Effect of Preoperative immune-enhancing Enteral Nutrition on the Outcomes of Laparoscopic Surgery for Colon Cancer in elderly Patients: A Randomized Controlled Trial.

Objective: This study aims to explore the impact of immune-enhanced enteral nutrition on postoperative outcomes, focusing on inflammatory response, intestinal mucosal barrier integrity, and immune function following laparoscopic colon cancer surgery in elderly patients. Methods: In this single-center, randomized controlled trial, ninety-six elderly patients undergoing laparoscopic resection of colon tumors were enrolled and equally divided into two groups by random allocation. The control group (n=48) received standard enteral nutrition, while the experimental group (n=46) was administered immune-enhancing enteral nutrition. We assessed and compared specific metrics such as nutritional status (e.g., albumin levels), cellular immune status (CD4+ and CD8+ T-cell counts), inflammatory markers (e.g., C-reactive protein), and indicators of intestinal mucosal barrier function (e.g., D-lactate levels) before and after the intervention in both groups. Results: Initial comparison of baseline characteristics between the two groups showed no significant differences (P > .05). Postoperatively, the experimental group demonstrated significantly lower levels of inflammatory markers and an improved ratio of CD4+/CD8+ T-cells compared to the control group at day 7 (P < .05). Furthermore, nutritional status and markers indicative of intestinal mucosal barrier integrity were notably better in the experimental group at this time point. Conclusion: Immune-enhanced enteral nutrition is effective in enhancing intestinal mucosal barrier function, boosting immune response, and improving nutritional status in elderly patients post-laparoscopic colon cancer surgery. It also contributes to mitigating the inflammatory response, proving its safety and tolerability for clinical use.

Multi-omics reveals that 5-O-methylvisammioside prevention acute liver injury in mice by regulating the TNF/MAPK/NF-κB/arachidonic acid pathway.

BACKGROUND: The pathogenesis of acute liver injury (ALI) has been a pressing issue in the medical scientific community. We previously found that 5-O-methylvisammioside (MeV) from Saposhnikovia divaricata (Turcz.) Schischk has excellent anti-inflammatory properties. However, the mechanism by which MeV protects against ALI still needs to be deeply investigated. PURPOSE: In the present study, we established an acetaminophen (APAP) -induced ALI mouse model and pre-protected the mice with MeV. METHODS & RESULTS: Our findings indicate that MeV (5 and 10 mg/kg) lowered the blood levels of alanine aminotransferase and aspartate aminotransferase and reduced the infiltration of inflammatory cells in the liver. MeV initially showed an inhibitory effect on ALI. We then analyzed the molecular mechanisms underlying the effects of MeV by transcriptomic and metabolomic analyzes. Through transcriptomic analysis, we identified 4675 differentially expressed genes between the APAP+MeV group and the APAP-induced ALI group, which were mainly enriched in the MAPK pathway, the TNF pathway, and the NF-κB pathway. Through metabolomic analysis, we found that 249 metabolites in the liver were differentially regulated between the APAP+MeV group and the APAP- induced ALI group, which were mainly enriched in the arachidonic acid pathway. The mRNA expression levels of key genes (encoding TNF-α, p38, AP-1, RelB, IL-1ß, and Ptges), as determined by RT-PCR analysis, were consistent with the RNA-seq data. The ELISA results indicate that MeV markedly decreased the serum levels of TNF-α and IL-1ß in mice. Finally, the key proteins in the NF-κB and MAPK pathways were examined using immunoblotting. The results showed that MeV decreased IκB-α phosphorylation and inhibited the nuclear translocation of NF-κB. In addition, MeV reduced the hepatic inflammatory burst mainly by inhibiting the phosphorylation of p38 and JNK in the MAPK pathway. CONCLUSION: The present study demonstrated (i) that MeV could ameliorate APAP-induced ALI by inhibiting arachidonic acid metabolism and the TNF, MAPK, and NF-κB pathways, and (ii) that MeV is a promising drug candidate for the prevention of ALI.

Effects of acupuncture on mental health of migraine patients: a systematic review and meta-analysis.

BACKGROUND: Migraine is a neurological disease characterized by moderate to severe headache and various neurological symptoms. It is often cause mood and anxiety disorders that can seriously affect quality of life. Acupuncture has been claimed to have a role in treating neuropsychiatric disorders and is becoming increasingly popular. However, it remains unclear whether current evidence is sufficient to support acupuncture in improving mental health in migraine patients. OBJECTIVES: This systematic review and meta-analysis aimed to investigate the effect of acupuncture on the management of pain and mood disorders in patients with migraine. METHODS: We searched PubMed, Cochrane Library, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI) and Wan Fang Data Knowledge Service Platform for reports, conferences and academic papers published before January 1, 2022. Randomized controlled trials (RCTs) including acupuncture, sham acupuncture and medication for migraine were included. Stata 16.0 software and Cochrane RoB2.0 were used for data processing and migration risk analysis. RESULT: Thirteen randomized controlled trials containing 1766 migraine patients were included in the present study, the results showed that compared with sham acupuncture and medication, acupuncture seemed to have advantage in improving SAS (WMD: -5.64;95% CI: -10.89, -0.39; p = 0.035) and SDS (WMD: -4.65; 95% CI: -9.25, -0.05; p = 0.048) in migraine patients. And it seems to be more effective in improving MH (SMD: 0.77; 95% CI: 0.19, 1.35; p = 0.009), VAS (SMD: -1.06; 95% CI: -1.73, -0.4; p = 0.002;) and MSQ (WMD: 4.76; 95% CI: 2.36, 7.15; p < 0.001) than sham acupuncture and medication. CONCLUSION: The present results suggest that, compared with Western medicine and sham acupuncture, acupuncture seems to be able to effectively improve anxiety and depression in migraine patients.And it may be more effective in improving SF36-mental health, VAS and MSQ than shame acupuncture or Western medicine. The results of this study need to be verified by higher quality RCTs.

Research trends in complementary and alternative treatments for insomnia over the past decade: A bibliometrics analysis.

Insomnia is the most common sleep disorder, with persistent insomnia being associated with greater risk and leading to a range of functional consequences that place a heavy burden on patients and healthcare systems. A weight of evidence has shown that complementary and alternative medicine (CAM) seems to have a positive effect on improving sleep. However, the research trends of CAM intervention for insomnia have not been studied systematically through bibliometrics. We searched the relevant literature over the past decade in the Web of Science Core Collection database on September 20, 2022 and used CiteSpace and gCLUTO to visually analyze and cluster countries, institutions, authors, journals and keywords. Through screening, 1655 papers were included. In the past decade, the number of articles published in this field shown an annual trend of growth, with explosive growth in 2020. The USA has the largest number of publications, the University of Hong Kong is the leading institution in this field, and the most cited journal is Sleep. Mental condition and quality of life in patients with insomnia, insomnia related to cancer, effect of mindfulness meditation, yoga and aromatherapy on insomnia and the psychiatric symptoms resulting from the COVID-19 pandemic are at the forefront of this field. In this study, bibliometrics and visualization analysis were performed on related studies on CAM intervention for insomnia. This will be the focus and development direction of insomnia treatment in the future to formulate structured treatment plans for traditional Chinese medicine-related CAM, validate large-scale clinical trials, solve cancer comorbidity insomnia and related psychiatric symptoms and deal with mental health-related insomnia after public health outbreaks.

Ginsenosides Rg1 and CK Control Temozolomide Resistance in Glioblastoma Cells by Modulating Cholesterol Efflux and Lipid Raft Distribution.

Background: Cholesterol efflux and lipid raft redistribution contribute to attenuating temozolomide resistance of glioblastoma. Ginsenosides are demonstrated to modify cholesterol metabolism and lipid raft distribution, and the brain distribution and central nervous effects of whose isoforms Rb1, Rg1, Rg3, and CK have been identified. This study aimed to reveal the role of Rb1, Rg1, Rg3, and CK in the drug resistance of glioblastoma. Methods: The effects of ginsenosides on cholesterol metabolism in temozolomide-resistant U251 glioblastoma cells were evaluated by cholesterol content and efflux assay, confocal laser, qRT-PCR, and Western blot. The roles of cholesterol and ginsenosides in temozolomide resistance were studied by CCK-8, flow cytometry, and Western blot, and the mechanism of ginsenosides attenuating resistance was confirmed by inhibitors. Results: Cholesterol protected the survival of resistant U251 cells from temozolomide stress and upregulated multidrug resistance protein (MDR)1, which localizes in lipid rafts. Resistant cells tended to store cholesterol intracellularly, with limited cholesterol efflux and LXRα expression to maintain the distribution of lipid rafts. Ginsenosides Rb1, Rg1, Rg3, and CK reduced intracellular cholesterol and promoted cholesterol efflux in resistant cells, causing lipid rafts to accumulate in specific regions of the membrane. Rg1 and CK also upregulated LXRα expression and increased the cytotoxicity of temozolomide in the presence of cholesterol. We further found that cholesterol efflux induction, lipid raft redistribution, and temozolomide sensitization by Rg1 and CK were induced by stimulating LXRα. Conclusions: Ginsenosides Rg1 and CK controlled temozolomide resistance in glioblastoma cells by regulating cholesterol metabolism, which are potential synergists for temozolomide therapy.

A radical photochromic metal-organic framework for boosting NIR-II photothermal conversion and therapy.

This work demonstrates for the first time that a photochromic metal organic framework (pMOF) can be employed as a promising class of NIR-II photothermal material based on the photoinduced donor-acceptor intermolecular charge transfer process. After further surface-modification, such UV-activated pMOF-a nanoparticles allow the strong inhibition of 4T1 cancer cells under 1064 nm laser irradiation.

Acupuncture for Post-Stroke Cognitive Impairment: An Overview of Systematic Reviews.

Background: Post-stroke cognitive impairment (PSCI) is one of the most common complications after stroke. In recent years, as a complementary alternative therapy, many systematic reviews (SRs) and meta-analysis (MAs) have reported the efficacy and safety of acupuncture in improving cognitive function in patients with PSCI, but the quality of evidence is unknown and therefore needs to be evaluated comprehensively. Aim: We aimed to evaluate the SRs of acupuncture for patients with PSCI, to summarize the evidence quality of SRs to provide scientific evidence. Methods: We searched for relevant SRs and MAs in seven databases up to March 22, 2022. Two reviewers independently completed literature retrieval, screening, and data extraction. We used A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) to evaluate the methodological quality; the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool to determine the strength of evidence; and the ROBIS tool to assess RoB. Results: We identified 14 SRs. The methodological quality of all SRs was low (2/14) or very low (12/14). GRADE results showed 13 were moderate quality (26%), 5 were low quality (10%), and 32 were very-low quality (64%). RoB showed that one SR had a low risk and 13 had a high risk. Moderate quality results showed that combined acupuncture therapy was superior to western medicine or cognitive rehabilitation training in improving cognitive function, the total response rate, and the daily living ability of patients with PSCI. Conclusion: Based on the evidence, acupuncture appears to be effective and safe in improving cognitive function for patients with PSCI, but the overall quality of SRs is not high. High-quality randomized controlled trials are needed to confirm the effectiveness and safety of acupuncture on the cognitive function of patients with PSCI. Systematic Review Registration: PROSPERO CRD42022315441.

Chinese herbal medicine xuebijing injection for acute pancreatitis: An overview of systematic reviews.

Background: At present, a number of systematic reviews (SRs) on Xuebijing injection (a patent in China) in the treatment of acute pancreatitis (AP) or severe acute pancreatitis (SAP) have been published. However, the quality of evidence is uneven and has not been comprehensively evaluated. Aim: We evaluated the efficacy of Xuebijing injection for AP/SAP through an overview of SR, and to provide a scientific basis for its effectiveness and safety. Methods: We searched Cochrane Library, Embase, PubMed, SinoMed, CNKI, Wanfang, and VIP comprehensively. The retrieval period from inception to 30 November 2021, and the two reviewers independently complete the literature retrieval, data extraction and evaluation. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) and the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) were used to evaluate the methodological quality and reporting quality of the SRs, respectively. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to evaluate the quality grading of outcomes and the risk of bias in SRs was evaluated by ROBIS Tool. Finally, the RCTs involved in SRs were synthesized. Stata15.1 was used for quantitative analysis of total effectiveness rate, time until relief of abdominal pain, time until relief of abdominal distension, and serum amylase level. Results: Nine eligible SRs were included, including 92 RCTs and 6,837 participants. The quality of SRs was relatively good, and the manuscript structures were relatively complete. However, the methodological quality of SRs was low or critically low. RoB rated 5 SRs as low risk of bias and 4 SRs as high risk of bias. In GRADE, a total of 47 results were included in the 9 SRs, of which 5 results (10.64%) were moderate quality, 22 results (46.81%) were low quality, and 20 results (42.55%) were very low quality. The results of data synthesis showed that Xuebijing injection combined treatment increased the total effectiveness rate of AP patients (RR = 1.19, 95% CI 1.17-1.23, p < 0.0001), and there was no heterogeneity between studies (I2 = 0.0%, p = 0.589). Compared with the control group, Xuebijing injection group shortened the abdominal pain and distension relief time in AP patients (WMD = -1.69, 95% CI -1.88--1.50, p < 0.0001; WMD = -1.48, 95% CI -1.74--1.23, p < 0.0001), with high heterogeneity (I2 = 84.3%, p = 0.000; I2 = 72.2%, p = 0.000). Serum amylase level was also reduced (WMD = -2.06, 95% CI -2.47--1.64, p < 0.0001), with significant heterogeneity (I2 = 71.6%, p = 0.000). A total of one SR reported adverse drug reaction (ADR), no ADRs were observed in the control group. Conclusion: Although the quality of the evidence is not high, it can still reflect the clinical value of Xuebijing injection as an analgesic and anti-inflammatory traditional Chinese medicine in the treatment of AP/SAP. Therefore, future clinical studies should focus on the long-term efficacy and adverse reactions of drugs. Systematic Review Registration: (website), identifier (registration number).

Corrigendum: Efficacy and Safety of Shenqu Xiaoshi Oral Liquid Compared With Domperidone Syrup in Children With Functional Dyspepsia.

[This corrects the article DOI: 10.3389/fphar.2022.831912.].

Research Hotspots and Trends in Music Therapy Intervention for Patients With Dementia: A Bibliometrics and Visual Analysis of Papers Published From 2010 to 2021.

Background: As a serious public health problem, dementia has placed a heavy burden on society and families. Evidence suggests that the use of music therapy as a non-pharmacological intervention has certain advantages with respect to reducing the behavioral and psychological symptoms of dementia (BPSD) and improving the cognition and mental status of dementia patients. However, research trends and hotspots regarding music therapy intervention for dementia analysis have not been systematically studied via bibliometric analysis. Methods: We searched the Web of Science Core Collection (WoSCC) for texts published between January 1, 2010, and October 31, 2021, and visualized country, institution, journal, keyword co-occurrence, keyword emergence and keyword clustering. Results: A total of 217 articles from the WoSCC database were analyzed. In this research field, the annual number of publications has generally shown a slowly increasing trend, and the United States has the most publications and the most frequent cooperation among countries. University College London (UCL) has the most extensive influence among research institutions. Among articles, those published in the JOURNAL OF ALZHEIMER'S DISEASE were the most numerous, with 20 such articles being published, accounting for 9.22% (20/217) of the total. Comprehensive analysis of five clusters via biclustering shows that the research hotspots in this field during the past 11 years have mainly focused on the autobiographical memory, cognitive function, mental state and BPSD of dementia patients. Conclusion: This study conducted a bibliometric and visual analysis of relevant studies concerning music therapy intervention for dementia patients. Psychological problems faced by dementia patients and the topics of quality of life, individualized music therapy, the mental state of caregivers and other related topics may be important research directions in the future. Therefore, the question of how to develop standardized research protocols and identify unified efficacy evaluation indicators should be a focus of and difficulty for future research.

Efficacy and Safety of Shenqu Xiaoshi Oral Liquid Compared With Domperidone Syrup in Children With Functional Dyspepsia.

Background: Treatment of functional dyspepsia (FD) in children is generally symptomatic and unsatisfactory. Traditional Chinese medicines, such as Shenqu Xiaoshi Oral Liquid (SXOL), have been recommended to alleviate dyspeptic symptoms. However, evidence of their safety and efficacy remains limited to date. AIM: To assess whether 2 weeks of therapy with SXOL was non-inferior to domperidone syrup in children with FD. Methods: In this randomized, double-blind, double-simulated, non-inferiority, multi-center clinical trial, we recruited children (3-14 years) with FD according to the Rome IV criteria from 17 tertiary medical centers across China. Patients were randomly allocated (1:1) to receive SXOL or domperidone syrup for 2 weeks. We compared the participants' clinical scores from both groups based on the severity and frequency of dyspepsia symptoms according to Rome IV criteria (0, 1, 2, and 4 weeks after randomization). The primary endpoint was the total response rate, which was defined as the proportion of patients with a decrease of 30% or more in the FD symptoms clinical score from baseline, at the end of the 2-weeks treatment. A non-inferiority margin of -10% was set. Secondary endpoints and adverse events were assessed. This trial is registered with www.Chictr.org.cn, number ChiCTR1900022654. Results: Between February 2019 and March 2021, a total of 373 patients were assessed for eligibility, and 356 patients were enrolled and randomized. The clinical response rate at week two was similar for SXOL [118 (83.10%) of 142] and domperidone [128 (81.01%) of 158]; difference 2.09; 95% CI -6.74 to 10.71, thereby establishing non-inferiority. The total FD symptom scores were significantly improved in the two groups at 1-, 2-, and 4-weeks follow-up periods (p < 0.005). The decrease in symptom score compared with the baseline were similar between these two groups. Over the total study period, 10 patients experienced at least one treatment-related adverse event [six (3.37%)] in the SXOL group, four [(2.25%) in the domperidone group], although no serious adverse event was noted. Conclusion: Treatment with SXOL effectively improves dyspeptic symptoms and is well tolerated. In addition, it is not inferior to domperidone syrup and leads to sustained improvement in Chinese children with FD.

Acupuncture for Relieving Abdominal Pain and Distension in Acute Pancreatitis: A Systematic Review and Meta-Analysis.

Background: Clinical evidence suggests that acupuncture is effective for relieving abdominal pain and distension in acute pancreatitis (AP). However, there is a lack of systematic reviews and meta-analyses that provide high-quality evidence of the efficacy and safety of acupuncture in this context. Aim: To assess the efficacy and safety of acupuncture for relieving abdominal pain and distension in AP. Methods: We searched the PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, VIP, and China Biomedical Literature databases. Randomized controlled trials of acupuncture plus routine treatment (RT) vs. RT alone or RT plus sham/placebo acupuncture were included. Primary outcomes included total effectiveness rate, VAS scores for abdominal pain and distension, and time until relief of abdominal pain and distension. Secondary outcomes included time until recovery of bowel sound, time until first defecation, length of hospital stay, and APACHE II score. Results: Nineteen eligible original studies (n = 1,503) were included. The results showed that acupuncture in combination with RT had a significant advantage in terms of increasing the total effectiveness rate [risk ratio: 1.15; 95% confidence interval (CI): 1.06-1.24; P = 0.001]. Acupuncture also reduced the VAS score for abdominal pain [weighted mean difference (WMD): -1.45; 95% CI: -1.71 to -1.19; P < 0.0001] and the VAS score for abdominal distension (WMD: -0.71; 95% CI: -1.04 to -0.37; P < 0.0001) in patients with AP. Other results also showed the efficacy of acupuncture. One study reported adverse events after acupuncture. Conclusion: Acupuncture in combination with RT has a better effect than RT alone for relieving abdominal pain and distension in AP. More rigorous studies are needed to confirm this result. Systematic Review Registration: PROSPERO CRD42019147503 (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=147503).

[YUAN Qing's experience of Tiaoshen acupuncture in treating autism spectrum disorder].

YUAN Qing's clinical experience in treating autism spectrum disorder using Tiaoshen (regulating the spirit) acupuncture is summarized. YUAN Qing believes that the basic pathogenesis of children with autism spectrum disorder is due to the impairment of brain essence and heart mind. Thus regulating the spirit, especially adjusting brain essence and heart mind is essential during clinical treatment. The main acupoints on the head (brain tri-points, four-spirit points, spirit setting points, mental tri-points, spirit waking-up points and foot mental points) are used to adjust brain essence, and hand mental tri-points (Shenmen[HT 7], Neiguan[PC 6] and Laogong[PC 8]) are used for adjusting heart mind, and emphasizing the importance of the spirit of the doctor and the children's parents.

Acupuncture for heart failure: a Bayesian network systematic review and meta-analysis protocol.

BACKGROUND: Heart failure (HF) is the final stage of cardiovascular disease development, and clinical studies on acupuncture for the treatment of HF are increasing. However, the efficacy and safety of these acupuncture methods are unclear. The purpose of this study is to conduct a meta-analysis of the relevant randomized controlled trials (RCTs) to explain their efficacy and safety through high-quality evidence. METHODS: The databases of the Cochrane Library, PubMed, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), Wan-fang, and VIP will be searched from inception date to June 2021. The search will not be restricted by language. This study will include RCTs of various acupuncture methods for HF. Study selection, data extraction, and research quality assessments will be conducted independently by two researchers. The primary outcome is the efficacy rate and heart function, the secondary outcomes are quality of life scores, rehospitalization, and adverse reactions/events. The software RevMan 5.3 and Aggregate Data Drug Information System (ADDIS) will be used for network meta-analysis (NMA). Risk of bias, meta-regression, subgroup analysis, and sensitivity analysis will be performed, and the quality of evidence will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. DISCUSSION: This study will confirm the efficacy and safety of acupuncture in improving the clinical symptoms and heart function of HF, or elucidate which method of acupuncture is better suited to this purpose.

Overexpression of MAL2 Correlates with Immune Infiltration and Poor Prognosis in Breast Cancer.

BACKGROUND: Myelin and lymphocyte, T cell differentiation protein 2 (MAL2) is highly expressed in various cancers and associated with the development and prognosis of cancer. However, the relationship between MAL2 and breast cancer requires further investigation. This study aimed to explore the prognostic significance of MAL2 in breast cancer. METHODS: MAL2 expression was initially assessed using the Oncomine database and The Cancer Genome Atlas (TCGA) database and verified by quantitative real-time polymerase chain reaction (RT-qPCR). The chi-square test or Fisher's exact test was used to explore the association between clinical characteristics and MAL2 expression. The prognostic value of MAL2 in breast cancer was assessed by the Kaplan-Meier method and Cox regression analysis. Gene set enrichment analysis (GSEA) was performed to identify the biological pathways correlated with MAL2 expression in breast cancer. Besides, a single-sample GSEA (ssGSEA) was used to assess the relationship between the level of immune infiltration and MAL2 in breast cancer. RESULTS: Both bioinformatics and RT-qPCR results showed that MAL2 was expressed at high levels in breast cancer tissues compared with the adjacent tissues. The chi-square test or Fisher's exact test indicated that MAL2 expression was related to stage, M classification, and vital status. Kaplan-Meier curves implicated that high MAL2 expression was significantly associated with the poor prognosis. Cox regression models showed that high MAL2 expression could be an independent risk factor for breast cancer. GSEA showed that 14 signaling pathways were enriched in the high-MAL2-expression group. Besides, the MAL2 expression level negatively correlated with infiltrating levels of eosinophils and plasmacytoid dendritic cells in breast cancer. CONCLUSION: Overexpression of MAL2 correlates with poor prognosis and lower immune infiltrating levels of eosinophils and plasmacytoid dendritic cells in breast cancer and may become a biomarker for breast cancer prognosis.

A Network Pharmacology and Molecular Docking Strategy to Explore Potential Targets and Mechanisms Underlying the Effect of Curcumin on Osteonecrosis of the Femoral Head in Systemic Lupus Erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a refractory immune disease, which is often complicated with osteonecrosis of the femoral head (ONFH). Curcumin, the most active ingredient of Curcuma longa with a variety of biological activities, has wide effects on the body system. The study is aimed at exploring the potential therapeutic targets underlying the effect of curcumin on SLE-ONFH by utilizing a network pharmacology approach and molecular docking strategy. METHODS: Curcumin and its drug targets were identified using network analysis. First, the Swiss target prediction, GeneCards, and OMIM databases were mined for information relevant to the prediction of curcumin targets and SLE-ONFH-related targets. Second, the curcumin target gene, SLE-ONFH shared gene, and curcumin-SLE-ONFH target gene networks were created in Cytoscape software followed by collecting the candidate targets of each component by R software. Third, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Eventually, a gene-pathway network was constructed and visualized by Cytoscape software; key potential central targets were verified and checked by molecular docking and literature review. RESULTS: 201 potential targets of curcumin and 170 related targets involved in SLE-ONFH were subjected to network analysis, and the 36 intersection targets indicated the potential targets of curcumin for the treatment of SLE-ONFH. Additionally, for getting more comprehensive and accurate candidate genes, the 36 potential targets were determined to be analyzed by network topology and 285 candidate genes were obtained finally. The top 20 biological processes, cellular components, and molecular functions were identified, when corrected by a P value ≤ 0.05. 20 related signaling pathways were identified by KEGG analysis, when corrected according to a Bonferroni P value ≤ 0.05. Molecular docking showed that the top three genes (TP53, IL6, VEGFA) have good binding force with curcumin; combined with literature review, some other genes such as TNF, CCND1, CASP3, and MMP9 were also identified. CONCLUSION: The present study explored the potential targets and signaling pathways of curcumin against SLE-ONFH, which could provide a better understanding of its effects in terms of regulating cell cycle, angiogenesis, immunosuppression, inflammation, and bone destruction.

Bufotenine and its derivatives: synthesis, analgesic effects identification and computational target prediction.

Natural product bufotenine (5) which could be isolated from Venenum Bufonis, has been widely used as a tool in central nervous system (CNS) studies. We present here its quaternary ammonium salt (6) which was synthesized with high yields using 5-benzyloxyindole as raw materials, and we firstly discover its analgesic effects in vivo. The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice. Moreover, the combination of compound 6 and morphine has a synergistic effect. We intended to explain the molecular mechanism of this effect. Therefore, 36 analgesic-related targets (including 15 G protein-coupled receptors, 6 enzymes, 13 ion channels, and 2 others) were systemically evaluated using reverse docking. The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase (AChE) or α4ß2 nicotinic acetylcholine receptor (nAChR). This study provides practitioners a new insight of analgesic effects.

Identifying potential treatments of COVID-19 from Traditional Chinese Medicine (TCM) by using a data-driven approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) has been widely used as an approach worldwide. Chinese Medicines (CMs) had been used to treat and prevent viral infection pneumonia diseases for thousands of years and had accumulated a large number of clinical experiences and effective prescriptions. AIM OF THE STUDY: This research aimed to systematically excavate the classical prescriptions of Chinese Medicine (CM), which have been used to prevent and treat Pestilence (Wenbing, Wenyi, Shiyi or Yibing) for long history in China, to obtain the potential prescriptions and ingredients to alternatively treat COVID-19. MATERIALS AND METHODS: We developed the screening system based on data mining, molecular docking and network pharmacology. Data mining and association network were used to mine the high-frequency herbs and formulas from ancient prescriptions. Virtual screening for the effective components of high frequency CMs and compatibility Chinese Medicine was explored by a molecular docking approach. Furthermore, network pharmacology method was used to preliminarily uncover the molecule mechanism. RESULTS: 574 prescriptions were obtained from 96,606 classical prescriptions with the key words to treat "Warm diseases (Wenbing)", "Pestilence (Wenyi or Yibing)" or "Epidemic diseases (Shiyi)". Meanwhile, 40 kinds of CMs, 36 CMs-pairs, 6 triple-CMs-groups existed with high frequency among the 574 prescriptions. Additionally, the key targets of SARS-COV-2, namely 3CL hydrolase (Mpro) and angiotensin-converting enzyme 2(ACE2), were used to dock the main ingredients from the 40 kinds by the LigandFitDock method. A total of 66 compounds components with higher frequency were docked with the COVID-19 targets, which were distributed in 26 kinds of CMs, among which Gancao (Glycyrrhizae Radix Et Rhizoma), HuangQin (Scutellariae Radix), Dahuang (Rhei Radix Et Rhizome) and Chaihu (Bupleuri Radix) contain more potential compounds. Network pharmacology results showed that Gancao (Glycyrrhizae Radix Et Rhizoma) and HuangQin (Scutellariae Radix) CMs-pairs could also interact with the targets involving in immune and inflammation diseases. CONCLUSIONS: These results we obtained probably provided potential candidate CMs formulas or active ingredients to overcome COVID-19. Prospectively, animal experiment and rigorous clinic studies are needed to confirm the potential preventive and treat effect of these CMs and compounds.

Total synthesis, chemical modification and structure-activity relationship of bufadienolides.

Bufadienolides are a type of natural cardiac steroids and originally isolated from the Traditional Chinese Medicine Chan'Su, they have been used for the treatment of heart disease in traditional remedies as well as in modern medicinal therapy with potent anti-tumor activities. Due to their unique molecular structures with unsaturated six-membered lactones attached to the steroid core, bufadienolides have received great attention in the synthetic organic community. This review presents total synthetic efforts to some representative bufadienolides, chemical modification of bufadienolides will also be given to discuss their structure-activity relationship in anti-tumor.

Efficacy of Lactobacillus-supplemented triple therapy for Helicobacter pylori infection in children: a meta-analysis of randomized controlled trials.

Therapy-related side effects and severe antimicrobial resistance still remain an obstacle to Helicobacter pylori eradication. This meta-analysis aimed to investigate the efficacy of Lactobacillus-supplemented triple therapy on H. pylori eradication rates and therapy-related side effects in children. Five studies involving 484 pediatric patients were included in our analysis. The pooled relative risk (RR) for eradication rates in the Lactobacillus group versus the control group was 1.19 [95% confidence interval (CI) 1.07-1.33]. In subgroup analyses based on dose and duration of Lactobacillus supplementation, the pooled RRs for eradication rates were 1.36 (95% CI 1.15-1.60) in the high-dose group, 1.08 (95% CI 0.86-1.35) in the low-dose group, 1.24 (95% CI 1.06-1.46) in the long-term group, and 1.17 (95% CI 0.96-1.44) in the short-term group. With respect to side effects, Lactobacillus supplementation significantly reduced the incidence of diarrhea (RR = 0.30, 95% CI 0.10-0.85).Conclusions: Lactobacillus, as an adjunct to triple therapy, can increase H. pylori eradication rates as well as reduce the incidence of therapy-related diarrhea in children. And a higher dose and a longer duration of supplementation may conduce to the positive impact of Lactobacillus on H. pylori eradication. What is Known: • Probiotics-supplemented triple therapy may be beneficial in improving H. pylori eradication rates and reducing therapy-related side effects in children. However, not all probiotics are beneficial to H. pylori eradication and the pooled outcomes based on different probiotics may be erroneously extrapolated to other ineffective strains. What is New: • Lactobacillus, as an adjunct to triple therapy, can increase H. pylori eradication rates as well as reduce the incidence of therapy-related diarrhea in children.