Associations between maternal serum phytoestrogens and liver function markers: a cross-sectional study from China.

Phytoestrogens (PEs) may harm liver function. However, studies in pregnant women are limited. Our study was conducted in pregnant women to assess the effect of serum PEs on liver function markers. We conducted a cross-sectional study focusing in the first trimester of pregnancy. A total of 352 pregnant women were enrolled in the study. We used generalized linear model (GLM) to explore the associations between each PE and each marker of liver function. We used Quantile g-computation (Qgcomp) and Bayesian kernel machine regression (BKMR) models to explore the associations between mixed exposure to all PEs and liver function markers. The GLM results showed that equol (EQU), daidzein (DAD), genistein (GEN), enterolactone (ENT), and enterodiol (END) were negatively correlated with albumin (ALB). DAD and GEN were associated with elevated alanine aminotransferase (ALT). DAD, GEN, naringin (NAR), and glycitein (GLY) were related to elevated aspartate aminotransferase (AST). Mixed exposure model results showed that the mixture of PEs was associated with reduced ALB. Our results support the existence of associations between PEs and maternal liver function in the first trimester. Emphasizing the detrimental associations between serum PEs and liver function in pregnant women is essential to ensure maternal liver health during pregnancy.

Hot and cold tumors: Immunological features and the therapeutic strategies.

The "hotness" or "coldness" of the tumors are determined by the information of the cancer cells themselves, tumor immune characteristics, tumor microenvironment, and signaling mechanisms, which are key factors affecting cancer patients' clinical efficacy. The switch mechanism of "hotness" and "coldness" and its corresponding pathological characteristics and treatment strategies are the frontier and hot spot of tumor treatment. How to distinguish the "hotness" or "coldness" effectively and clarify the causes, microenvironment state, and characteristics are very important for the tumor response and efficacy treatments. Starting from the concept of hot and cold tumor, this review systematically summarized the molecular characteristics, influencing factors, and therapeutic strategies of "hot and cold tumors," and analyzed the immunophenotypes, the tumor microenvironment, the signaling pathways, and the molecular markers that contribute to "hot and cold tumors" in details. Different therapeutic strategies for "cold and hot tumors" based on clinical efficacy were analyzed with drug targets and proteins for "cold and hot tumors." Furthermore, this review combines the therapeutic strategies of different "hot and cold tumors" with traditional medicine and modern medicine, to provide a basis and guidance for clinical decision-making of cancer treatment.

Alterations in the phytochemical composition and antioxidant activity of Ligustrum robustum according to continuous wet- and dry-heat treatment.

Small-leaved Kuding tea (SLKDT) obtained from Ligustrum robustum is a traditional tea substitute in southern China and has a range of physiological effects. However, the changes in its phytochemical composition after various heat treatments are not reported yet. Thus, the phytochemical composition and antioxidant activities of fresh leaves of SLKDT (LrF1) and SLKDT after high-temperature wet-heat treatment (LrF2) and wet- and dry-heat treatments (LrF3) were assessed using liquid chromatography-mass spectrometry, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities and lipid peroxidation inhibition activity of LrF1 and LrF3 were investigated. The results indicated that the phytochemical composition of LrF1, LrF2, and LrF3 was significantly different. Overall, 258 and 83 differential constituents, respectively, were obtained in LrF1 versus LrF2 and LrF2 versus LrF3. The differential constituents mainly included amino acids and their derivatives, nucleosides, flavonoids, terpenoids, simple phenylpropanoids, and coumarins. After heat treatment, SLKDT exhibited obvious changes in sensory characteristics and physiological properties, which may be related to the changes in the levels of amino acids, linalool, beta-geraniol, myricetin, naringin, fraxetin, and isoacteoside. Moreover, the antioxidant activities significantly changed after heat treatment of SLKDT. Overall, our study demonstrated that heat treatment can alter the phytochemical composition of SLKDT, thus affecting its sensory properties and physiological properties. PRACTICAL APPLICATION: This study preliminarily assessed the changes in the composition of small-leaved Kuding tea (SLKDT) after various heat treatments and revealed that the composition of SLKDT tea can be adjusted by various heat and temperature treatments.

Qingdai Decoction suppresses prostate cancer growth in lethal-stage prostate cancer models.

ETHNOPHARMACOLOGICAL RELEVANCE: Contemporary therapy for advanced castration-resistant prostate cancer (CRPC) employs reagents such as enzalutamide and abiraterone acetate targeting the androgen receptor (AR) transcription axis only provide a temporary response and rapidly develop resistance. Additionally, neuroendocrine prostate cancer (NEPC) is an AR pathway-independent and lethal-stage prostate cancer with no standard therapy. Qingdai Decoction (QDT), a traditional Chinese medicine formula, has various pharmacological activities and was widely used for the treatment of different diseases including prostatitis which may contribute to prostate cancer development. AIM OF THE STUDY: This study aims to explore the anti-tumor role and potential mechanism of QDT on prostate cancer. MATERIAL AND METHODS: CRPC prostate cancer cell models and xenograft mice models were established for research. The effect of TCMs on cancer growth and metastasis were determined by CCK-8, wound-healing assays and the PC3-xenografted mice model. The toxicity of QDT in the major organs was investigated by H&E staining. The compound-target network was analyzed with network pharmacology. The correlation of QDT targets with prostate cancer patient's prognosis was analyzed with multiple prostate cancer patient cohorts. The expression of related proteins and mRNA were detected by western blot and real-time PCR. The gene knockdown was achieved with CRISPR-Cas13 technology. RESULTS: By integrating functional screening, network pharmacology analysis, CRISPR-Cas13 directed RNA targeting, and molecular biology validation in different prostate cancer models and clinical prostate cancer cohorts, we found that Qingdai Decoction (QDT), a Traditional Chinese Medicine, can repress cancer growth in advanced prostate cancer models in vitro and in vivo in an AR independent manner by targeting NOS3, TGFB1, and NCOA2. CONCLUSION: This study not only identified QDT as a novel drug for lethal-stage prostate cancer treatment but also provided an extensive Integrative research paradigm for investigating the roles and mechanisms of TCMs for the treatment of other diseases.

Gut Bacterial Diversity and Community Structure of Spodoptera exigua (Lepidoptera: Noctuidae) in the Welsh Onion-producing Areas of North China.

Gut microbiota play an important role in digestion, development, nutritional metabolism, and detoxification in insects. However, scant information exists on the gut bacterial variation, composition, and community structure of the beet armyworm, Spodoptera exigua (Hübner), and how its gut microbiota has adapted to different geographical environments. Using 16S rRNA high-throughput sequencing technology, we detected 3,837,408 high-quality reads and 1,457 operational taxonomic units (OTUs) in 47 gut samples of S. exigua collected from ten sites in northern China. Overall, we identified 697 bacterial genera from 30 phyla, among which Proteobacteria and Firmicutes were the most dominant phyla. Gut bacterial alpha-diversity metrics revealed significant differences among these populations. We detected the highest alpha bacterial diversity in Xinming, northern Liaoning Province, and the lowest bacterial diversity in Zhangwu, western Liaoning Province. Beta diversity indicated that the gut microbial community structure of S. exigua in Liaoning Province was significantly different from that of other populations. There was a similar microbial community structure among populations in the adjacent province, suggesting that the environment influences bacterial succession in this pest. Finally, PICRUSt analysis demonstrated that microbial functions closely associated with the gut microbiomes mainly included membrane transport, carbohydrate metabolism and replication, and amino acid metabolism.

Traditional use and safety evaluation of combination Traditional Chinese Medicine in European registration: with XiaoYao Tablets as an example.

Mental health disorders such as stress, anxiety, depression and insomnia caused by COVID-19 have attracted worldwide attention. Traditional Chinese medicines (TCMs) have been proven to be a safe and effective option for treating mental health disorders. Recently, after assessing its efficacy and safety fully, the Netherlands Medicines Evaluation Board approved XiaoYao Tablets as a traditional herbal medicinal product (THMP), indicated for an alternative self-care for patients in Europe to relieve the symptoms of mental stress and exhaustion. Despite the fact that TCMs have gradually become one of the therapeutic choices worldwide, to-date, only a few TCMs have been successfully registered in the European Union (EU) as THMPs, and XiaoYao Tablets is the first successfully registered combination TCM from China. In this article, traditional use efficacy and clinical safety of XiaoYao Tablets in the treatment of mental health disorders were summarized and analyzed from the perspective of traditional use registration (TUR). Additionally a safety evolution pathway of combination TCMs was established. This article will not only seek to enhance our understanding about traditional use efficacy and clinical safety of XiaoYao Tablets, but also summarize the experience of XiaoYao Tablets as the first successfully registered combination TCM from China, which could serve as role model for the others to overcome registration difficulties in the EU.

Jianpi Jiedu Recipe inhibits colorectal cancer liver metastasis via regulating ITGBL1-rich extracellular vesicles mediated activation of cancer-associated fibroblasts.

BACKGROUND: Extracellular vesicles (EVs) contribute greatly to the formation of pre-metastatic niche and tumor metastasis. Our previous study has revealed that tumor-derived ITGBL1 (integrin beta- like 1)-rich EVs activate fibroblasts through the NF-κB signaling to promote colorectal cancer (CRC) metastasis. Targeting ITGBL1-loaded EVs may be a new and effective therapy for treating CRC metastasis. Simultaneously, our preliminary clinical trial has demonstrated that Jianpi Jiedu Recipe (JPJDR) was an ideal alternative traditional Chinese medicine for the prevention and treatment of CRC metastasis. However, the underlying mechanism of JPJDR in the prevention of CRC metastasis is not clear. In this study, we will investigate the regulatory effect of JPJDR on ITGBL1 levels in CRC-derived EVs, and to detect how JPJDR regulate ITGBL1-rich EVs mediated activation of fibroblasts to inhibit CRC metastasis. METHODS: EVs derived from CRC cells with/without JPJDR treatment were obtained by ultracentrifugation, following by characterization with electron microscopy, LM10 nanoparticle characterization system and western blot. The migration and growth of CRC cells were tested by transwell assay, wound healing assay and colony formation assay. The effect of JPJDR on the fibroblasts-activation associated inflammatory factors including IL-6, IL-8 and α-SMA was detected by real-time PCR. The levels of IL-6, IL-8 and α-SMA in the cell culture supernatant were detected by ELISA. The protein expressions of TNFAIP3, ITGBL1, p-NF-κB, IκBα and ß-actin were detected by western blot. Liver metastasis model in mice was established by injecting MC38 single cell suspension into the spleen of mice to observe the effect of JPJDR on CRC liver metastasis. Immunohistochemistry were applied to detect the expression of ITGBL1 and TNFAIP3 in the liver metastatic tissues. Tissue immunofluorescence detection was performed to observe the regulatory effect of JPJDR on the ITGBL1-NF-κB signaling pathway. Cancer-associated fibroblasts (CAFs) in the liver metastatic tissues were sorted and characterized by platelet-derived growth factor receptor ß (PDGFRß) with flow cytometry, following by the detection of inflammatory factors including IL-6, IL-8 and α-SMA using real-time PCR. RESULTS: JPJDR reduced the ITGBL1 levels in CRC cells-derived EVs. JPJDR inhibited the migration and growth of CRC cells via regulating ITGBL1-rich EVs mediated fibroblasts activity. Mechanically, JPJDR decreased fibroblasts activation by regulating ITGBL1-rich EVs mediated TNFAIP3-NF-κB signaling. Further in vivo experiments demonstrated that JPJDR reduced CRC liver metastasis by regulating ITGBL1-rich EVs secretion from CRC and blocked the fibroblasts activation by regulating ITGBL1-TNFAIP3- NF-κB signaling. CONCLUSION: Our research demonstrated that JPJDR preventd CRC liver metastasis via down-regulating CRC-derived ITGBL1-loaded EVs mediated activation of CAFs, providing the experimental evidence for the clinical application of JPJDR in the prevention and treatment of CRC metastasis. More importantly, our study confirmed the great benefits of therapeutic targeting the EVs-mediated metastasis and warranted future clinical validation.

Mutation breeding of Aspergillus niger by atmospheric room temperature plasma to enhance phosphorus solubilization ability.

Background: Phosphorus (P) is abundant in soils, including organic and inorganic forms. Nevertheless, most of P compounds cannot be absorbed and used by plants. Aspergillus niger v. Tiegh is a strain that can efficiently degrade P compounds in soils. Methods: In this study, A. niger xj strain was mutated using Atmospheric Room Temperature Plasma (ARTP) technology and the strains were screened by Mo-Sb Colorimetry with strong P-solubilizing abilities. Results: Compared with the A. niger xj strain, setting the treatment time of mutagenesis to 120 s, four positive mutant strains marked as xj 90-32, xj120-12, xj120-31, and xj180-22 had higher P-solubilizing rates by 50.3%, 57.5%, 55.9%, and 61.4%, respectively. Among them, the xj120-12 is a highly efficient P solubilizing and growth-promoting strain with good application prospects. The growth characteristics such as plant height, root length, and dry and fresh biomass of peanut (Arachis hypogaea L.) increased by 33.5%, 43.8%, 43.4%, and 33.6%, respectively. Besides available P, the chlorophyll and soluble protein contents also vary degrees of increase in the P-solubilizing mutant strains. Conclusions: The results showed that the ARTP mutagenesis technology can improve the P solubilization abilities of the A. niger mutant strains and make the biomass of peanut plants was enhanced of mutant strains.

San-Wu-Huang-Qin decoction attenuates tumorigenesis and mucosal barrier impairment in the AOM/DSS model by targeting gut microbiome.

BACKGROUND: A classic herbal formula San-Wu-Huang-Qin (SWHQ) decoction has been widely used in clinical practices to prevent and treat colorectal cancer (CRC) for years, but its anti-tumorigenic properties and the underlying mechanisms remain undetermined. PURPOSE: The present study used a CRC mouse model to clarify whether and how SWHQ suppresses tumorigenesis. METHODS: Different doses of SWHQ were gavaged to the AOM/DSS model mice to examine its anti-tumor efficacy in comparison with the positive control drug Aspirin. The underlying microbiota-driven anti-tumor action of SWHQ was proven with bacterial manipulations by fecal microbial transplantation (FMT) in vivo and anaerobic culturing in vitro. RESULTS: SWHQ decoction dose-dependently reduced colonic tumor numbers/loads of AOM/DSS models and suppressed their disease activity index scores. SWHQ also recovered epithelial MUC2 secretion and colonic tight junction protein (ZO-1 and claudin1) expression in the mouse model. Such inhibitory impact on tumorigenesis and mucosal barrier impairment was found to be associated with modulation of gut dysbiosis, particularly for suppressing lipopolysaccharide (LPS) producers. The FMT experiment confirmed the substantial contribution of SWHQ-reshaped microbiota to anti-tumor function and mucosal barrier protection. Moreover, LPS-activated TLR4/NF-κB signaling and its downstream pro-inflammatory factors were significantly suppressed in the colon of SWHQ-treated models and SWHQ-reshaped microbiota recipients. CONCLUSIONS: We demonstrated that the SWHQ effectively inhibited tumorigenesis and protect mucosal barrier in CRC at least partially by targeting gut microbiota. This study provides scientific basis for the clinical usage of SWHQ in CRC intervention and prevention.

Library research support services in China's universities of traditional medicine: Understanding user requirements.

In this article, Ms Yihang Chen with her supervisor, Prof Lihong Zhou, reports on her MA in Library Science study aimed to identify user requirements of library research support services (RSS) at the universities of Traditional Chinese Medicine (TCM) in China. This study adopted an inductive qualitative approach, employed as a case study and 14 TCM researchers and academic librarians using semi-structured interviews. The research findings point to 28 RSS requirements in five main themes: mastering, planning, project, publication and electronic preservation stages. Although this research is situated in China, it has implications for libraries worldwide in supporting research into holistic and indigenous medicine. F.J.

Mufangji Decoction and Its Active Ingredient Patchouli Alcohol Inhibit Tumor Growth through Regulating Akt/mTOR-Mediated Autophagy in Nonsmall-Cell Lung Cancer.

BACKGROUND: Nonsmall-cell lung cancer (NSCLC) is the main type of lung cancer, whose morbidity and mortality rank first among malignant tumors. More than 70% of NSCLC patients are diagnosed at locally advanced or advanced stage, missing the best operation period. Chemotherapy and targeted therapy are important means for the treatment of advanced NSCLC, but various side effects seriously affect the curative effect and the life quality of NSCLC patients. Our previous clinical practice has shown that Mufangji Decoction, a classic traditional Chinese medicine, has a significant curative effect in the treatment of NSCLC, but the specific mechanism is not clear. This study intends to explore the potential mechanism of Mufangji Decoction and its active ingredient patchouli alcohol against NSCLC and to provide a scientific basis for the prevention and treatment of NSCLC by traditional Chinese medicine. METHODS: The in vivo and in vitro experiments were performed to evaluate the antitumor effects and investigate the underlying mechanism of Mufangji Decoction and its active ingredient patchouli alcohol. Network pharmacology was applied to analyze the effective ingredients and potential targets or signaling pathways of Mufangji Decoction. RESULTS: Our current study shows that Mufangji Decoction can effectively inhibit the growth of subcutaneous transplantation of NSCLC. The following network pharmacological analysis and in vivo experiment suggest that patchouli alcohol is one of the main active ingredients of Mufangji Decoction and exerts antitumor effects. Further mechanism investigation reveals that the antitumor effect of patchouli alcohol is related to the induction of Akt/mTOR signaling pathway-mediated autophagy in NSCLC cells. CONCLUSION: Mufangji Decoction and its active ingredient patchouli alcohol might exert their antitumor effects in NSCLC partly through regulating Akt/mTOR-mediated autophagy, providing the evidence that traditional Chinese medicine might be a key approach for NSCLC treatment via targeting the Akt/mTOR signal axis.

Exploring the Mechanism of Berberine Intervention in Ulcerative Colitis from the Perspective of Inflammation and Immunity Based on Systemic Pharmacology.

BACKGROUND: Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease of the colon and rectum. Recent studies found that berberine had effects on inflammatory diseases and immune diseases. METHODS: The PharmMapper database was used to predict the berberine potential target and GeneCards database and OMIM database were utilized to collect UC genes. The Cytoscape software was used to construct and analyze the networks and DAVID was utilized to perform enrichment analysis. Then, animal experiments were performed to validate the prediction results. The experimental rats were randomly divided into normal group (control group), model group, and berberine group. The general condition, body weight, gross morphology of colon tissue, and colonic mucosal damage index (CMDI) score were observed. The pathological changes of colon tissue were observed by H&E staining. The levels of serum interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and IL-4 were detected by ELISA. The expressions of IL-1ß, TNF-α, and IL-4 protein in colon tissue were detected by immunohistochemistry. RESULTS: A total of 211 Berberine's potential targets and 210 UC genes were obtained. The enrichment analysis showed that berberine may regulate inflammation, inflammatory cytokines, and their mediated inflammation signal pathways such as inflammatory bowel disease (IBD), rheumatoid arthritis, cytokine-cytokine receptor interaction, TNF, T cell receptor, Toll-like receptor, and JAK/STAT signaling pathway. Compared with the model group, the body mass of rats in the berberine group was significantly increased (P < 0.05); the general morphology and pathological changes of colon tissue were significantly improved; CMDI score, serum and colon tissue IL-1ß, TNF-α content, and protein expression were decreased significantly (P < 0.05); and IL-4 content and protein expression increased significantly (P < 0.05). CONCLUSION: Berberine can interfere with UC through related biological processes and signal pathways related to inflammation and immunity. In-depth exploration of the mechanism of berberine in the treatment of UC will provide a basis for clinical application.

Efficacy and Safety of Runzao Zhiyang Capsule as an Add-On Therapy for Chronic Eczema: A Systematic Review and Meta-Analysis.

BACKGROUND: Runzao Zhiyang capsule (RZC), an oral Chinese herbal medicine, has been widely used for chronic eczema in China for many years. This study aims to evaluate the efficacy and safety of RZC as an add-on therapy to conventional treatment for chronic eczema. METHODS: Randomized controlled trials (RCTs) assessing the efficacy and safety of RZC as an add-on therapy for chronic eczema were retrieved from eight literature databases from their inception to 31 August, 2020, including CNKI, WanFang, VIP, Sinomed, PubMed, Cochrane Library, Web of Science, and Embase. The Cochrane risk of bias tool was used to assess the methodological quality of the included studies. The data were analyzed by RevMan5.3 software. RESULTS: A total of 18 RCTs involving 1896 patients with chronic eczema were included. Compared with no oral treatment, RZC was superior on the total efficacy rate (TER) (RR = 1.45, 95% CI: 1.23 to 1.72, P < 0.0001), Eczema Area and Severity Index (EASI) (MD = -0.73, 95% CI: -0.90 to -0.56, P < 0.00001), and Visual Analogue Scale (VAS) for pruritus (MD = -2.76, 95%CI: -4.53 to -0.99, P=0.002). Similar results were also seen in a randomized, placebo-controlled trial. Compared with the antihistamine (AH) group, TER in the RZC combined with AH group was significantly higher (RR = 1.32, 95% CI: 1.21 to 1.43, P < 0.00001), and the EASI score (MD = -0.29, 95% CI: -0.38 to -0.20, P < 0.001), the VAS score (MD = -0.19, 95% CI: -0.23 to -0.15, P < 0.00001), and the level of serum total IgE (MD = -9.83 ng/ml, 95% CI: -11.66 to -8.00 ng/ml, P < 0.00001) decreased more significantly in the RZC combined with AH group. In terms of safety, mild gastrointestinal diseases occurred more frequently in the RZC group, and no serious adverse effect was reported. CONCLUSIONS: RZC as an add-on therapy to conventional treatment shows good effects on chronic eczema, and there is no severe side effect from short-term use of RZC. However, due to suboptimal quality of the included studies, more large-sample and high-quality RCTs are needed to improve the evidence quality.

Underlying mechanisms and drug intervention strategies for the tumour microenvironment.

Cancer occurs in a complex tissue environment, and its progression depends largely on the tumour microenvironment (TME). The TME has a highly complex and comprehensive system accompanied by dynamic changes and special biological characteristics, such as hypoxia, nutrient deficiency, inflammation, immunosuppression and cytokine production. In addition, a large number of cancer-associated biomolecules and signalling pathways are involved in the above bioprocesses. This paper reviews our understanding of the TME and describes its biological and molecular characterization in different stages of cancer development. Furthermore, we discuss in detail the intervention strategies for the critical points of the TME, including chemotherapy, targeted therapy, immunotherapy, natural products from traditional Chinese medicine, combined drug therapy, etc., providing a scientific basis for cancer therapy from the perspective of key molecular targets in the TME.

Establishment and validation of the quantitative analysis of multi-components by single marker for the quality control of Qishen Yiqi dripping pills by high-performance liquid chromatography with charged aerosol detection.

INTRODUCTION: Charged aerosol detection (CAD) has the merits of high sensitivity, high universality and response uniformity. The strategy that combines the quantitative analysis of multi-components by single marker (QAMS) with CAD has certain advantages for the quantification of multi-components. However, relevant research was limited. OBJECTIVES: To comprehensively investigate the crucial factors that affect the performance of the HPLC-CAD-QAMS approach and validate the credibility and feasibility of the method. METHODOLOGY: Multiple components of Qishen Yiqi dripping pills (QSYQ) were assayed using the high-performance liquid chromatography (HPLC)-CAD-QAMS approach. Some factors that affect the sensitivity and accuracy of the approach were sufficiently studied. After the method verification, principal component analysis (PCA) was applied to evaluate the quality consistency of three types of samples: normal samples, expired samples and negative samples. RESULTS: A HPLC-CAD-QAMS method was successfully developed for the multi-component determination of QSYQ. First, chromatographic conditions were optimised by a definitive screening design, and the optimised ranges of operating parameters were obtained with a Monte Carlo simulation method. Next, a new method to select the internal reference standards was successfully introduced based on the heatmap of Pearson correlation coefficients of the response factors. Then, the multi-point method was selected to calculate the relative correction factors, and a robustness test was conducted with Plackett-Burman design. Finally, the PCA was proved to be effective for the quality consistency evaluation of different samples. CONCLUSION: The developed HPLC-CAD-QAMS method can be a reliable and superior means for the multi-component quantitative analysis of QSYQ.

Effect of PRM1201 Combined With Adjuvant Chemotherapy on Preventing Recurrence and Metastasis of Stage III Colon Cancer: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Chemotherapy is the standard adjuvant treatment for colon cancer. Chinese herbal formula PRM1201 improves the efficacy of chemotherapy when used in combination with Cetuximab or Bevacizumab in patients with metastatic colorectal cancer. This study aims to explore the benefits of treatment with chemotherapy plus PRM1201 in the postoperative adjuvant setting. METHODS: In this parallel-group study, patients who had undergone curative resection for stage III colon cancer were randomly assigned to receive adjuvant chemotherapy (FOLFOX q2w for 6 months, or CapeOx q3w for 6 months) plus PRM1201 (chemo+PRM1201 group) or adjuvant chemotherapy plus placebo (chemo+placebo group). The primary endpoint was disease-free survival (DFS), and the secondary endpoints were quality of life (QOL) and toxicity. RESULTS: A total of 370 patients were randomly assigned to chemotherapy plus PRM1201 group (n = 184) and chemotherapy plus placebo group (n = 186). Up to October 30, 2019, 96 events of recurrence, metastasis, or death had been reported, of which 38 events were in the group of chemotherapy plus PRM1201 and 58 events in the chemo+placebo group. The 3-year DFS rate was 77.1 and 68.6% in the chemo+PRM1201 and chemo+placebo group, respectively (hazard ratio [HR], 0.63; 95% CI, 0.42 to 0.94). The QOL of patients in the chemo+PRM1201 group were significantly improved in terms of global quality of life, physical functioning, role functioning, emotional functioning, fatigue, and appetite loss. The incidence of grade 3 or 4 treatment-related adverse event (TRAEs) were similar between the two arms. CONCLUSIONS: Chemotherapy in combination with PRM1201 improved the adjuvant treatment of colon cancer. PRM1201 can be recommended as an effective option in clinical practice. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trials Registry, identifier ChiCTR-IOR-16007719.

Effects of mild moxibustion on intestinal microbiome and NLRP3 inflammasome in rats with 5-fluorouracil-induced intestinal mucositis.

OBJECTIVE: The present study investigated how mild moxibustion treatment affects the intestinal microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis (IM) induced with 5-fluorouracil (5-Fu). METHODS: Forty male Sprague-Dawley rats were randomly divided into control, chemotherapy, moxibustion and probiotics groups. The IM rat model was established by intraperitoneal injection of 5-Fu. Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days. Tissue morphology, serum levels of inflammatory factors and the expression levels of tight junction proteins, caspase-1, gasdermin D and NLRP3 were evaluated in colon tissue, through hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay, Western blotting, quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence. Gut microbiome profiling was conducted through 16S rRNA amplicon sequencing. RESULTS: Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins, reduced cell apoptosis and the expression levels of caspase-1, gasdermin D and NLRP3; they also decreased the serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1ß and IL-18, while increasing serum levels of IL-10. Moxibustion and probiotic treatments also corrected the reduction in α-diversity and ß-diversity in IM rats, greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapy-treated rats to levels observed in healthy animals. We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors. Finally, moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors. CONCLUSION: Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation. Moreover, moxibustion modulates the gut microbiota, likely via decreasing the expression levels of the NLRP3 inflammasome.

Reporting Quality of Randomized Controlled Trials for the Treatment of Eczema with Chinese Patent Medicine Based on the CONSORT-CHM Formulas 2017.

OBJECTIVE: Chinese patent medicine (CPM) has been widely used to treat eczema in mainland China for decades. This study aims to investigate circulating CPM for eczema in mainland China and to evaluate the reporting quality of randomized controlled trials (RCTs) of them by using the CONSORT-CHM formulas 2017 (Consolidated Standards of Reporting Trials for Chinese herbal medicine formulas 2017). METHODS: Circulating CPM with the indication for eczema was selected by searching three drug databases and confirmed by contacting the manufacturers. RCTs for the treatment of eczema with CPM were selected in four Chinese literature databases and four English literature databases from their inception to August 31, 2019. The reporting quality of included RCTs was assessed based on the CONSORT-CHM formulas 2017. A univariate analysis was conducted to identify the factors associated with the reporting quality. RESULTS: A total of 70 circulating CPMs had the indication for eczema. Among them, 21 CPMs with 144 RCTs reached the eligible criteria. The mean overall quality score (OQS) of 144 RCTs was 19.85 ± 2.73, which was much less than the maximum score of 38. Of the 38 items, 12 items were reported in over 70% of the trials, 6 items were reported in 50%-70% of the trials, and 16 items were reported in less than 50% of the trials. Publication after 2015 (P < 0.001) and the first author from a university hospital (P=0.010) were associated with the better reporting quality. CONCLUSION: There are a lot of circulating CPMs with the indication for eczema in mainland China, but both the quantity and the reporting quality of RCTs regarding those CPMs are suboptimal. It is necessary that authors and journal editors learn and adhere to the CONSORT-CHM formulas 2017 to enhance the reporting quality of RCTs for the treatment of eczema with CPM.

YYFZBJS ameliorates colorectal cancer progression in ApcMin/+ mice by remodeling gut microbiota and inhibiting regulatory T-cell generation.

BACKGROUND: Progression of Colorectal cancer (CRC) is influenced by single or compounded environmental factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. T cell, one of the main populations of effector immune cells in antitumor immunity, has been considered as a double-edged sword during the progression of CRC. Our previous studies indicate that traditional Chinese herbs (TCM) have potential anticancer effects in improving quality of life and therapeutic effect. However, little is known about the mechanism of TCM formula in cancer prevention. METHODS: Here, we used C57BL/6 J ApcMin/+ mice, an animal model of human intestinal tumorigenesis, to investigate the gut bacterial diversity and their mechanisms of action in gastrointestinal adenomas, and to evaluate the effects of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) on of colon carcinogenesis in vivo and in vitro. Through human-into-mice fecal microbiota transplantation (FMT) experiments from YYFZBJS volunteers or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. RESULTS: We report herein, YYFZBJS treatment blocked tumor initiation and progression in ApcMin/+ mice with less change of body weight and increased immune function. Moreover, diversity analysis of fecal samples demonstrated that YYFZBJS regulated animal's natural gut flora, including Bacteroides fragilis, Lachnospiraceae and so on. Intestinal tumors from conventional and germ-free mice fed with stool from YYFZBJS volunteers had been decreased. Some inflammation' expression also have been regulated by the gut microbiota mediated immune cells. Intestinal lymphatic, and mesenteric lymph nodes (MLN), accumulated CD4+ CD25+ Foxp3 positive Treg cells were reduced by YYFZBJS treatment in ApcMin/+ mice. Although YYFZBJS had no inhibition on CRC cell proliferation by itself, the altered Tregs mediated by YYFZBJS repressed CRC cancer cell growth, along with reduction of the phosphorylation of ß-catenin. CONCLUSIONS: In conclusion, we demonstrated that gut microbiota and Treg were involved in CRC development and progression, and we propose YYFZBJS as a new potential drug option for the treatment of CRC. Video abstract.

Traditional Chinese Medicine Combined With Chemotherapy and Cetuximab or Bevacizumab for Metastatic Colorectal Cancer: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Huangci Granule is a traditional Chinese medicine for treating metastatic colorectal cancer (mCRC). OBJECTIVE: To evaluate the efficacy and safety of Huangci Granule combination with chemotherapy and cetuximab (CET) or bevacizumab (BV) for treating mCRC. METHODS: We performed a randomized, controlled, and double-blind trial and recruited patients with mCRC who were planned to undergo chemotherapy combined with CET or BV. The treatment group was treated with Huangci Granule, while the control group was treated with placebo. Continuous treatment until disease progression, death, intolerable toxicity or up to 6 months. The primary endpoint was progression-free survival (PFS), and the secondary endpoint was quality of life and safety. RESULT: 320 patients were randomly assigned to receive treatment, including 200 first-line patients and 120 second-line patients. In the first-line treatment, the median PFS was 9.59 months (95% CI, 6.94-13.25) vs 6.89 months (95% CI, 4.99-9.52) in treatment group and control group (HR, 0.69; 95% CI, 0.50-0.97; P = 0.027). Chinese medicine was an independent factor affecting the PFS. In the second-line treatment, the median PFS was 6.51 months (95% CI, 4.49-9.44) vs 4.53 months (95% CI, 3.12-6.57) in the treatment group and control group (HR, 0.65; 95% CI, 0.45-0.95; P = 0.020). Compared with the control group, "role function," "social function," "fatigue," and "appetite loss" were significantly improved in the treatment (P < 0.05) and drug related grades 3 to 4 adverse events were less. CONCLUSION: Huangci Granule combined with chemotherapy and CET or BV can prolong the PFS of mCRC, improve the quality of life, reduce adverse reactions, and have good safety.