Advancement of chimeric antigen receptor-natural killer cells targeting hepatocellular carcinoma

With the advance of genome engineering technology, chimeric antigen receptors (CARs)-based immunotherapy has become an emerging therapeutic strategy for tumors. Although initially designed for T cells in tumor immunotherapy, CARs have been exploited to modify the function of natural killer (NK) cells against a variety of tumors, including hepatocellular carcinoma (HCC). CAR-NK cells have the potential to sufficiently kill tumor antigen-expressing HCC cells, independent of major histocompatibility complex matching or prior priming. In this review, we summarize the recent advances in genetic engineering of CAR-NK cells against HCC and discuss the current challenges and prospects of CAR-NK cells as a revolutionary cellular immunotherapy against HCC.     

射频电流致心率变异性改变的机理探讨

采用心率功率谱对11例房室结折返性心动过速（A组）、9例右侧旁边（B组）和21例左侧旁道（C组）致房室折返性心动过速的患者于射频消融前、消融后1、2、3、5、10d进行连续动态观察，比较低频段功率（LFP）、高频段功率（HFP）和LFP与HFP的比值。结果显示所有患者于术后1dHFP均降低，但A组持续下降时间长于B、C两组，消融能量小于3500J者，LFP于术后第2天才下降，消融能量大于3500J者手术后第1天即出现下降，结果同时显示上述心率变异性（HRV）的改变于术后10d可恢复至术前水平。表明消融后HRV的降低系副交感神经受损的结果，而消融能量大者亦可同时损伤交感神经，导管的机械刺激和电刺激对HRV无影响。     

计算机辅助导航全膝关节置换术的当前概念和进展

全膝关节置换术(TKR)旨在重建胫股和髌股关节的稳定性,缓解疼痛,改善患者生活质量.计算机辅助导航系统的应用能够有效减少常规TKR手术下肢力线重建中的人为错误并改善手术结果.现有证据表明,应用计算机辅助导航系统能够显著减少术后机械轴和冠状位假体位置的异常值.此外,导航系统提供了常规手术无法获得的软组织平衡客观评估.应用...     

A case report of tumor lysis syndrome after stage-one ALPPS

Rationale:Tumor lysis syndrome is a potentially lethal condition caused by rapid cell death, releasing a high level of toxic cytokines. It is common in patients with hematological malignancy but rare in solid tumors.Patient concerns:A 64-year-old patient presented to our unit with a 17.3-cm hepatocellular carcinoma and marginal liver reserve. The first-stage operation of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was performed.Diagnosis:The patient was found to be anuric with grossly deranged electrolytes after the first-stage operation. Tumor lysis syndrome was diagnosed.Interventions:The patient was transferred to the intensive care unit for aggressive fluid administration and continuous venovenous hemofiltration for the management of tumor lysis syndrome.Outcomes:The patient recovered and then underwent the second-stage operation of ALPPS with extended right hepatectomy 8 days after the initial operation without any long-term sequelae.Lessons:ALPPS is a relatively new technique in liver surgery, entailing an increased risk of tumor lysis syndrome due to an in situ tumor after the first-stage operation. Clinicians should have a high index of suspicion regarding this potentially lethal complication with prompt management.     

Mineralocorticoid receptor antagonist-mediated cognitive improvement in a mouse model of Alzheimer's type: possible involvement of BDNF-H2S-Nrf2 signaling

The present study explored the role and mechanisms of mineralocorticoid receptor antagonists in β-amyloid (Aβ)-induced cognitive impairment. A single intracerebroventricular injection of Aβ_1-42 was given to mice, and after 14 days of injection, memory was evaluated using the Morris water maze test. Spironolactone (25 and 50 mg/kg) and eplerenone (50 and 100 mg/kg) were administered for two days before and for 14 days after Aβ injection. Mineralocorticoid receptor blockers attenuated Aβ-induced cognitive impairment assessed in terms of decrease in day 4 escape latency time (ELT) in comparison to day 1 ELT (suggesting an increase in learning) along with an increase in time spent in target quadrant on day 5 (suggesting the retrieval of learned things). These drugs also increased the expression of BDNF, H₂S, Nrf2, reduced glutathione, and decreased β-amyloid and TNF-α in the frontal cortex and hippocampus. Co-administration of ANA-12, BDNF receptor antagonist (0.25 and 0.5 mg/kg) abolished cognitive improving functions of mineralocorticoid receptor blockers, attenuated H₂S, Nrf2, reduced glutathione, and decreased β-amyloid and TNF-α. It is concluded that spironolactone and eplerenone attenuate cognitive decline of Alzheimer's type, possibly through upregulation of BDNF levels in the frontal cortex and hippocampus, which may increase H₂S, decrease Aβ, activate Nrf2-dependent antioxidant system, and decrease neuroinflammation.     

大蒜多糖预处理对缺氧缺糖/复氧复糖大鼠心肌细胞的拮抗作用

目的:研究大蒜多糖(GP)预处理对缺氧缺糖/复氧复糖损伤大鼠心肌细胞的拮抗作用研究,并初步探讨其作用机制。方法:采用连二亚硫酸钠(Na2S2O4)建立乳鼠心肌细胞糖氧剥离的A/R损伤模型,不同剂量GP(10、30和100mg/L)预处理24h后,比色法测定细胞培养液中iNOS和NO含量,测定细胞内SOD活性及MDA含量。结果:与A/R模型组比较,GP预处理可增加胞内SOD活性和培养液中iNOS活力,降低NO释放量和胞内MDA含量。结论:GP预处理对A/R损伤心肌细胞具有明显的抗氧化作用,可能与清除自由基的产生有关。     

Isolation,Characterization, and Genome Analysis of a Novel Bacteriophage,Escherichia Phage vB_EcoM-4HA13, Representing a New Phage Genus in the Novel Phage Family Chaseviridae

Shiga toxin-producing Escherichia coli (STEC) is one of the leading causes of foodborne illnesses in North America and can lead to severe symptoms, with increased fatality risk for young children. While E. coli O157:H7 remains the dominant STEC serotype associated with foodborne outbreaks, there has been an increasing number of non-O157 STEC outbreaks in recent years. For the food industry, lytic bacteriophages offer an organic, self-limiting alternative to pathogen reduction—one that could replace or reduce the use of chemical and physical food processing methods. From EHEC-enriched sewage, we isolated a novel bacteriophage, vB_EcoM-4HA13 (4HA13). Phenotypic characterizations revealed 4HA13 to possess a myoviral morphotype, with a high specificity to non-motile O111 serotype, and a long latent period (90 min). Through genomic analyses, this 52,401-bp dsDNA phage was found to contain 81 CDS, but no detectable presence of antibiotic resistance, integrase, or virulence genes. A BLASTn search for each of the identified 81 CDS yielded homologues with low levels of similarity. Comparison of RNA polymerase and terminase large subunit amino acid sequences led to the proposal and acceptance of a new bacteriophage family, Chaseviridae, with 4HA13 representing a new species and genus. The discovery of this phage has broadened our current knowledge of bacteriophage diversity.     

Grafting antibiofilm polymer hydrogel film onto catheter by SARA SI-ATRP

Abstract

Catheters are widely used and play an important role in medicine. However, catheter-associated infection is prevalent even under stringent sterile conditions. Biofilms are formed when bacteria populate the surfaces of catheters. This makes the biofilm resistant to antibiotics. Hence, it is imperative for there to be an inherently antifouling and anti-bacterial catheter to mitigate the formation of biofilm. This paper aims to outline the synthesis of non-leachable anti-biofilm and anti-bacterial cationic film coatings through direct polymerization using supplemental activator and reducing agent surface initiated atom transfer radical polymerization (SARA SI-ATRP). Three crosslinked cationic coatings comprising of Diallyl dimethyl ammonium chloride (DADMAC), or ε-poly-L-lysine HCl methacrylic acid (EPL-MA) together with a crosslinker (polyethylene glycol dimethacrylate, PEGDMA) were investigated. These non-leachable covalently linked coatings with DADMAC can achieve more than 2 log reduction (99.0%) with Methicillin-resistant Staphylococcus aureus (MRSA) and 1.25 log reduction (94.4%) with Vancomycin resistant Enterococcus (VRE) in in vitro studies.     

Sequences and replication of genomes of the archaeal rudiviruses SIRV1 and SIRV2: relationships to the archaeal lipothrixvirus SIFV and some eukaryal viruses

The double-stranded DNA genomes of the viruses SIRV1 and SIRV2, which infect the extremely thermophilic archaeon Sulfolobus and belong to the family Rudiviridae, were sequenced. They are linear, covalently closed at the ends, and 32,312 and 35,502 bp long, respectively, with an A+T content of 75%. The genomes of SIRV1 and SIRV2 carry inverted terminal repeats of 2029 and 1628 bp, respectively, which contain multiple direct repeats. SIRV1 and SIRV2 genomes contain 45 and 54 ORFs, respectively, of which 44 are homologous to one another. Their predicted functions include a DNA polymerase, a Holliday junction resolvase, and a dUTPase. The genomes consist of blocks with well-conserved sequences separated by nonconserved sequences. Recombination, gene duplication, horizontal gene transfer, and substitution of viral genes by homologous host genes have contributed to their evolution. The finding of head-to-head and tail-to-tail linked replicative intermediates suggests that the linear genomes replicate by the same mechanism as the similarly organized linear genomes of the eukaryal poxviruses, African swine fever virus and Chlorella viruses. SIRV1 and SIRV2 both contain motifs that resemble the binding sites for Holliday junction resolvases of eukaryal viruses and may use common mechanisms for resolution of replicative intermediates. The results suggest a common origin of the replication machineries of the archaeal rudiviruses and the above-mentioned eukaryal viruses. About 1/3 of the ORFs of each rudivirus have homologs in the Sulfolobus virus SIFV of the family Lipothrixviridae, indicating that the two viral families form a superfamily. The finding of inverted repeats of at least 0.8 kb at the termini of the linear genome of SIFV supports this inference.