Clinical Efficacy and Adverse Effects of Bevacizumab in Combination with Chemotherapy for Metastatic Colorectal Cancer.

Objective: This study aims to investigate the efficacy of bevacizumab (BEV) in combination with chemotherapy for metastatic colorectal cancer (mCRC). Methods: A cohort of 121 patients diagnosed with mCRC and admitted to our hospital from May 2018 to October 2019 were selected for the study. The control group, comprising 64 patients, received chemotherapy alone, while the research group, consisting of 57 patients, underwent a combination of BEV and chemotherapy. Comparative analyses included an assessment of clinical outcomes, monitoring of tumor markers including Carcinoembryonic Antigen (CEA), Cancer Antigen 74-2 (CA74-2), and Carbohydrate Antigen 19-9 (CA19-9) before and after treatment, and a count of adverse effects during the treatment phase. A 3-year post-discharge follow-up was conducted to compare the survival prognosis between the two groups. Results: The research group exhibited a significantly higher objective response rate (ORR) and clinical benefit rate (CBR) compared to the control group (P < .05). Furthermore, CEA, CA74-2, and CA19-9 post-treatment levels were markedly lower in the research group (P < .05). No notable difference in the incidence of adverse reactions was observed between the two groups (P > .05). Importantly, the 3-year overall survival prognosis was superior in the research group (P < .05). Within the research group, patients treated with BEV combined with the XELIRI regimen chemotherapy demonstrated a higher CBR rate (P < .05). Conclusions: The combination of BEV and chemotherapy proves to be highly effective in treating mCRC, significantly enhancing the prognostic survival cycle of patients. This treatment modality holds promise for future clinical applications in managing patients with mCRC.

Integrated metabolomic and transcriptomic analyses provide insights into regulation mechanisms during bulbous stem development in the Chinese medicinal herb plant, Stephania kwangsiensis.

BACKGROUND: Stephania kwangsiensis Lo (Menispermaceae) is a well-known Chinese herbal medicine, and its bulbous stems are used medicinally. The storage stem of S. kwangsiensis originated from the hypocotyls. To date, there are no reports on the growth and development of S. kwangsiensis storage stems. RESULTS: The bulbous stem of S. kwangsiensis, the starch diameter was larger at the stable expanding stage (S3T) than at the unexpanded stage (S1T) or the rapidly expanding stage (S2T) at the three different time points. We used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and Illumina sequencing to identify key genes involved in bulbous stem development. A large number of differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) were identified. Based on the differential expression profiles of the metabolites, alkaloids, lipids, and phenolic acids were the top three differentially expressed classes. Compared with S2T, significant changes in plant signal transduction and isoquinoline alkaloid biosynthesis pathways occurred at both the transcriptional and metabolic levels in S1T. In S2T compared with S3T, several metabolites involved in tyrosine metabolism were decreased. Temporal analysis of S1T to S3T indicated the downregulation of phenylpropanoid biosynthesis, including lignin biosynthesis. The annotation of key pathways showed an up-down trend for genes and metabolites involved in isoquinoline alkaloid biosynthesis, whereas phenylpropanoid biosynthesis was not completely consistent. CONCLUSIONS: Downregulation of the phenylpropanoid biosynthesis pathway may be the result of carbon flow into alkaloid synthesis and storage of lipids and starch during the development of S. kwangsiensis bulbous stems. A decrease in the number of metabolites involved in tyrosine metabolism may also lead to a decrease in the upstream substrates of phenylpropane biosynthesis. Downregulation of lignin synthesis during phenylpropanoid biosynthesis may loosen restrictions on bulbous stem expansion. This study provides the first comprehensive analysis of the metabolome and transcriptome profiles of S. kwangsiensis bulbous stems. These data provide guidance for the cultivation, breeding, and harvesting of S. kwangsiensis.

RNA editing events and expression profiles of mitochondrial protein-coding genes in the endemic and endangered medicinal plant, Corydalis saxicola.

Corydalis saxicola, an endangered medicinal plant endemic to karst habitats, is widely used in Traditional Chinese Medicine to treat hepatitis, abdominal pain, bleeding hemorrhoids and other conditions. However, to date, the mitochondrial (mt) genome of C. saxicola has not been reported, which limits our understanding of the genetic and biological mechanisms of C. saxicola. Here, the mt genome of C. saxicola was assembled by combining the Nanopore and Illumina reads. The mt genome of C. saxicola is represented by a circular chromosome which is 587,939 bp in length, with an overall GC content of 46.50%. 40 unique protein-coding genes (PCGs), 22 tRNA genes and three rRNA genes were identified. Codon usage of the PCGs was investigated and 167 simple sequence repeats were identified. Twelve homologous fragments were identified between the mt and ct genomes of C. saxicola, accounting for 1.04% of the entire mt genome. Phylogenetic examination of the mt genomes of C. saxicola and 30 other taxa provided an understanding of their evolutionary relationships. We also predicted 779 RNA editing sites in 40 C. saxicola mt PCGs and successfully validated 506 (65%) of these using PCR amplification and Sanger sequencing. In addition, we transcriptionally profiled 24 core mt PCGs in C. saxicola roots treated with different concentrations of CaCl2, as well as in other organs. These investigations will be useful for effective utilization and molecular breeding, and will also provide a reference for further studies of the genus Corydalis.

Polysaccharide of Asparagus cochinchinensis (Lour.) Merr regulates macrophage immune response and epigenetic memory through TLR4-JNK/p38/ERK signaling pathway and histone modification.

BACKGROUND: Innate immune memory of macrophages is closely linked to histone modifications. While various studies have demonstrated that the polysaccharide of Asparagus cochinchinensis (Lour.) Merr (ACMP), extracted through alcohol-alkali extraction, enhances macrophages' non-specific immune function; no literature currently addresses whether ACMP's regulatory effect is related to innate immune memory and histone modification. PURPOSE: This study aims to investigate if ACMP induces innate immune memory emergence in macrophages via pattern recognition receptor (PRR). STUDY DESIGN: After co-incubating different doses of ACMP with RAW264.7 cells and BMDM cells, we observed changes in signaling pathways related to PRR and assessed the presence of innate immune memory phenomenon in the cells. METHODS: We observed the morphological characteristics of the ACMP using a scanning electron microscope, infrared spectrum, and HPLC pre-column derivatization method. We used q-PCR, Western blot, RNA-seq, and CUT&Tag-seq methods to examine ACMP's regulation of macrophage immune response and innate immune memory and explored its specific mechanism. RESULTS: ACMP, primarily composed of Man, GlcN, Rha, Fuc, GalA, Xyl, Glc, Gal, Ara, and, exhibited a molar ratio of each monosaccharide (1.41: 0.35: 0.49: 0.18: 1.00: 97.12: 0.36: 3.58: 1.14). ACMP regulated immunological function in macrophages through the TLR4-MAPK-JNK/p38/ERK pathway. ACMP induced elevated levels of chromosomal H3K4me1, enhancing TNF-α, IL-1ß, and other genes' responsiveness, allowing macrophages to develop innate immune memory to ACMP stimulation. CONCLUSION: This study first time demonstrates that ACMP regulates immunological function through the TLR4-MAPK-JNK/ERK/p38 signaling pathway, distinct from prior reports. ACMP induces innate immune memory in macrophages in response to its immune stimulation by promoting increased H3K4me1 on chromosomes. This mechanism may be crucial in how plant polysaccharides regulate macrophages and the body's immune function.

Acute kidney injury in acute promyelocytic leukemia: a possible adverse effect of high dose arsenic trioxide in obese patients.

Arsenic trioxide (ATO)-based regimens are standard in acute promyelocytic leukemia (APL). ATO-related nephrotoxicity has not been reported. We reviewed APL patients treated with ATO to identify cases of acute kidney injury (AKI). Clinically significant cases were characterized. Multivariate analysis was performed to identify predictors of idiopathic, clinically significant AKI. One hundred and eight patients were included. ATO dose was 0.15 mg/kg/day using actual body weight with no dose cap. Thirty-one (28.7%) AKI cases were identified, 10 (32.3%) clinically significant. Six were idiopathic; five required dialysis. The proportion with significant, idiopathic AKI was 15.8% in patients receiving >15mg ATO versus 0% in those receiving ≤15mg (p = 0.001). On multivariate analysis, only ATO dose was a significant predictor of clinically significant AKI (odds ratio of 1.91, 95%CI, 1.19-3.07, p = 0.007). High-dose ATO may be associated with significant nephrotoxicity. We recommend that ATO dose be capped at 15 mg to minimize toxicity for this curable disease.

Wheat peptides inhibit the activation of MAPK and NF-κB inflammatory pathways and maintain epithelial barrier integrity in NSAID-induced intestinal epithelial injury.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) has negative effects on the gastrointestinal tract, but the proton pump inhibitors currently in use only protect against gastrointestinal disease and may even make NSAID-induced enteropathy worse. Therefore, new approaches to treating enteropathy are required. This study aimed to investigate the protective effect of wheat peptides (WPs) against NSAID-induced intestinal damage in mice and their mechanism. Here, an in vivo mouse model was built to investigate the protective and reparative effects of different concentrations of WPs on NSAID-induced intestinal injury. WPs ameliorated NSAID-induced weight loss and small intestinal tissue damage in mice. WP treatment inhibited NSAID-induced injury leading to increased levels of oxidative stress and expression levels of inflammatory factors. WPs protected and repaired the integrity and permeability injury of the intestinal tight junction induced by NSAIDs. An in vitro Caco-2 cell model was built with lipopolysaccharide (LPS). WP pretreatment inhibited LPS-induced changes in the Caco-2 cell permeability and elevated the levels of oxidative stress. WPs inhibited LPS-induced phosphorylation of NF-κB p65 and mitogen-activated protein kinase (MAPK) signaling pathways and reduced the expression of inflammatory factors. In addition, WPs increased tight junction protein expression, which contributed to improved intestinal epithelial dysfunction. Our results suggest that WPs can ameliorate NSAID-induced impairment of intestinal barrier functional integrity by improving intestinal oxidative stress levels and reducing inflammatory factor expression through inhibition of NF-κB p65 and MAPK signaling pathway activation. WPs can therefore be used as potential dietary supplements to reduce NSAID-induced injury of the intestine.

[Comparison of fat determination methods and analysis of fatty acids in tea].

OBJECTIVE: Comparative analysis of two method for determining fat and analysis of fatty acid content in tea samples. METHODS: The content of freefatand total fat in tea was determined by Soxhlet extraction method and acid hydrolysis method, and the content of fatty acids were determined by gas chromatography. The composition and content of fatty acids in 21 tea samples from 5 regions were analyzed. RESULTS: The freefat content of tea determined by Soxhlet extraction method was significantly lower than that determined by acid hydrolysis method. The totalfat content in tea determined by acid hydrolysis method was consistent with the total amount of fatty acids determined by gas chromatography, and their content conformed to the logical relationshipsimultaneously. The totalfat content in tea ranged from 0.6 to 4.1 g/100 g, which in green tea, white tea, yellow tea, and black tea were 2.2, 1.8, 1.6 and 0.6 g/100 g, respectively. The content of free fat in tea was less than 58%, with 42%-80% of the fat existing in a bound form. The fatty acids in tea were mainly unsaturated fatty acids, accounting for 67.52%-99.03% of the total fatty acids. There were differences in the composition of fatty acids in different types of tea, with the proportion of unsaturated fatty acids in yellow tea accounting for 98.84% of the total fatty acids, which was significantly higher than that of green tea, white tea, and black tea. The fatty acids with high content in green tea(except Tang chi xiaolan tea, Bawangjian green tea and Liuxi yuye tea)were α-linoleic acid, linoleic acid, and palmitic acid. CONCLUSION: Theacid hydrolysis method is more suitable for the determination of fat in tea samples. The composition and content of fat and fatty acids in tea vary depending onfactors such as the type of tea and the degree of fermentation.

TMT-based quantitative proteomics revealed protective efficacy of Icariside II against airway inflammation and remodeling via inhibiting LAMP2, CTSD and CTSS expression in OVA-induced chronic asthma mice.

BACKGROUND: Asthma is a chronic inflammatory disorder in airways with typical pathologic features of airflow limitation, airway inflammation and remodeling. Icariside II (IS), derived from herbal medicine Herba Epimedii, exerts an anti-inflammatory property. However, underlying mechanisms with specifically targeted molecular expression by IS in asthma have not been fully understood, and whether IS could inhibit remodeling and EMT still remains unclear. PURPOSE: The study aimed to clarify therapeutic efficacy of IS for attenuating airway inflammation and remodeling in asthma, and illustrate IS-regulated specific pathway and target proteins through TMT-based quantitative proteomics. STUDY DESIGN AND METHODS: Murine model of chronic asthma was constructed with ovalbumin (OVA) sensitization and then challenge for 8 weeks. Pulmonary function, leukocyte count in bronchoalveolar lavage fluid (BALF), lung histopathology, inflammatory and fibrotic cytokines, and markers of epithelial-mesenchymal transition (EMT) were evaluated. TMT-based quantitative proteomics were performed on lung tissues to explore IS-regulated proteins. RESULTS: IS contributed to alleviative airway hyperresponsiveness (AHR) evidenced by declined RL and increased Cdyn. After IS treatment, we observed a remarked down-regulation of leukocyte count, inflammatory cytokines in BALF, and peribronchial inflammation infiltration. Goblet cell hyperplasia, mucus secretion and peribronchial collagen deposition were attenuated, with the level of TGF-ß and MMP-9 in BALF declined. Furthermore, IS induced a rise of Occludin and E-cadherin and a decline of N-cadherin and α-SMA in lung tissues. These results proved the protective property of IS against airway inflammation, remodeling and EMT. To further investigate underlying mechanisms of IS in asthma treatment, TMT-based quantitative proteomics were performed and 102 overlapped DEPs regulated by IS were identified. KEGG enrichment exhibited these DEPs were enriched in lysosome, phagosome and autophagy, in which LAMP2, CTSD and CTSS were common DEPs. WB, q-PCR and IHC results proofed expressional alteration of these proteins. Besides, IS could decrease Beclin-1 and LC3B expression with increasing p62 expression thus inhibiting autophagy. CONCLUSIONS: The study demonstrated IS could ameliorate AHR, airway inflammation, remodeling and EMT in OVA-induced chronic asthma mice. Our research was the first to reveal that inhibition of LAMP2, CTSD and CTSS expression in autophagy contributed to the therapeutic efficacy of IS to asthma.

Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships.

Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and fluorescence resonance energy transfer (FRET) assays were used to determine HIV-1 PR and Cat L PR inhibitions and identify structure-activity relationships. Molecular docking was also performed, to explore the diversification in bonding patterns of the active flavonoids upon binding to the two PRs. Three SB extracts (SBW, SB30, and SB60) and nine flavonoids inhibited HIV-1 PR with an IC50 range from 0.006 to 0.83 mg/mL. Six of the flavonoids showed 10~37.6% inhibition of Cat L PR at a concentration of 0.1 mg/mL. The results showed that the introduction of the 4'-hydroxyl and 6-hydroxyl/methoxy groups was essential in the 5,6,7-trihydroxyl and 5,7,4'-trihydroxyl flavones, respectively, to enhance their dual anti-PR activities. Hence, the 5,6,7,4'-tetrahydroxyl flavone scutellarein (HIV-1 PR, IC50 = 0.068 mg/mL; Cat L PR, IC50 = 0.43 mg/mL) may serve as a lead compound to develop more effective dual protease inhibitors. The 5,7,3',4'-tetrahydroxyl flavone luteolin also showed a potent and selective inhibition of HIV-1 PR (IC50 = 0.039 mg/mL).

Icariside â ¡ attenuates bleomycin-induced pulmonary fibrosis by modulating macrophage polarization.

ETHNOPHARMACOLOGICAL RELEVANCE: Numerous studies have provided evidence supporting the significant roles of icariin, in the prevention of multiple chronic diseases like diabetes, liver fibrosis, cardiac fibrosis, renal fibrosis, and pulmonary fibrosis. In particular, Icariside II (ISE II), a prominent flavonoid glycoside derived from Epimedium brevicornum Maxim, the principal metabolite of icariin, has demonstrated noteworthy anti-inflammatory and anti-oxidant properties, along with its ability to protect against lung remodeling. However, the research exploring ISE Ⅱ's application in treating pulmonary fibrosis remains limited. AIM OF THE STUDY: The aim of this study was to assess the therapeutic efficacy of ISE II in models of pulmonary fibrosis, while also investigating its potential mechanisms of action in cell signaling pathways. MATERIALS AND METHODS: An in vitro model of pulmonary fibrosis was established by treating NIH-3T3 cells with transforming growth factor-ß1 (TGF-ß1). Western blot, RT-qPCR, and scratch test were performed to assess the effect of ISE Ⅱ. In addition, a murine model of pulmonary fibrosis was induced by intratracheal instillation of bleomycin, and the therapeutic effect of ISE Ⅱ was tested by orally administering ISE Ⅱ at a dose of 10 mg/kg. Three weeks later, lung function, micro-CT, hydroxyproline content, pathological staining, and cytokines detection of BALF or serum were used to assess the anti-fibrosis effects of ISE Ⅱ. Next, immunofluorescence staining, flow cytometry, and in vivo transcriptomics were used to investigate the underlying mechanisms of action. RESULTS: Our data revealed a significant inhibitory effect of ISE Ⅱ on the upregulation of α-smooth muscle actin (α-SMA) and collagen production induced by TGF-ß1 in fibroblasts. Meanwhile, ISE Ⅱ exerted a therapeutic effect against bleomycin-induced pulmonary fibrosis in mice by improving lung function, decreasing collagen deposition, and reducing the expression of interleukin (IL)-1ß, tumor necrosis factor α (TNF-α), TGF-ß1 and platelet-derived growth factor (PDGF) in serum and bronchoalveolar lavage fluid (BALF). Additionally, ISE Ⅱ treatment effectively attenuated the infiltration of M2 macrophages, concurrently downregulating the expression level of M2 marker genes, such as CD206, arginase-1(Arg-1), and Chitinase-Like Protein 3 (YM-1). Importantly, we observed a statistically significant reduction in the M2 phenotype of interstitial macrophages (IMs). However, the impact of ISE Ⅱ on the M2 polarization of alveolar macrophages (AMs) did not reach statistical significance. Lastly, transcriptome sequencing results suggested that the anti-pulmonary fibrosis effects of ISE Ⅱ may be mediated by the suppression of the WNT/ß-catenin signaling pathway, which modulated M2 polarization in macrophages and contributed to the amelioration of pulmonary fibrosis. By immunohistochemical analysis, it was verified that ISE Ⅱ treatment dramatically inhibited the activation of ß-catenin in fibrosis murine. CONCLUSION: Our findings indicated that ISE Ⅱ exerted anti-fibrotic effects by inhibiting pro-fibrotic macrophage polarization. The underlying mechanism of action might be mediated by modulating the WNT/ß-catenin signaling pathway to inhibit the M2 program in IMs.

Statins Restore Endothelial Protection against Complement Activity in Obstructive Sleep Apnea: A Randomized Clinical Trial.

Rationale: Increased cardiovascular risk in obstructive sleep apnea (OSA) persists after continuous positive airway pressure (CPAP) and alternative therapies are needed. Impaired endothelial protection against complement is a cholesterol-dependent process that initiates endothelial inflammation in OSA, which increases cardiovascular risk. Objectives: To investigate directly whether lowering cholesterol improves endothelial protection against complement and its proinflammatory effects in OSA. Methods: Newly diagnosed patients with OSA (n = 87) and OSA-free controls (n = 32) participated. Endothelial cells and blood were collected at baseline, after 4 weeks of CPAP therapy, and again after 4 weeks of 10 mg atorvastatin versus placebo using a randomized, double-blind, parallel-group design. Primary outcome was the proportion of a complement inhibitor, CD59, on the endothelial cell plasma membrane in OSA patients after 4 weeks of statins versus placebo. Secondary outcomes were complement deposition on endothelial cells and circulating levels of its downstream proinflammatory factor, angiopoietin-2, after statins versus placebo. Results: Baseline expression of CD59 was lower, whereas complement deposition on endothelial cells and levels of angiopoietin-2 were greater, in patients with OSA compared with controls. CPAP did not affect expression of CD59 or complement deposition on endothelial cells in patients with OSA, regardless of adherence. Compared with placebo, statins increased expression of endothelial complement protector CD59 and lowered complement deposition in patients with OSA. Good CPAP adherence was associated with increased angiopoietin-2 levels, which was reversed by statins. Conclusions: Statins restore endothelial protection against complement and reduce its downstream proinflammatory effects, suggesting a potential approach to reduce residual cardiovascular risk after CPAP in patients with OSA. Clinical trial registered with www.clinicaltrials.gov (NCT03122639).

Regulation of ferroptosis and ACSL4-15LO1 pathway contributed to the anti-asthma effect of acupuncture.

Acupuncture has been frequently used in China for the treatment asthma for thousands of years. Ferroptosis was recently revealed to be involved in several pathological conditions including asthma. However, the detailed links between ferroptosis and airway inflammation in asthma, as well as the detailed regulation of acupuncture on these disorders remains unclear. Our results demonstrated that the non-haem Fe2+ level increased markedly in the lung tissue of mouse asthma model, and positively correlated with RL and IL-4 level in BALF. Furthermore, lipid peroxidation markers MDA and GSSG increased remarkably in OVA-induced experimental asthma mice. Up-regulation of lipid peroxidation associated proteins ACSL4 and15-LO1 was also observed in OVA-induced experimental asthma mice. To demonstrate the role of ferroptosis in asthma and the effect of acupuncture on these disorders, ferroptosis-induction agent erastin and ferroptosis-inhibition agent fer-1 were used, and our data demonstrated that erastin could augment lung inflammation and lipid peroxidation in OVA induced asthma model. Fer-1 was able to relieve AHR, lung inflammation, non-haem Fe2+ level, lipid peroxidation and ferroptosis related pathway ACSL4-15LO1 in OVA-induced experimental asthma mice. Acupuncture treatment alleviated RL, lung inflammation as well as type 2 cytokines IL-4 and IL-13 levels induced by OVA inhalation. What's more, acupuncture significantly reduced the MDA and GSSG levels, the non-haem Fe2+ level and ACSL4-15-LO1 proteins expression. Acupuncture also relieved erastin-induced exacerbation in lung inflammation and lipid peroxidation in ferroptosis. Acupuncture treatment could relieve ferroptosis related exacerbation in airway inflammation. Our study provided insights into the underlying mechanisms for the protective effects of acupuncture and highlighted a therapeutic potential of acupuncture treatment in the attenuation of lipid peroxidation and ferroptosis in asthma.

Effects of Baduanjin exercise on quality-of-life and exercise capacity in patients with heart failure: A systematic review and meta-analysis.

PURPOSE: Exercise training is an efficient non-pharmacological intervention for patients with heart failure (HF). This study aimed to objectively evaluate the effects of Baduanjin exercise on the quality of life (QOL) and exercise capacity in patients with HF. METHODS: PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and Wanfang data were searched from the date of their inception until 30 September 2022. All randomised controlled trials (RCTs) evaluating the effects of Baduanjin exercise on QOL and exercise capacity in patients with HF were selected. The primary outcomes were QOL, assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and exercise capacity, evaluated using the 6-min walking test (6-MWT). A meta-analysis was performed by comparing the MLHFQ domain scores. Review Manager 5.3 and Stata 14.0, were used for the data analysis. RESULTS: Baduanjin exercise showed a favourable improvement of the overall QOL (mean difference = -8.25; 95% confidence interval: -13.62 to -2.89; P = 0.003) and exercise capacity (mean difference = 118.49; 95% confidence interval: 52.57 to 184.41; P = 0.0004). Meta-analyses of the MLHFQ domain score indicated that Baduanjin exercise significantly improved the patients' physical (mean difference = -2.83; 95% confidence interval: -3.76, -1.90; P < 0.00001), emotional (mean difference = -2.52; 95% confidence interval: -3.67 to -1.37; P < 0.0001), and general QOL (mean difference = -2.61; 95% confidence interval: -5.17 to -0.06; P = 0.05), based on the decrease in the MLHFQ domain score. Marked statistical heterogeneity (I2> 70%) was observed for all the QOL and exercise capacity outcomes. CONCLUSIONS: Baduanjin exercise is a safe, feasible, and acceptable intervention that can improve the QOL and exercise capacity in patients with HF. However, more RCTs with rigorous research designs are needed to assist in the rehabilitation of such patients.

Folic acid attenuates chronic visceral pain by reducing clostridiales abundance and hydrogen sulfide production.

Irritable bowel syndrome (IBS) related chronic visceral pain affects 20% of people worldwide. The treatment options are very limited. Although the scholarly reviews have appraised the potential effects of the intestinal microbiota on intestinal motility and sensation, the exact mechanism of intestinal microbiota in IBS-like chronic visceral pain remains largely unclear. The purpose of this study is to investigate whether Folic Acid (FA) attenuated visceral pain and its possible mechanisms. Chronic visceral hyperalgesia was induced in rats by neonatal colonic inflammation (NCI). 16S rDNA analysis of fecal samples from human subjects and rats was performed. Patch clamp recording was used to determine synaptic transmission of colonic-related spinal dorsal horn. Alpha diversity of intestinal flora was increased in patients with IBS, as well as the obviously increased abundance of Clostridiales order (a main bacteria producing hydrogen sulfide). The hydrogen sulfide content was positive correlation with visceral pain score in patients with IBS. Consistently, NCI increased Clostridiales frequency and hydrogen sulfide content in feces of adult rats. Notably, the concentration of FA was markedly decreased in peripheral blood of IBS patients compared with non-IBS human subjects. FA supplement alleviated chronic visceral pain and normalized the Clostridiales frequency in NCI rats. In addition, FA supplement significantly reduced the frequency of sEPSCs of neurons in the spinal dorsal horn of NCI rats. Folic Acid treatment attenuated chronic visceral pain of NCI rats through reducing hydrogen sulfide production from Clostridiales in intestine.

Ethanol Extract of Glycyrrhiza uralensis Fisch: Antidiarrheal Activity in Mice and Contraction Effect in Isolated Rabbit Jejunum.

OBJECTIVE: To evaluate the antidiarrheal effect of ethanol extract of Glycyrrhiza uralensis Fisch root (GFR) in vivo and jejunal contraction in vitro. METHODS: In vivo, 50 mice were divided into negative control, positive control (verapamil), low-, medium- and high-dose GFR (250, 500, 1,000 mg/kg) groups by a random number table, 10 mice in each group. The antidiarrheal activity was evaluated in castor oil-induced diarrhea mice model by evacuation index (EI). In vitro, the effects of GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) on the spontaneous contraction of isolated smooth muscle of rabbit jejunum and contraction of pretreated by Acetylcholine (ACh, 10 µmol/L) and KCl (60 mmol/L) were observed for 200 s. In addition, CaCl2 was accumulated to further study its mechanism after pretreating jejunal smooth muscle with GFR (1 and 3 g/L) or verapamil (0.03 and 0.1 µmol/L) in a Ca2+-free-high-K+ solution containing ethylene diamine tetraacetic acid (EDTA). RESULTS: GFR (500 and 1,000 mg/kg) significantly reduced EI in castor oil-induced diarrhea model mice (P<0.01). Meanwhile, GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) inhibited the spontaneous contraction of rabbit jejunum (P<0.05 or P<0.01). Contraction of jejunums samples pretreated by ACh and KCl with 50% effective concentration (EC50) values was 1.05 (0.71-1.24), 0.34 (0.29-0.41) and 0.15 (0.11-0.20) g/L, respectively. In addition, GFR moved the concentration-effect curve of CaCl2 down to the right, showing a similar effect to verapamil. CONCLUSIONS: GFR can effectively against diarrhea and inhibit intestinal contraction, and these antidiarrheal effects may be based on blocking L-type Ca2+ channels and muscarinic receptors.

An ethyl acetate fraction of flavonoids from Polygonum hydropiper L. exhibits an anti-inflammatory activity in PCV2-infected porcine alveolar macrophages via PI3K/Akt and NF-κB pathways.

Porcine circovirus type 2 (PCV2) widely exists in swine production systems causing porcine circovirus diseases (PCVD) which is associated with significant economic losses. Polygonum hydropiper L. was used as a traditional Chinese medicine to treat a variety of diseases. This study was carried out to investigate anti-inflammatory activity of the ethyl acetate fraction of flavonoids from Polygonum hydropiper L. (FEA) in PCV2-induced porcine alveolar macrophages (3D4/2 cell line). The production of oxygen species (ROS) and the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-8 (IL-8) were detected to evaluate the anti-inflammatory activities of FEA. The translocation of nuclear factor-kappa B (NF-κB) and the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathways were investigated to document the potential anti-inflammatory mechanisms. In PCV2 induced 3D4/2 cells, FEA treatment significantly reduced the production of ROS, and sharply down-regulated the levels of TNF-α, IL-1ß and IL-8 in both secretion and mRNA expression level. The FEA also decreased the mRNA expression of Akt and NF-κB p65, reduced the transfer of p65 to nuclear, and inhibited the activation of PI3K/Akt signaling pathway. The findings suggest that FEA exhibited an anti-inflammatory activity in vitro and could be used as a candidate in treatment of inflammation induced by PCV2 infection.

The Gut Microbial Co-Abundance Gene Groups (CAGs) Differentially Respond to the Flavor (Yao-Wei) of Chinese Materia Medica.

The property theory is a unique principle instructing traditional Chinese doctors to prescribe proper medicines against diseases. As an essential part of it, the five-flavor theory catalogs various Chinese materia medicas (CMMs) into five flavors (sweet, bitter, sour, salty, and pungent) based on their taste and medical functions. Although CMM has been successfully applied in China for thousands of years, it is still a big challenge to interpret CMM flavor via modern biomarkers, further deepening its elusiveness. Herein, to identify the correlation between gut microbiota and CMM flavor, we selected 14 CMMs with different flavors to prepare their aqueous extracts, quantified the contained major chemical components, and then performed full-length 16S rRNA sequencing to analyze the gut microbiota of C57BL/6 mice administrated with CMM extracts. We found that flavones, alkaloids, and saponins were the richest components for sweet-, bitter-, and pungent-flavored CMMs, respectively. Medicines with merged flavors (bitter-pungent and sweet-pungent) displayed mixed profiles of components. According to gut microbial analysis, modulation of CMMs belonging to the same flavor on the taxonomic classification was inconsistent to an extent, while the functional sets of gut microbiota, co-abundance gene groups (CAGs), strongly and differentially responded to distinct flavors. Moreover, these correlations were in line with their pharmacological actions. Therefore, the gut microbial functional sets (CAGs) could act as the possible indicator to reflect CMM flavor, rather than the composition of microbial community.

Transcutaneous electrical nerve stimulation over acupoint for chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Background: Transcutaneous electrical nerve stimulation over an acupoint (acu-TENS), a new technique applied in pulmonary rehabilitation programs, has been gradually used in the management of chronic obstructive pulmonary disease (COPD). However, the effects of acu-TENS have not been fully evaluated. Therefore, this review was conducted to assess the effects of acu-TENS on COPD. Methods: A total of seven electronic databases were searched from their inception to September 2021 for randomized controlled trials of acu-TENS for COPD. Two investigators independently performed data extraction and methodological quality assessment. Heterogeneity was examined by Cochrane χ2 and I 2 tests. The source of heterogeneity was investigated by subgroup analysis or sensitivity analysis. Results: In our review, ten studies between 2008 and 2021 were included. The aggregated results indicated that acu-TENS showed positive effects in forced expiratory volume in 1 s (FEV1) [MD = 0.13 L, 95% CI (0.11-0.16), P < 0.00001], FEV1% predicted [MD = 5.92%, 95% CI (3.43-8.41), P < 0.00001], 6-min walk distance (6MWD) [MD = 14.68m, 95% CI (6.92-22.44), P = 0.0002], dyspnea visual analog scale (DVAS) [MD = -7.58, 95%CI (-14.33 to -0.84), P = 0.03], modified Borg scale (MBS) [MD = -0.46, 95% CI (-0.86 to -0.06), P = 0.03], and COPD assessment test (CAT) [MD = -4.25, 95% CI (-5.24 to -3.27), P < 0.00001]. Although six studies reported adverse effects, only one patient had shoulder pain after acu-TENS. Conclusion: Acu-TENS seems to be effective in improving pulmonary function and health status in patients with COPD, with little effect on exercise capacity and dyspnea. However, this result should be interpreted with caution, and high-quality RCTs were needed for further verification.

[Genetic diversity and population structure of germplasm resources of Amomum villosum based on SSR markers].

Amomum villosum, serving as an important medicinal material, is complex in the genetic background of germplasm resources. Exploring the genetic diversity and genetic relationship of germplasm resources is conducive to clarifying the germplasm source and genetic background of A. villosum, so as to improve the efficiency of parent selection and variety breeding of A. villosum. Seventy-one pairs of SSR primers were used for PCR amplification of 84 A. villosum samples by polyacrylamide gel electrophoresis. Fifty-four pairs of SSR primers with high polymorphism were screened out for the analysis of genetic diversity. The results showed that 293 alleles were detected from 84 germplasm resources by 54 pairs of SSR primers, with an average of 5.32 alleles for each pair of primers, and a variation range of 3-8, and the primer AVL12 marked the highest number of alleles. The PIC value of each locus varied from 0.068 7 to 0.828 9, with an average of 0.529 9, and the highest was marked by AVL24. The genetic diversity of A. villosum was the highest in Yunnan, followed by Guangxi, and the lowest was found in Guangdong. The population structure analysis and cluster analysis showed that the samples were classified into two groups. In terms of origin, samples from Yunnan and Guangxi had a close genetic relationship, and there was no obvious differentiation of A, villosum resources from different origins. In this study, 54 pairs of SSR markers were used to analyze the genetic diversity and population structure of 84 germplasm resources, which can reflect the genetic relationship between A. villosum samples from different germplasm sources and different populations, thus providing a theoretical basis for the collection, research, and breeding of A. villosum resources.

A novel iridoid glycoside leonuride (ajugol) attenuates airway inflammation and remodeling through inhibiting type-2 high cytokine/chemokine activity in OVA-induced asthmatic mice.

BACKGROUND: Asthma is a chronic airway disorder with a hallmark feature of airflow obstruction that associated with the remodeling and inflammation in the airway wall. Effective therapy for controlling both remodeling and inflammation is still urgently needed. Leonuride is the main pharmacological component identified from Bu-Shen-Yi-Qi-Tang (BSYQT) which has been traditionally used in treatment of lung diseases. However, no pharmacological effects of leonuride in asthma were reported. PURPOSE: Here we aimed to investigated whether leonuride provided a therapeutic efficacy in reversing asthma airway remodeling and inflammation and uncover the underlying mechanisms. STUDY DESIGN AND METHODS: Mouse models of chronic asthma were developed with ovalbumin (OVA) exposure for 8 weeks. Respiratory mechanics, lung histopathology and asthma-related cytokines were examined. Lung tissues were analyzed using RNA sequencing to reveal the transcriptional profiling changes. RESULTS: After oral administration with leonuride (15 mg/kg or 30 mg/kg), mice exhibited a lower airway hyperresponsiveness in comparison to asthmatic mice. Leonuride suppressed airway inflammation evidenced by the significant reductions in accumulation of inflammatory cells around bronchi and vessels, leukocyte population counts and the abundance of type 2 inflammatory mediators (OVA specific IgE, IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF). On the other hand, leonuride slowed down the process of active remodeling as demonstrated by weaker goblet cell metaplasia and subepithelial fibrosis in lung histopathology and lower transforming growth factor (TGF)-ß1 levels in serum and BALF in comparison to mice treated with OVA only. Furthermore, we uncovered transcriptional profiling alternations in lung tissue of mice after OVA exposure and leonuride treatment. Gene sets belonging to type-2 cytokine/chemokine activity stood out in leonuride target transcripts. Those upregulated (Bmp10, Ccl12, Ccl22, Ccl8, Ccl9, Cxcl15, Il13, Il33, Tnfrsf9, Il31ra, Il5ra, Il13ra2 and Ccl24) or downregulated (Acvr1c and Il18) genes in asthmatic mice, were all reversely regulated by leonuride treatment. CONCLUSIONS: Our results revealed the therapeutic efficacy of leonuride in experimental chronic asthma for the first time, and implied that its anti-inflammatory and antifibrotic properties might be mediated by regulation of type-2 high cytokine/chemokines responses.