Publication trends and hotspots of drug resistance in colorectal cancer during 2002-2021: A bibliometric and visualized analysis.

Background: Chemotherapy, radiotherapy, targeted therapy and immunotherapy have demonstrated expected clinical efficacy, while drug resistance remains the predominant limiting factor to therapeutic failure in patients with colorectal cancer (CRC). Although there have been numerous basic and clinical studies on CRC resistance in recent years, few publications utilized the bibliometric method to evaluate this field. The objective of current study was to provide a comprehensive analysis of the current state and changing trends of drug resistance in CRC over the past 20 years. Methods: The Web of Science Core Collection (WOSCC) was utilized to extracted all studies regarding drug resistance in CRC during 2002-2021. CiteSpace and online platform of bibliometrics were used to evaluate the contributions of various countries/regions, institutions, authors and journals in this field. Moreover, the recent research hotspots and promising future trends were identified through keywords analysis by CiteSpace and VOSviewer. Results: 1451 related publications from 2002 to 2021 in total were identified and collected. The number of global publications in this field has increased annually. China and the USA occupied the top two places with respect to the number of publications, contributing more than 60% of global publications. Sun Yat-sen University and Oncotarget were the institution and journal which published the most papers, respectively. Bardelli A from Italy was the most prolific writer and had the highest H-index. Keywords burst analysis identified that "Growth factor receptor", "induced apoptosis" and "panitumumab" were the ones with higher burst strength in the early stage of this field. Analysis of keyword emergence time showed that "oxaliplatin resistance", "MicroRNA" and "epithelial mesenchymal transition (EMT)" were the keywords with later average appearing year (AAY). Conclusions: The number of publications and research interest on drug resistance in CRC have been increasing annually. The USA and China were the main driver and professor Bardelli A was the most outstanding researcher in this field. Previous studies have mainly concentrated on growth factor receptor and induced apoptosis. Oxaliplatin resistance, microRNA and EMT as recently appeared frontiers of research that should be closely tracked in the future.

Laparoscopic and endoscopic cooperative surgery for early gastric cancer: Perspective for actual practice.

Early gastric cancer (EGC) has a desirable prognosis compared with advanced gastric cancer (AGC). The surgical concept of EGC has altered from simply emphasizing radical resection to both radical resection and functional preservation. As the mainstream surgical methods for EGC, both endoscopic resection and laparoscopic resection have certain inherent limitations, while the advent of laparoscopic and endoscopic cooperative surgery (LECS) has overcome these limitations to a considerable extent. LECS not only expands the surgical indications for endoscopic resection, but greatly improves the quality of life (QOL) in EGC patients. This minireview elaborates on the research status of LECS for EGC, from the conception and development of LECS, to the tentative application of LECS in animal experiments, then to case reports and retrospective clinical studies. Finally, the challenges and prospects of LECS in the field of EGC are prospected and expounded, hoping to provide some references for relevant researchers. With the in-depth understanding of minimally invasive technology, LECS remains a promising option in the management of EGC. Carrying out more related multicenter prospective clinical researches is the top priority of promoting the development of this field in the future.

Kai-Xin-San Inhibits Tau Pathology and Neuronal Apoptosis in Aged SAMP8 Mice.

Alzheimer's disease (AD) is an age-related neurological disorder. Currently, there is no effective cure for AD due to its complexity in pathogenesis. In light of the complex pathogenesis of AD, the traditional Chinese medicine (TCM) formula Kai-Xin-San (KXS), which was used for amnesia treatment, has been proved to improve cognitive function in AD animal models. However, the active ingredients and the mechanism of KXS have not yet been clearly elucidated. In this study, network pharmacology analysis predicts that KXS yields 168 candidate compounds acting on 863 potential targets, 30 of which are associated with AD. Enrichment analysis revealed that the therapeutic mechanisms of KXS for AD are associated with the inhibition of Tau protein hyperphosphorylation, inflammation, and apoptosis. Therefore, we chose 7-month-old senescence-accelerated mouse prone 8 (SAMP8) mice as AD mouse model, which harbors the behavioral and pathological hallmarks of AD. Subsequently, the potential underlying action mechanisms of KXS on AD predicted by the network pharmacology analyses were experimentally validated in SAMP8 mice after intragastric administration of KXS for 3 months. We observed that KXS upregulated AKT phosphorylation, suppressed GSK3ß and CDK5 activation, and inhibited the TLR4/MyD88/NF-κB signaling pathway to attenuate Tau hyperphosphorylation and neuroinflammation, thus suppressing neuronal apoptosis and improving the cognitive impairment of aged SAMP8 mice. Taken together, our findings reveal a multi-component and multi-target therapeutic mechanism of KXS for attenuating the progression of AD, contributing to the future development of TCM modernization, including KXS, and broader clinical application.

Biomarkers of antibiotic resistance genes during seasonal changes in wastewater treatment systems.

To evaluate the seasonal distribution of antibiotic resistance genes (ARGs) and explore the reason for their patterns in different seasons and different systems, two wastewater treatment systems were selected and analyzed using high-throughput qPCR. Linear discriminant analysis (LDA) effect size (LEfSe) was used to discover the differential ARGs (biomarkers) and estimate the biomarkers' effect size. We found that the total absolute abundances of ARGs in inflows and excess sludge samples had no obvious seasonal fluctuations, while those in winter outflow samples decreased in comparison with the inflow samples. Eleven differentially abundant ARGs (biomarker genes, BmGs) (aadA5-02, aac-6-II, cmlA1-01, cmlA1-02, blaOXA10-02, aadA-02, tetX, aadA1, ereA, qacEΔ1-01, and blaTEM) in summer samples and 10 BmGs (tet-32, tetA-02, aacC2, vanC-03, aac-6-I1, tetE, ermB, mefA, tnpA - 07, and sul2) in winter samples were validated. According to 16S rRNA gene sequencing, the relative abundance of bacteria at the phylum level exhibited significant seasonal changes in outflow water (OW), and biomarker bacteria (BmB) were discovered at the family (or genus) level. Synechococcus and vadinCA02 are BmB in summer, and Trichococcus, Lactococcus, Pelosinus, Janthinobacterium, Nitrosomonadaceae and Sterolibacterium are BmB in winter. In addition, BmB have good correlations with BmGs in the same season, which indicates that bacterial community changes drive different distributions of ARGs during seasonal changes and that LEfSe is an acute and effective method for finding significantly different ARGs and bacteria between two or more classes. In conclusion, this study demonstrated the seasonal changes of BmGs and BmB at two wastewater treatment systems.

Organic compounds stimulate horizontal transfer of antibiotic resistance genes in mixed wastewater treatment systems.

Domestic wastewater treatment plants as a reservoir of antibiotic resistance genes (ARGs) have received much attention, but the effect of dyes on the propagation of ARGs has rarely been investigated. In this study, we investigated the differences in distributions of ARGs and microbial communities using high-throughput qPCR and 16S rRNA gene sequencing, respectively, between mixed (dyeing and domestic) wastewater and domestic sewage. The relative abundance of ARGs in inflows of mixed wastewater (IW2 and IW3) was higher than that of domestic wastewater (IW1). The relative abundance of mobile genetic elements in the inflow of textile dyeing wastewater (IDW3) was 3- to 13-fold higher than that in other samples. Moreover, in IDW3, some distinct high abundance ARGs, particularly operons encoding efflux pumps (such as acrR-01, acrB-01 and acrF), were significantly correlated with Streptococcus of the Firmicutes. To explore why the abundance of ARGs was relatively high in mixed wastewater, six representative types of organic compounds in textile dyeing wastewater were used to test the effect on plasmid-based conjugative transfer from E. coli HB101 to E. coli NK5449. These six compounds all facilitated the transfer of resistance-carrying RP4 plasmid, and the highest transfer frequency (approximately 10-5-10-3) was over 4- to 200-fold higher than that in the control group (approximately 10-6-10-5). These results illustrated that the six common residual compounds, particularly low-dose substances in IDW3, could facilitate the dissemination of ARGs in aquatic environments. More importantly, this study revealed for the first time that dyeing contaminants influenced horizontal gene transfer (HGT) of ARGs.

Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion.

UNLABELLED: Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary brain injury and the determination of the underlying mechanism of action in a mouse model of SWI that mimics the process of CED. After CED, mice received a gavage of ARC from 30 min to 14 days. Neurological severity scores (NSS) and wound closure degree were assessed after the injury. Histological analysis and immunocytochemistry were used to evaluated the extent of brain damage and neuroinflammation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect universal apoptosis. Enzyme-linked immunosorbent assays (ELISA) was used to test the inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10) and lactate dehydrogenase (LDH) content. Gene levels of inflammation (TNF-α, IL-6, and IL-10) and apoptosis (Caspase-3, Bax and Bcl-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Using these, we analyzed ARC's efficacy and mechanism of action. RESULTS: ARC treatment improved neurological function by reducing brain water content and hematoma and accelerating wound closure relative to untreated mice. ARC treatment reduced the levels of TNF-α and IL-6 and the number of allograft inflammatory factor (IBA)- and myeloperoxidase (MPO)-positive cells and increased the levels of IL-10. ARC-treated mice had fewer TUNEL+ apoptotic neurons and activated caspase-3-positive neurons surrounding the lesion than controls, indicating increased neuronal survival. CONCLUSIONS: ARC treatment confers neuroprotection of brain tissue through anti-inflammatory and anti-apoptotic effects in a mouse model of SWI. These results suggest a new strategy for promoting neuronal survival and function after CED to improve long-term patient outcome.