Rationality of the ethanol precipitation process in modern preparation production of Zishui-Qinggan decoction evaluated by integrating UPLC-QTOF-MS/MS-based chemical profiling/serum pharmacochemistry and network pharmacology.

INTRODUCTION: Zishui-Qinggan decoction (ZQD) is a classical traditional Chinese medicine formula (TCMF) for alleviating menopausal symptoms (MPS) induced by endocrine therapy in breast cancer patients. In the production of TCMF modern preparations, ethanol precipitation (EP) is a commonly but not fully verified refining process. OBJECTIVES: Chemical profiling/serum pharmacochemistry and network pharmacology approaches were integrated for exploring the rationality of the EP process in the production of ZQD modern preparations. MATERIAL AND METHODS: Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) was applied to identify the chemical profiles and absorbed components of ZQD. Network pharmacology was used to identify targets and pathways related to MPS-relieving efficacy. RESULTS: The chemicals of ZQDs without/with EP process (referred to as ZQD-W and ZQD-W-P, respectively) were qualitatively similar with 89 and 87 components identified, respectively, but their relative contents were different; 51 components were detectable in the serum of rats orally administered with ZQD-W, whereas only 19 were detected in that administered with ZQD-W-P. Key targets, such as AKT1, and pathways, such as the PI3K-Akt signalling pathway, affected by ZQD-W and ZQD-W-P were similar, while the neuroactive ligand-receptor interaction pathway among others and the MAPK signalling pathway among others were specific pathways affected by ZQD-W and ZQD-W-P, respectively. The specifically absorbed components of ZQD-W could combine its specific key targets. CONCLUSION: The EP process quantitatively altered the chemical profiles of ZQD, subsequently affected the absorbed components of ZQD, and then affected the key targets and pathways of ZQD for relieving MPS. The EP process might result in variation of the MPS-relieving efficacy of ZQD, which deserves further in vivo verification.

Data mining analysis reveals key acupoints and meridians for the treatment of chemotherapy-induced peripheral neuropathy.

OBJECTIVE: To explore effective acupoints and combinations for the treatment of chemotherapy-induced peripheral neuropathy (CIPN) METHODS: Clinical controlled trials and randomized controlled trials of acupuncture for CIPN were sourced from PubMed, Embase, Web of Science, and Chinese databases, including the Wanfang database, VIP Journals database, and China National Knowledge Infrastructure database. The quality of eligible research was evaluated based on CONSORT and STRICTA statements. The common acupoints, meridians, and acupoint combinations were determined from acupuncture prescriptions reporting positive effects and were analyzed using SPSS 23.0 and SPSS Modeler 14.1. Finally, a complex network was constructed using Cytoscape 3.8.2 to explore the core acupoints. RESULTS: The quality of 24 clinical trials was evaluated, and 20 acupuncture prescriptions that reported positive outcomes were included in subsequent data mining analysis. The most frequently used acupoints are ST36, LI11, LI4, LR3, and SP6. Meanwhile, they are also the core acupoints in acupuncture prescriptions according to the complex network with 28 nodes and 177 edges. The most commonly used meridians were the large intestine, stomach, and spleen. Acupoint combinations of LI11 and ST36, SP6 and ST36 were frequently used. CONCLUSION: Our study provides a reference for the selection of effective acupoints for CIPN treatment and a basis for the effective use of this form of traditional Chinese medicine. Furthermore, we found limitations in the design and implementation of the available clinical research, which should be minimized in future studies.

Exploring the Mechanism of Weikang Keli in Inhibiting Gastric Cancer through the MAPK Signaling Pathway: Based on Network Pharmacology and Experimental Verification.

Background: With a high incidence and limited treatments, gastric cancer (GC) seriously threatens human health worldwide. Weikang Keli (WK) is a compound prescription summed up from clinical experience. In our previous studies, WK has been proved to exert antitumor effects. However, there are no research studies to discuss and verify its mechanism as a compound. Objective: The aim of the study is to explore the potential molecular mechanism of WK in the treatment of GC with the aid of network pharmacology and verify it through experiments. Methods: Related databases were used to obtain genes and targets of WK and gastric cancer. A protein-protein interaction (PPI) network is constructed and visualized by Cytoscape 3.7.2. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to analyze core targets. The cell viability of MFC and BGC-823 cells was determined by CCK8. Immunofluorescence was used to determine autophagy of GC cells. Moreover, the effect of WK on the MAPK signaling pathway in GC cells and tumor tissues of ICR mice was detected by Western blot. Results: A total of 106 cross targets of WK and GC were obtained. According to the enrichment analysis of GO and KEGG, we target the MAPK signaling pathway to discuss the mechanism of WK on GC. Cell experiments proved that WK inhibited the viability of gastric cancer cells in a dose-dependent and time-dependent manner. Autophagosome aggregation and an increase in the expression of an autophagy marker protein LC3-II can also be observed in WK groups. Further animal experiments showed that the tumor inhibition rate of WK showed a dose-effect relationship. Moreover, the expressions of p-JNK, p-p38, and p-ERR1/2 proteins in the MAPK signaling pathway in WK Group were downregulated both in the cell and animal experiments, compared with the blank control group. Conclusion: WK showed an explicit antitumor effect on gastric cancer through the MAPK signaling pathway, and the curative effect varies in different concentrations. Besides, in model mice, the antitumor effect of high-dose WK group is close to that of platinum. This study provided a theoretical basis for the application of WK in the clinical treatment of gastric cancer.

A risk scoring system to predict the individual incidence of early-onset colorectal cancer.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is increasing at an alarming rate and further studies are needed to identify risk factors and to develop prevention strategies. METHODS: Risk factors significantly associated with EOCRC were identified using meta-analysis. An individual risk appraisal model was constructed using the Rothman-Keller model. Next, a group of random data sets was generated using the binomial distribution function method, to determine nodes of risk assessment levels and to identify low, medium, and high risk populations. RESULTS: A total of 32,843 EOCRC patients were identified in this study, and nine significant risk factors were identified using meta-analysis, including male sex, Caucasian ethnicity, sedentary lifestyle, inflammatory bowel disease, and high intake of red meat and processed meat. After simulating the risk assessment data of 10,000 subjects, scores of 0 to 0.0018, 0.0018 to 0.0036, and 0.0036 or more were respectively considered as low-, moderate-, and high-risk populations for the EOCRC population based on risk trends from the Rothman-Keller model. CONCLUSION: This model can be used for screening of young adults to predict high risk of EOCRC and will contribute to the primary prevention strategies and the reduction of risk of developing EOCRC.

A Prognostic Model Based on the Immune-Related lncRNAs in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors with a poor prognosis. At present, the pathogenesis is not completely clear. Therefore, finding reliable prognostic indicators for CRC is of important clinical significance. In this study, bioinformatics methods were used to screen the prognostic immune-related lncRNAs of CRC, and a prognostic risk scoring model based on immune-related lncRNAs signatures were constructed to provide a basis for prognostic evaluation and immunotherapy of CRC patients. METHODS: The clinical information and RNA-seq data of CRC patients were obtained from The Cancer Genome Atlas (TCGA) database. The information of immune-related lncRNA was downloaded from the immunology database and analysis portal. The differentially expressed immune-related lncRNAs (IRLs) were screened by the edgeR package of R software. The prognostic value of IRLs was studied. Based on Cox regression analysis, a prognostic index (IRLPI) based on IRLs was established, and the relationship between the risk score and the clinicopathological characteristics of CRC was analyzed to determine the effectiveness of the risk score model as an independent prognostic factor. RESULTS: A total of 240 differentially expressed IRLs were identified between normal colorectal cancer tissues and normal colorectal cancer tissues, in which 8 were significantly associated with the survival of CRC patients (P < 0.05), including LINC00461, LINC01055, ELFN1-AS1, LMO7-AS1, CYP4A22-AS1, AC079612.1, LINC01351, and MIR31HG. And most of the lncRNAs related to survival were risk factors for the prognosis of CRC. The index established based on the 7 survival-related IRLs found to be highly accurate in monitoring CRC prognosis. Besides, IRLPI was significantly correlated with a variety of pathological factors and immune cell infiltration. CONCLUSION: Eight immune-related lncRNAs closely related to the prognosis of CRC patients were identified from the TCGA database. At the same time, an independent IRLPI was constructed, which may be helpful for clinicians to assess the prognosis of patients with CRC and to formulate individualized treatment plans.

Catheter allotopia with totally implantable access port: A report of three cases and literature review.

Early detection and treatment are critical for preventing catheter allotopia in the totally implantable access ports and whenever possible, the right internal jugular vein should be selected as the first puncture point.

Bibliometric Analysis Reveals a 20-Year Research Trend for Chemotherapy-Induced Peripheral Neuropathy.

OBJECTIVE: A lot of research has focused on the field of chemotherapy-induced peripheral neuropathy (CIPN). In this study, we performed a bibliometric analysis of CIPN-related publications to identify the key research areas and trends over the last 20 years. METHODS: We searched the Web of Science core collection for publications related to CIPN that were published between January 2001 and September 2021. We then performed bibliometric analysis and visualization using Microsoft Excel 2019, VOSviewer, and the Bibliometric online analysis platform (https://bibliometric.com/). RESULTS: In total, we identified 2,188 eligible publications in the field of CIPN, with an increasing trend in the annual number of publications. The United States and Italy were dominant in the CIPN field. Supportive Care in Cancer was the most productive journal. G. Cavaletti and A.A. Argyriou published the largest number of papers. Of all institutions, the University of Milano-Bicocca, Italy, published the highest number of papers. Analysis of the co-occurrence of keywords revealed the specific characteristics relating to the four main clusters: oxaliplatin, paclitaxel, pain management, and quality of life (QOL). Newly emerging research focusses predominantly on neuroinflammatory mechanisms and non-pharmacological interventions for CIPN. CONCLUSION: This bibliometric study reviewed the evolutionary trends in CIPN research and identified current research hotspots and research trends. In addition, we identified journals, institutions, and authors, with the highest levels of impact to enhance the collaboration and learning.

Exploring the Possible Mechanism and Drug Targets of Huang-Qi-Gui-Zhi-Wu-Wu Decoction for the Treatment of Chemotherapy-Induced Peripheral Neuropathy on Network Pharmacology.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment, which may influence its successful completion. The Huang-Qi-Gui-Zhi-Wu-Wu decoction (HQGZWWD) has been widely used to treat CIPN in China although the pharmacological mechanisms involved have not been clarified. Using the network pharmacology approach, this study investigated the potential pathogenesis of CIPN and the therapeutic mechanisms exerted by the HQGZWWD herbal formula in CIPN. The targets of HQGZWWD were identified using traditional Chinese medicine (TCM) databases (TCMSP and ETCM) and prediction platforms (PharmMapper and TargetNet), and the genes of CIPN were collected by DisGeNET, GeneCards, and literature search. The common target interaction network between herbal formula and diseases was constructed by using Cytoscape. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal the mechanism and efficacy of HQGZWWD in the treatment of CIPN. A total of 153 CIPN-related genes were screened, and a protein-protein interaction (PPI) network with 96 nodes and 424 edges was constructed. Sixty-three active components were retrieved from HQGZWWD, with a herb-composite compound-target network including 748 nodes and 5448 edges. Forty-one targets belong to the above two networks. The analysis of network results and literature review shows that the main pathological processes of CIPN may be the inflammatory response and nerve injury, and HQGZWWD plays a therapeutic role in CIPN by regulating inflammatory response and repairing nerve injury, thus verifying the reliable efficacy of this herbal formula. In addition, we found two new potential therapeutic targets (CDK7 and GSTM2) warranting further investigation. This study fully illustrates that TCM has the characteristics of a multicompound, multitarget, and multipathway treatment, which is of great significance to study the curative effect of herbal formulations.

FuFangChangTai Decoction Activates Macrophages via Inducing Autophagy.

The traditional Chinese medicine decoction FuFangChangTai (FFCT) has been used in the therapy of colon cancer clinically, yielding alleviated toxicity and enhanced immunity. In our previous study, FFCT exerted its antitumor activity not only by inducing apoptosis but also by activating autophagy to eliminate tumor cells. However, its mechanism is not well understood. The purpose of this study was to investigate the relationship between macrophages activation and FFCT-induced autophagy. Results showed that FFCT could induce autophagy in colon cancer, as demonstrated by increased level of intracellular autophagy marker LC3 II in CT26.WT cells by fluorescence microscope and western blot assay. FFCT also facilitated numbers of vesicular bodies with bilayer membrane in CT26.WT cells, which were indicative of autophagosomes formation. Autophagosomes secreted by FFCT-treated CT26.WT cells can activate M1 type macrophages, accompanied with increased expression of costimulatory molecules CD86 and CD40 on the surface of RAW264.7 cells, and more inflammatory cytokines secretion, such as TNF-α, IL-6, MCP-1, and IL-1ß. mRNA expressions of M2 macrophages markers, such as IL-10, CD206, Arg-1, and FIZZ-1, were downregulated. And this process helps regulate the polarization of macrophages and promote the immune response. These findings support a mechanism of FFCT-induced autophagy and provide novel evidence demonstrating that macrophages are involved in FFCT-induced autophagy progression.

[Effect of compound Rhizoma Smilacinus granules on the expression of Bcl-2 and Bax gene in A549 cell lines of non-small cell lung cancers].

OBJECTIVE: To determine the effect of compound Rhizoma Smilacinus granules (CRSG) on the expression of Bcl-2 and Bax gene in A549 cell lines, and to explore the mechanism of CRSG on non-small cell lung cancers. METHODS: The SD rats were randomly divided into 2 groups: one was administrated with CRSG (n=15), and the other with the same dose of distilled water (n=15). The herbage-containing serum was obtained 2 hours after the 6th treatment. non-small lung cancer A549 cell lines were randomly divided into CRSG group, diamminedichloroplatinum (DDP) group and normal control group, which were cultivated with 10% herbage-containing serum, DDP (3g/mL), and 10% SD rats serum respectively. The cultivated cells were collected after 48 hours, and then RT-PCR technique was used to determine the expression of Bcl-2 and Bax mRNA. RESULTS: Compared with the normal control group after 48 h, the level of Bcl-2 mRNA and the rate of Bc-2/Bax decreased in the CRSG group and the DDP group, and the level of Bax mRNA increased with significant difference (P<0.01). CONCLUSION: non-small cell lung cancer A549 cell lines have a high level of Bcl-2 mRNA and a low level of Bax mRNA. CRSG can significantly down-regulate the expression of Bcl-2 mRNA and the rate of Bc-2/Bax, and obviously up-regulate the expression of Bax mRNA, which probably is one of the molecular mechanisms of CRSG in inhibiting the growth of non-small cell lung cancers.