Anti-tumor pharmacology of natural products targeting mitosis

Cancer has been an insurmountable problem in the history of medical science. The uncontrollable proliferation of cancer cells is one of cancer’s main characteristics, which is closely associated with abnormal mitosis. Targeting mitosis is an effective method for cancer treatment. This review summarizes several natural products with anti-tumor effects related to mitosis, focusing on targeting microtubulin, inducing DNA damage, and modulating mitosis-associated kinases. Furthermore, the main disadvantages of several typical compounds, including drug resistance, toxicity to non-tumor tissues, and poor aqueous solubility and pharmacokinetic properties, are also discussed, together with strategies to address them. Improved understanding of cancer cell mitosis and natural products may pave the way to drug development for the treatment of cancer.     

Characterizing the Phase-Structure and Rheological Response-Behavior of Multi-Walled Carbon Nanotubes Modified Asphalt-Binder

In this study, the phase-structure and rheological response-behavior of multi-walled carbon nanotube (MWCNTs) modified asphalt-binder (MWCNTs-MA) were measured and quantified in the laboratory. The changes in the molecular dynamics due to MWCNTs modification were simulated and quantified based on the intermolecular interaction energy computations, electrostatic potential surface analyses and phase-structure modeling of the asphalt-binder matrix. The rheological properties such as the asphalt-binder viscosity and complex modulus, of both the base and modified asphalt-binders, were determined using the standard Brookfield viscometer (BV) and dynamic shear rheology (DSR) test devices, respectively. In comparison to the base asphalt-binder, the corresponding BV-DSR test results exhibited higher viscosity and complex modulus for the MWCNTs modified asphalt-binder, with reduced sensitivity and susceptibility to temperature variations. From the study results, it was observed that MWCNTs significantly improved the rheological properties and high-temperature performance of the asphalt-binder. Overall, the study has demonstrated that MWCNT modified asphalt-binder has great promising potential for application and usage as a road-pavement material, particularly with respect to mitigating the high temperature related distresses such as rutting.     

The role of toll-like receptors (TLRs) in pan-cancer

BackgroundToll-like receptors (TLRs) are important components of the innate and adaptive immune systems, and abnormal TLR expression has been linked to a variety of cancers. However, there was a lack of clarity on the association of TLR stimulation with the carcinogenesis of cancer. The study''s goal was to analyse the clinical importance of TLRs expression at the mRNA level in pan-cancer datasets, as well as the link between TLR expression and carcinogenesis, progression, and clinical prognosis.MethodsThe expression profile of TLRs derived from UCSC pan-cancer data was analysed in multiple dimensions, including clinical analysis, immunological subtype analysis, tumour microenvironment (TME) analysis, tumour stem cell correlation analysis, and drug sensitivity analysis. Additionally, we analyse protein-protein interactions, functional enrichment, and chromatin accessibility, as well as TLR expression in single-cell sequencing data.ResultsOur multi-omics analysis results imply that TLRs may operate as a biological marker for carcinogenesis and progression, a potential target for anti-tumour therapy, and a prognostic biomarker, laying the theoretical groundwork for future translational medicine research.ConclusionTLRs are involved in the formation of malignancies and can be explored in further detail as potential prognostic indicators.

Key Messages

• Toll-like receptors (TLRs) are key factors in the process of the innate and adaptive immune response, and their aberrant expression of TLRs have been widely reported in various cancer. However, the association between TLRs stimulation and tumorigenesis of cancer has not been well clarified.
• In this study, in the pan-cancer data, integrated TLR family gene expression analysis, clinical correlation analysis, immune subtype correlation analysis, tumour microenvironment correlation analysis, tumour stem cell correlation analysis, and drug sensitivity correlation analysis were performed.
• TLRs play an important role in the development of tumours and can be studied in depth as potential prognostic markers.

     

小脑发育不良性节细胞瘤与Cowden综合征:6例临床分析

目的分析小脑发育不良性节细胞瘤（LDD）的临床、影像学和病理学特征,探讨LDD与Cowden综合征（CS）之间的关系。方法回顾6例LDD患者的临床、影像学和病理学资料,根据国际CS协会（ICC）标准体检,并与1例CS患者比较。结果患者发病年龄23-56岁,平均39岁,常见症状为颅内压增高、小脑征及颅神经麻痹表现。CT示后颅等密度和低密度占位,部分钙化,MRI表现为特征性的“虎纹征”;病理特征为小脑层状结构紊乱,颗粒细胞和浦肯野细胞减少,而异常神经节细胞增多。患者术后预后多良好。随访到的5例LDD患者中3例（60％）符合CS诊断标准,1例CS患者未合并LDD。结论LDD为小脑的少见良性病变,MRI为最佳影像学诊断手段,全切手术为首选治疗方法。LDD可能为CS在中枢神经系统的表现。     

Effects of cluster nursing on cardiac function and quality of life in coronary heart disease patients with chronic heart failure: A protocol of randomized controlled trial

Background:Coronary heart disease (CHD) chronic heart failure has high morbidity and mortality, which poses a serious threat to patients’ quality of life and life safety. For the treatment of chronic heart failure of CHD, in addition to drugs, high quality nursing measures are also very important. Cluster nursing is a high-quality nursing model based on evidence-based evidence. There is no clinical study to evaluate the effect of cluster nursing on cardiac function and quality of life of CHD patients with chronic heart failure.Methods:This is a prospective randomized controlled trial to investigate the effects of cluster nursing on cardiac function and quality of life in patients with CHD chronic heart failure. Approved by the Clinical Research Ethics Committee of our hospital, patients will be randomly assigned to either routine nursing or cluster nursing. They will be followed up for 3 months after 4 weeks of treatment. Observation indicators include: The total effective rate of cardiac function improvement, Minnesota Living with Heart Failure Questionnaire, left ventricular ejection fraction, N-terminal pro-brain natriuretic peptide, 6-minute walk test, adverse reaction, etc. Data were analyzed using the statistical software package SPSS version 25.0.Discussion:This study will evaluate the effects of cluster nursing on cardiac function and quality of life of CHD patients with chronic heart failure. The results of this study will provide clinical basis for establishing reasonable and effective nursing programs for CHD patients with chronic heart failure.     

个案护理管理模式在预防及护理老年吸入性肺炎的应用分析

目的 探讨个案护理管理模式在老年吸入性肺炎高危患者中的应用效果。方法 选取2021年1月至10月抚州市第一人民医院收治的120例老年吸入性肺炎高危患者作为研究对象,采用随机数字表法将其分为观察组（60例）和对照组（60例）。观察组患者采用个案护理管理模式,对照组患者采用常规护理。比较两组患者的住院天数、体温、广泛性焦虑量表（GAD-7）评分、外周血白细胞计数、肺炎发生率及护理总满意度。结果 观察组患者的住院天数短于对照组,体温、肺炎发生率均低于对照组,差异有统计学意义（P<0.05）。干预后,两组患者的GAD-7评分、外周血白细胞计数均低于干预前,且观察组的GAD-7评分、外周血白细胞计数低于对照组,差异有统计学意义（P<0.05）。观察组患者的护理总满意度高于对照组,差异有统计学意义（P<0.05）。结论 个案护理管理模式有助于降低老年吸入性肺炎高危患者的肺炎发生率,调节其外周血白细胞计数水平与体温水平,缩短住院天数,并可对其心理状态、护理总满意度产生良性影响。     

Development and Primary Application of an Indirect ELISA Based on Rep Protein to Analyze Antibodies against Porcine Cocirvirus-like Virus (PCLV)

Porcine circovirus-like virus (PCLV) is a member of circovirus that contains a single-strand DNA genome, which may be one of the pathogens that causes diarrheal symptoms in pigs. The Rep protein encoded by the genome of PCLV may be responsible for viral genome replication. The development of serological detection methods for PCLV is of great necessity for clinical diagnosis, as well as epidemiological investigations. Therefore, this study attempted to build an indirect enzyme-linked immunosorbent assay (ELISA) to examine antibodies against PCLV based on the His-tagged recombinant Rep protein. Full-length PCLV Rep protein was induced and expressed in E. coli and was purified as an antigen to establish an ELISA detection kit. The purified Rep protein was used to inject into mice to produce specific antibodies. There was no cross-reaction of Rep-based ELISA with antisera against other porcine viruses. The intra-assay and inter-assay coefficient variations (CVs) were 0.644–8.211% and 0.859–7.246%, respectively, indicating good repeatability. The non-cross-reaction with TGEV, PRRSV and PCV2 testing showed high sensitivity and high specificity for this ELISA assay. A total of 1593 serum samples collected from different pig farms in Jiangxi Province were tested for anti-PCLV Rep antibodies, and 284 (17.83%) of the 1593 samples were Rep antibody positive. Altogether, the indirect ELISA detection tool developed in this study could be applied to examine serum of PCLV antibodies with good repeatability, high sensitivity and high specificity. In addition, field sample detection results suggested that the PCLV antibody has a low prevalence in pig populations in Jiangxi Province of China.     

High-Dose Dual Therapy Versus Bismuth-Containing Quadruple Therapy for the Treatment of Helicobacter pylori Infection: A Systematic Review with Meta-Analysis

Background:This study aimed to evaluate the efficacy and safety of high-dose dual therapy for Helicobacter pylori (H. pylori) eradication compared to bismuth-containing quadruple therapy.Methods:The electronic database of PubMed, Embase, and Cochrane Library were searched from inception to March 18, 2021. Randomized, controlled trials that evaluated high-dose dual therapy versus bismuth-containing quadruple therapy for H. pylori infection were included.Results:We included 6 studies containing 1677 patients with H. pylori infection. This meta-analysis demonstrated that high-dose dual therapy achieved similar eradication rate compared with bismuth-containing quadruple therapy (intention-to-treat: 84.6% vs 83.7%, relative risk (RR) = 1.01, 95% CI: 0.97-1.06, P = .49; per-protocol = 88.4% vs 89.0%, RR = 1.00, 95% CI: 0.97-1.04, P = .99). However, high-dose dual therapy showed fewer side effects (13.1% vs 32.0%, RR = 0.51, 95% CI: 0.34-0.78, P = .002) and better compliance (96.1% vs 93.3%, RR = 1.03, 95% CI: 1.00-1.05, P = .03) compared to bismuth-containing quadruple therapy.Conclusion:This meta-analysis demonstrated that high-dose dual therapy is equally effective with bismuth-containing quadruple therapy in eradicating H. pylori, with fewer side effects and better compliance.     

Isoproterenol disperses distribution of NADPH oxidase,MMP-9, and pPKCε in the heart,which are mitigated by endothelin receptor antagonist CPU0213

Aim： Spatial dispersion of bioactive substances in the myocardium could serve as pathological basis for arrhythmogenesis and cardiac impairment by β-adrenoceptor stimulation. We hypothesized that dispersed NADPH oxidase, protein kinase Cε （PKCε）, early response gene （ERG）, and matrix metalloproteinase 9 （MMP-9） across the heart by isoproterenol （ISO） medication might be mediated by the endothelin （ET） - ROS pathway. We aimed to verify if ISO induced spatially heterogeneous distribution of pPKCε, NAPDH oxidase, MMP-9 and ERG could be mitigated by either an ET receptor antagonist CPU0213 or iNOS inhibitor aminoguanidine. Methods：Rats were treated with ISO （1 mg/kg sc） for 10 days, and drug interventions （mg/kg） either CPU0213 （30 sc） or aminoguanidine （100 ip） were administered on days 8-10. Expression of NADPH oxidase, MMP-9, ERG, and PKCε in the left and right ventricle （LV, RV） and septum （S） were measured separately. Results： Ventricular hypertrophy was found in the LV, S, and RV, in association with dispersed QTc and oxidative stress in ISO-treated rats. mRNA and protein expression of MMP-9, PKCε, NADPH oxidase and ERG in the LV, S, and RV were obviously dispersed, with augmented expression mainly in the LV and S. Dispersed parameters were re-harmonized by either CPU0213, or aminoguanidine. Conclusion： We found at the first time that ISO-induced dispersed distribution of pPKCε, NADPH oxidase, MMP-9, and ERG in the LV, S, and RV of the heart, which were suppressed by either CPU0213 or aminoguanidine. It indicates that the ET-ROS pathway plays a role in the dispersed distribution of bioactive substances following sustained β-receptor stimulation.