after induction of remission, and received intensive chemotherapy with CLAE regimen followed by haploidentical allo-HSCT and unrelated donor allo-HSCT, respectively. The two patients both relapsed 6 months after transplantation, then achieved complete remission by donor lymphocyte infusion, interferon, interleukin-2 and other methods, and disease-free survival was 2 years after transplantation. The other patient was chronic myelogenous leukemia who developed acute lymphoblastic leukemia during oral administration of tyrosine kinase inhibitor, accompanied by T315I and E255K mutations in ABL1 kinase region and additional chromosomal abnormalities. After morphological remission by induction chemotherapy, central nervous system leukemia was complicated. Intensive chemotherapy with CLAE regimen followed by sibling allo-HSCT was performed in the positive state of MRD. The patient relapsed 3 months after transplantation, and achieved remission after chimeric antigen receptor T-cell (CAR-T) therapy, however, he died 5 months after transplantation because of severe cytokine release syndrome (CRS) and GVHD.@*CONCLUSION@#CLAE regimen followed by allo-HSCT may be an effective salvage treatment option for R/R AL patients to prolong the overall survival.

Research progress on stable gene transfection methods of Plasmodium falciparum / 中国热带医学

@#Abstract: Transfection of Plasmodium falciparum is helpful to study the function of its genes, such as drug resistance. However, transgenic manipulation has been very challenging, mainly due to the high A/T base sequence structure (A+T content of about 82%) and low transfection efficiency of the Plasmodium genome. Electroporation-based transfection of Plasmodium falciparum has been successfully applied in the study of certain genes, and electroporation by preloading is currently the preferred method for introducing foreign DNA into Plasmodium falciparum. The site-directed editing of Plasmodium genes mostly adopts the method of two-plasmid transfection. It is generally believed that successful transfection of Plasmodium requires a large amount of high-purity plasmid DNA and an accurate transfection system. In addition to the evaluation of the current commonly used electrotransfection methods, this paper also introduces a new transfection method, namely lyse-reseal erythrocytes for transfection (LyRET). This paper also review the role of factors such as plasmid DNA concentration, the use of transfection reagents, the setting of transfection parameters, the addition of fresh red blood cells, and the markers of successful transfection in improving the success rate and efficiency of Plasmodium transfection, in the hope of providing a reference for study in this field.

Mendelian randomization study of causal link from gut microbiota to colorectal cancer.

Recent studies have shown the relevance of gut microbiota in the occurrence and development of colorectal cancer (CRC), but the causal relationship remains unclear in the human population. The present study aims to assess the causal relationship from the gut microbiota to CRC and to identify specific causal microbe taxa via genome-wide association study (GWAS) summary statistics based two-sample Mendelian randomization (MR) analyses. Microbiome GWAS (MGWAS) in the TwinsUK 1,126 twin pairs was used as discovery exposure sample, and MGWAS in 1,812 northern German participants was used as replication exposure sample. GWAS of CRC in 387,156 participants from the UK Biobank (UKB) was used as the outcome sample. Bacteria were grouped into taxa features at both family and genus levels. In the discovery sample, a total of 30 bacteria features including 15 families and 15 genera were analyzed. Five features, including 2 families (Verrucomicrobiaceae and Enterobacteriaceae) and 3 genera (Akkermansia, Blautia, and Ruminococcus), were nominally significant. In the replication sample, the genus Blautia (discovery beta=-0.01, P = 0.04) was successfully replicated (replication beta=-0.18, P = 0.01) with consistent effect direction. Our findings identified genus Blautia that was causally associated with CRC, thus offering novel insights into the microbiota-mediated CRC development mechanism.

Impact of percutaneous coronary intervention on chronic total occlusion in the non-infarct-related artery in patients with STEMI: a systematic review and meta-analysis.

OBJECTIVES: We sought to compare the clinical outcomes between culprit-only percutaneous coronary intervention (PCI) versus multivessel PCI (MV-PCI) in patients with ST-segment elevation myocardial infarction (STEMI) accompanied by chronic total occlusion (CTO) in the non-infarct-related artery(non-IRA). DESIGN: Studies that compared culprit-only PCI versus MV-PCI in patients with STEMI accompanied by CTO in the non-IRA were included. Random odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: Eight studies with 2,259 patients were included. The results suggested that in patients with STEMI accompanied by CTO in the non-IRA, culprit-only PCI was associated with higher risks of all-cause mortality (OR: 2.89; 95% CI: 2.09-4.00; I2 = 0.0%), cardiac death (OR: 3.12; 95% CI: 2.05-4.75; I2 = 16.8%), stroke (OR: 2.80; 95% CI: 1.04-7.53; I2 = 0.0%), major adverse cardiovascular event (MACE; OR: 2.06; 95% CI: 1.39-3.06; I2 = 54.0%), and heart failure (OR: 1.99; 95% CI: 1.22-3.24; I2 = 0.0%) compared with staged MV-PCI, which were mainly derived from retrospective studies. No differences were observed in myocardial infarction or revascularization. Pooled multivariable adjusted results consistently indicated that staged MV-PCI was superior to culprit-only PCI. CONCLUSIONS: For patients with STEMI accompanied by CTO in the non-IRA, staged MV-PCI may be better compared with culprit-only PCI due to potential reduced risks of all-cause mortality, cardiac death, stroke, MACE, and heart failure. Meanwhile, further randomized trials are warranted to confirm or refute our findings.

Spatiotemporal absorption fluctuation imaging based on U-Net.

SIGNIFICANCE: Full-field optical angiography is critical for vascular disease research and clinical diagnosis. Existing methods struggle to improve the temporal and spatial resolutions simultaneously. AIM: Spatiotemporal absorption fluctuation imaging (ST-AFI) is proposed to achieve dynamic blood flow imaging with high spatial and temporal resolutions. APPROACH: ST-AFI is a dynamic optical angiography based on a low-coherence imaging system and U-Net. The system was used to acquire a series of dynamic red blood cell (RBC) signals and static background tissue signals, and U-Net is used to predict optical absorption properties and spatiotemporal fluctuation information. U-Net was generally used in two-dimensional blood flow segmentation as an image processing algorithm for biomedical imaging. In the proposed approach, the network simultaneously analyzes the spatial absorption coefficient differences and the temporal dynamic absorption fluctuation. RESULTS: The spatial resolution of ST-AFI is up to 4.33 µm, and the temporal resolution is up to 0.032 s. In vivo experiments on 2.5-day-old chicken embryos were conducted. The results demonstrate that intermittent RBCs flow in capillaries can be resolved, and the blood vessels without blood flow can be suppressed. CONCLUSIONS: Using ST-AFI to achieve convolutional neural network (CNN)-based dynamic angiography is a novel approach that may be useful for several clinical applications. Owing to their strong feature extraction ability, CNNs exhibit the potential to be expanded to other blood flow imaging methods for the prediction of the spatiotemporal optical properties with improved temporal and spatial resolutions.

A transcriptome-wide association study identifies susceptibility genes for Parkinson's disease.

Genome-wide association study (GWAS) has seen great strides in revealing initial insights into the genetic architecture of Parkinson's disease (PD). Since GWAS signals often reside in non-coding regions, relatively few of the associations have implicated specific biological mechanisms. Here, we aimed to integrate the GWAS results with large-scale expression quantitative trait loci (eQTL) in 13 brain tissues to identify candidate causal genes for PD. We conducted a transcriptome-wide association study (TWAS) for PD using the summary statistics of over 480,000 individuals from the most recent PD GWAS. We identified 18 genes significantly associated with PD after Bonferroni corrections. The most significant gene, LRRC37A2, was associated with PD in all 13 brain tissues, such as in the hypothalamus (P = 6.12 × 10-22) and nucleus accumbens basal ganglia (P = 5.62 × 10-21). We also identified eight conditionally independent genes, including four new genes at known PD loci: CD38, LRRC37A2, RNF40, and ZSWIM7. Through conditional analyses, we demonstrated that several of the GWAS significant signals on PD could be driven by genetically regulated gene expression. The most significant TWAS gene LRRC37A2 accounts for 0.855 of the GWAS signal at its loci, and ZSWIM7 accounts for all the GWAS signals at its loci. We further identified several phenotypes previously associated with PD by querying the single nucleotide polymorphisms (SNPs) in the final model of the identified genes in phenome databases. In conclusion, we prioritized genes that are likely to affect PD by using a TWAS approach and identified phenotypes associated with PD.

Does multivessel revascularization fit all patients with STEMI and multivessel coronary artery disease? A systematic review and meta-analysis.

OBJECTIVE: We sought to assess the relative merits of different revascularization strategies in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease complicated by cardiogenic shock or chronic total occlusion (CTO). BACKGROUND: Recent randomized trials and meta-analysis have suggested that multivessel percutaneous coronary intervention (PCI) is associated with better outcomes in patients with STEMI and multivessel coronary artery disease, however, patients complicated by cardiogenic shock or CTO were excluded. METHODS: Studies that compared multivessel PCI (immediate or staged) with culprit-only PCI in patients with STEMI and multivessel coronary artery disease complicated by cardiogenic shock or CTO were included. Random odd ratio (OR) and 95% confidence interval (CI) were conducted. RESULTS: Sixteen studies with 8695 patients complicated by cardiogenic shock and eight studies with 2259 patients complicated by CTO were included. In patients complicated by cardiogenic shock, a strategy of CO-PCI was associated with lower risk for short-term renal failure (OR: 0.75; 95% CI: 0.61-0.93; I2 = 0.0%), with no significant difference in MACE, all-cause mortality, re-infarction, revascularization, cardiac death, heart failure, major bleeding, or stroke compared with an immediate MV-PCI strategy. In patients complicated by CTO, a strategy of CO-PCI was associated with higher risk for long-term MACE (OR: 2.06; 95% CI: 1.39-3.06; I2 = 54.0%), all-cause mortality (OR: 2.89; 95% CI: 2.09-4.00; I2 = 0.0%), cardiac death (OR: 3.12; 95% CI: 2.05-4.75; I2 = 16.8%), heart failure (OR: 1.99; 95% CI: 1.22-3.24; I2 = 0.0%), and stroke (OR: 2.80; 95% CI: 1.04-7.53; I2 = 0.0%) compared with a staged MV-PCI strategy, without any difference in re-infarction, revascularization, or major bleeding. CONCLUSIONS: For patients with STEMI and multivessel coronary artery disease complicated by cardiogenic shock, an immediate multivessel PCI was not advocated due to a higher risk for short-term renal failure, whereas for patients complicated by CTO, a staged multivessel PCI was advocated due to reduced risks for long-term MACE, all-cause mortality, cardiac death, heart failure, and stroke.

Pramipexole attenuates neuronal injury in Parkinson's disease by targeting miR-96 to activate BNIP3-mediated mitophagy.

BACKGROUND: Parkinson's disease is a common neurodegenerative problem. Pramipexole (PPX) plays protective role in Parkinson's disease. Nevertheless, the mechanism of PPX in Parkinson's disease-like neuronal injury is largely uncertain. METHODS: 1-methyl-4-phenylpyridinium (MPP+)-stimulated neuronal cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice were used as the model of Parkinson's disease. MPP+-induced neuronal injury was assessed via cell viability, lactic dehydrogenase (LDH) release and apoptosis. microRNA-96 (miR-96) and BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) abundances were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or Western blotting. Mitophagy was tested by Western blotting and immunofluorescence staining. MPTP-induced neuronal injury in mice was investigated via behavioral tests and TUNEL. RESULTS: PPX alleviated MPP+-induced neuronal injury via increasing cell viability and decreasing LDH release and apoptosis. PPX reversed MPP+-induced miR-96 expression and inhibition of mitophagy. miR-96 overexpression or BNIP3 interference weakened the suppressive role of PPX in MPP+-induced neuronal injury. miR-96 targeted BNIP3 to inhibit PTEN-induced putative kinase 1 (PINK1)/Parkin signals-mediated mitophagy. miR-96 overexpression promoted MPP+-induced neuronal injury via decreasing BNIP3. PPX weakened MPTP-induced neuronal injury in mice via regulating miR-96/BNIP3-mediated mitophagy. CONCLUSION: PPX mitigated neuronal injury in MPP+-induced cells and MPTP-induced mice by activating BNIP3-mediated mitophagy via directly decreasing miR-96.

TiO2-supported Au-Ag plasmonic nanocatalysts achieved by plasma restructuring and activation.

Plasmonic Au-Ag/TiO2 bimetallic nanocatalyst is regarded as a promising visible-light (VL) photocatalyst due to its wide light absorption and potentially enhanced activity. For its preparation, Au precursors usually contain Cl and co-impregnation/co-deposition suffers from AgCl precipitation, and consequently Au and Ag have to be sequentially supported. However, Au and Ag species of the sequential preparation are individually isolated and difficult to be homogeneously mixed. Here we report an Au-Ag plasmonic nanocatalyst achieved by plasma restructuring and activation from the sequential preparation. The isolated cationic Au and Ag species on the sequentially-prepared Au-Ag/TiO2 sample are restructured to be homogeneously mixed and highly activated by O2 plasma, which can be partially auto-reduced to Au-Ag bimetallic nanoparticles within the induction period of a few minutes in VL photocatalytic oxidation of CO. The Au-Ag plasmonic nanocatalyst exhibits a strongly enhanced activity in the VL photocatalytic reaction. The contribution of O2 plasma treatment and the enhancement mechanism for the Au-Ag plasmonic nanocatalyst are disclosed.

Efficacy of Micro-Transplantation Consolidation Therapy for Patients with Acute Myeloid Leukemia after Complete Remission / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of micro-transplantation in acute myeloid leukemia (AML).@*METHODS@#The clinical data of 13 adult AML patients who received micro-transplantation as consolidation therapy from July 2014 to October 2019 was retrospectively analyzed, and the adverse reactions and efficacy of micro-transplantation were followed up.@*RESULTS@#Eight patients received micro-transpantation were still in complete remission, 5 patients relapsed after micro-transplantation, 1 of them received umbilical cord blood micro-transplantation after remission by reinduction, and all of the 13 patients have survived till now. The median overall survival time was 13 months, and the median relapse-free survival time was 12 months. All 13 patients developed grade 2-4 hematological adverse reactions. The median recovery time of neutrophils and platesets was 13 (11-15) and 15 (13-17) days, respectively. None of the 13 patients developed acute or chronic graft versus host disease. Twelve patients suffered from different infections, however, there were no serious organ function injury complications happened.@*CONCLUSION@#The micro-transplomtation of HLA-incompatible stem cells derived from peripheral blood or umbilical and blood is an effective regimen for the consolidation therapy of AML, especially for the patients suffered from low and moderate risk of AML or the aged AML patients.

Prognostic value of programmed cell death ligand 1 (PD-L1) for hepatocellular carcinoma: a meta-analysis.

The prognostic role of programmed death ligand-1 (PD-L1) expression in hepatocellular carcinoma (HCC) has been widely studied but the results are controversial. In this comprehensive meta-analysis, we elucidated the clinical value of PD-L1 in HCC. Relevant studies were systematically searched in the Cochrane Library, EMBASE, and PubMed until June 27, 2019. Eligible studies were validated for the prognostic effect of PD-L1 on the overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) in HCC using a hazard ratio (HR) and its 95% confidence interval (95% CI). Twenty-three studies with 3529 patients were involved in this meta-analysis. The pooled results revealed that high membrane-bound PD-L1 (mPD-L1) expression was associated with poor OS (HR: 1.42; 95% CI: 1.12-1.80; P = 0.004) and had no significant correlation with RFS (HR: 1.14; 95% CI: 0.85-1.54; P = 0.39), and DFS (HR: 1.36; 95% CI: 0.81-2.28; P = 0.25). The results also indicated that high soluble PD-L1 (sPD-L1) levels were associated with worse OS (HR: 2.93; 95% CI: 2.20-3.91; P < 0.00001). In addition, high mPD-L1 expression was associated with high alpha-fetoprotein levels (AFP; OR = 1.46; 95% CI: 1.16-1.84; P = 0.001), hepatitis (OR = 0.72; 95% CI: 0.54-0.98; P = 0.03), poor tumor differentiation (OR = 0.68; 95% CI: 0.55-0.84; P = 0.03), and tumor-infiltrating lymphocytes (OR = 3.39; 95% CI: 1.06-10.91; P = 0.04). The mPD-L1 expression had no significant correlation with age, number of tumors, gender, tumor size, liver cirrhosis, vascular invasion, tumor encapsulation, or TNM stage. The study revealed that high mPD-L1 expression in the tumor tissue and high sPD-L1 levels were associated with shorter OS in HCC. Moreover, overexpression of mPD-L1 was significantly associated with poor tumor differentiation, hepatitis, AFP elevation, and tumor-infiltrating lymphocytes.

Interfacial phenomena of water striders on water surfaces: a review from biology to biomechanics.

Water striders have intrigued researchers for centuries from the viewpoints of biology to biomechanics. In this review, we introduce the basic theories and techniques of physics and force measurement for biomechanical research into water striders. Morphological and behavioral traits of water striders are summarized and discussed from biomechanical perspectives, along with comparative study. This integrated review also highlights potential directions for studies on water-walking arthropods, which might inspire future biological and biomechanical research.

Therapeutic Response and Prognosis of Adult Acute Myeloid Leukemia with Chromosome Karyotype Abnormalities / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and prognosis of acute myeloid leukemia (AML) patients with chromosome karyotype abnormalities.@*METHODS@#The clinical features and treatment responses of 91 patients with AML were collected and analyzed retrospectively. The efficacy and survival rate of the AML patients with normal and abnormal chromosome karyotype were compared.@*RESULTS@#Chromosome translocations and monosomal karyotypes were the main heterogeneity of AML. There was no significant difference in complete remission rate and overall response rate between the normal and abnormal karyotype groups, but the recurrence rate was higher in abnormal karyotype group. There was no significant difference in response of AML patients received the standard "3+7 regimen" and pre-excitation chemotherapy in the treatment of normal and abnormal karyotype groups. The relapse free survival time (RFS) was longer in the normal karyotype group, but there was no significant difference in overall survival time (OS).@*CONCLUSION@#The abnormal karyotype of AML is an independent prognostic factor, monosomal karyotype shows a poor prognosis, and the recurrence rate in AML patients with monosomal karyotype is higher.

[Missing Data Replacement Methods in Different Scenarios].

OBJECTIVE: To compare the effect of different approaches of missing data replacement on the regression coefficient estimates r of "length of stay" on "hospital expenditure". METHODS: Data were extracted from the medical records of patients with head and neck neoplasms who were admitted to Sichuan Cancer Hospital. R 3.4.1 was used for generating and processing simulated datasets. Various scenarios were established by setting up different proportions of missing data and missing mechanisms using Monte Carlo method. Three strategies were tested for replacing missing data: Complete Case method,Expectation Maximization (EM),and Markov Chain Monte Carlo method (MCMC). The regression coefficient estimates r of standardized "length of stay" on standardized logarithmic "hospital expenditure" were calculated using these strategies and compared with that of the original complete dataset,in terms of their accuracy (magnitude of differences in r) and precision (differences in the standard error of r). RESULTS: The three replacement methods were all acceptable (within the limit rc±0.5 sc) when missing data were generated using MAR (2∶1) mechanism,or less than 30% data were simulated as missing using the MCAR and MAR (1∶2) mechanism. The EM method had the best estimation precision. CONCLUSION: Missing data replacement should consider the proportion of missing data and potential mechanisms involved.

Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer.

Pancreatic cancer is one of the deadliest cancers with very poor prognosis, and the five-year survival rate of the patients is less than 5% after diagnosis. Kallikrein-related peptidases (KLKs) belong to a serine protease family with 15 members that play important roles in cellular physiological behavior and diseases. The high expression level of KLK7 in pancreatic cancer tissues is considered to be a marker for the poor prognosis of this disease. In this work, we set out to investigate whether KLK7 could be a target for the treatment of pancreatic cancer. Short hairpin RNAs (shRNAs) were designed and constructed in lentivirus to knock down KLK7 in pancreatic cancer cell line PANC-1, and the real time cellular analysis (RTCA) was used to evaluate cell proliferation, migration and invasion abilities. Small molecules inhibiting KLK7 were discovered by computer-aided drug screening and used to inhibit PANC-1 cells. Our results confirmed that KLK7 is significantly up-regulated in pancreatic cancer tissue, and knocking down or inhibiting KLK7 efficiently inhibited the proliferation, migration and invasion of pancreatic cancer cells. This study suggested that KLK7 could be a potential chemotherapy target for treatment of pancreatic cancer, which would provide us a novel strategy for the treatment of this disease.