Sanhuang Xiexin Decoction Ameliorates TNBC By Modulating JAK2-STAT3 and Lipid Metabolism.

OBJECTIVE: To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triple-negative breast cancer (TNBC) in mice and its underlying mechanism. METHODS: The high-performance liquid chromatography (HPLC) was used to quantitate and qualify SXD. A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×105 of 4T1-Luc cells to establish TNBC mouse model. All mice were divided randomly into 3 groups, including phosphate buffered solution (PBS), SXD and doxorubicin (DOX) groups (positive drug). Additionally, tumor growth, pathological changes, serum lipid profiles, expression of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway and its key targets including inflammatory factors, cell cycle and epithelial-mesenchymal transition (EMT) markers were investigated. Besides, the biosafety of SXD was also evaluated in mice. RESULTS: Rhein, coptisine, berberine hydrochloride and baicalin were all found in SXD, and the concentrations of these 4 components were 0.57, 2.61, 2.93, and 46.04 mg/g, respectively. The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells (P<0.01). The serum lipid analysis and Oil-Red-O staining both showed the differences, SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups (P<0.05 or P<0.01), respectively. SXD also decreased the levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3) expressions and its downstream factors, including mostly inflammatory cytokine, EMT markers, S phase of tumor cells and vascular endothelial growth factor (VEGF) expression (P<0.05 or P<0.01), respectively. The biosafety assessment of SXD revealed low levels of toxicity in mice. CONCLUSION: SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism.

Integrated network pharmacology and gut microbiome analysis to reveal the mechanism of Qu-Zhuo-Tong-Bi decoction against hyperuricemia and gout.

ETHNOPHARMACOLOGICAL RELEVANCE: Qu-zhuo-tong-bi decoction (QZTBD) is a classic Chinese herbal medicine that has shown therapeutic efficacy in clinical practice against hyperuricemia and gout. However, the potential mechanisms of QZTBD remain poorly investigated. AIM OF THE STUDY: To assess the therapeutic effects of QZTBD on hyperuricemia and gout and to reveal its mechanisms of action. MATERIALS AND METHODS: A Uox-KO mouse model of hyperuricemia and gout was established, and QZTBD was administered at a dosage of 18.0 g/kg/d. Throughout the experimental period, the effects of QZTBD on gout symptoms were monitored and analyzed. The integrated network pharmacology and gut microbiota analysis strategy was conducted to explore the mechanism of QZTBD in the treatment of hyperuricemia and gout. Targeted metabolomic analysis was performed to investigate the variation of amino acids and Spearman's rank correlation analysis was conducted to reveal the relationship between the discrepant bacterial genera and the altered amino acid. Flow cytometry was utilized to analysis the proportion of Th17 and Treg cells, and the production of pro-inflammatory cytokines was measured by ELISA. qRT-PCR and Western blot assay were applied to detect the expression of mRNA and protein respectively. Autodock vina 1.1.2 was used to evaluate the docking interactions. RESULTS: QZTBD treatment showed remarkable efficacy against hyperuricemia and gout with respect to attenuation of disease activity metrics through gut microbiome recovery and intestinal immune homeostasis. The administration of QZTBD significantly elevated the abundance of Allobaculum and Candidatus sacchairmonas, corrected the aberrant amino acid patterns, repaired the impaired intestinal barrier, restored the balance of Th17/Treg cells via PI3K-AKT-mTOR pathway, and reduced the levels of inflammatory cytokines such as IL-1ß, IL-6, TNF-α and IL-17. Fecal microbiota transplantation from QZTBD treated mice demonstrated convincing evidence of efficacy and mechanism of QZTBD. CONCLUSION: Taken together, our study explores the therapeutic mechanism of an effective herbal formula, QZTBD, for gout treatment through remodeling gut microbiome and regulating the differentiation of CD4+ T cells via PI3K-AKT-mTOR pathway.

Jieduquyuziyin prescription alleviates SLE complicated by atherosclerosis via promoting cholesterol efflux and suppressing TLR9/MyD88 activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Jieduquyuziyin prescription (JP), as a traditional Chinese medicine formula, is extensively applied to treat systemic lupus erythematosus (SLE). Its prescription is based on clinical practice and an evidence-based application of traditional medicines. It is approved by use in Chinese hospitals as a clinical prescription that can be directly used. AIM OF THE STUDY: The study aims to elucidate JP's efficacy on lupus-like disease combined with atherosclerosis and to explore its mechanism. MATERIALS AND METHODS: To conduct in vivo experiments, we established a model of lupus-like disease with atherosclerosis in ApoE-/- mice fed a high-fat diet and injected intraperitoneally with pristane. In addition, oxidized low-density lipoprotein (ox-LDL) and a TLR9 agonist (CpG-ODN2395) were utilized to examine the mechanism of JP on SLE combined with AS in RAW264.7 macrophages in vitro. RESULTS: Results indicated that JP reduced hair loss and levels of the spleen index, maintained stable body weight, alleviated kidney damage in mice, and reduced the expression levels of urinary protein, autoantibodies, and inflammatory factors in serum. Furthermore, JP is effective at alleviating the lupus-like symptoms observed in mice. In mice, JP inhibited aortic plaque deposition, stimulated lipid metabolism, and increased the expression of genes that regulate cholesterol efflux, including ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette subfamily G member 1 (ABCG1), scavenger receptor class B type I (SR-BI), and peroxisome proliferator-activated receptor γ (PPAR-γ). In vivo, JP inhibited the expression of the Toll-like receptor 9 (TLR9)-induced signaling pathway, which links TLR9/MyD88/NF-kB to the expression of subsequent inflammatory factors. Furthermore, JP inhibited the expression of TLR9 and MyD88 in vitro. In addition, the JP treatment effectively reduced foam cell formation in RAW264.7 macrophages by increasing the expression of ABCA1/G1, PPAR-γ and SR-BI. CONCLUSIONS: JP played a therapeutic role in ApoE-/- mice with pristane-induced lupus-like diseases and AS, possibly through inhibition of TLR9/MyD88 signaling and promotion of cholesterol efflux.

Positive effects of Mulberry leaf extract on egg quality, lipid metabolism, serum biochemistry, and antioxidant indices of laying hens.

Plant extracts are becoming a hot topic of research by animal husbandry practitioners following the implementation of a global policy to restrict antibiotic use in animal production. Mulberry leaf extract has received considerable attention as a new plant extract. Mulberry leaf polysaccharides and flavonoids are its main constituents, and these substances possess immunoregulatory, hypoglycemic, antioxidant, and anticoagulant properties. It is however less common to use them in poultry production. Therefore, we investigated the effects of adding MLE to the diet of laying hens on egg quality, lipid metabolism, serum biochemistry, and antioxidant indices in this study. A total of 288 Lohmann Silber layers, aged 38 weeks, were randomly assigned to four groups (six replicates of 12 hens each). Hens were fed a basal diet supplemented with 0 (control diet), 0.4, 0.8, or 1.2% MLE for 56 d. Results showed that the addition of 0.4-1.2% MLE to the diet improved aspartate transaminase (AST) activity in the serum of laying hens, reduced low-density lipoprotein (LDL-C) content in the serum, and significantly decreased yolk triglyceride (TG) and total cholesterol (TC) contents (P < 0.05). No adverse effects were observed on production performance (P > 0.10). MLE (0.4 and 1.2%) significantly reduced the TG and TC levels in the liver (P < 0.05). MLE (0.8 and 1.2%) significantly increased glutathione peroxidase (GSH-Px) activity in the serum, decreased alanine transaminase (ALT) activity, TG and TC content in the serum, and improved egg yolk color (P < 0.05). MLE (1.2%) significantly increased high-density lipoprotein (HDL-C) content and superoxide dismutase (SOD) activity in the serum and enhanced eggshell strength (P < 0.05). The liver-related lipid metabolism gene assay revealed that the relative mRNA expression of PPARα and SIRT1 in the liver was significantly upregulated and that of FASN and PPARγ was significantly decreased after the addition of MLE. In contrast, the relative mRNA expression of SREBP-1c in the liver dramatically decreased after the addition of 0.8 and 1.2% MLE (P < 0.05). The addition of MLE to the diet improved egg quality and the economic value of hens by increasing antioxidant capacity and lipid metabolism. The most appropriate amount of MLE to be added to the diet of laying hens was 0.8%. Our study provides a theoretical reference for the application of MLE in egg production and to promote the healthy and sustainable development of the livestock and poultry industry under the background of antibiotic prohibition.

Jieduquyuziyin prescription promotes the efficacy of prednisone via upregulating Nrf2 in MRL/lpr kidneys.

ETHNOPHARMACOLOGICAL RELEVANCE: The Jieduquyuziyin prescription (JP), a traditional Chinese medicine (TCM) formula, has been used as an approved hospital prescription to improve the efficacy of prednisone (Pred) in systemic lupus erythematosus (SLE) and lupus nephritis (LN) treatment. Although the synergistic effect of JP and Pred is prominent, the underlying mechanisms require further investigation. AIM OF THE STUDY: To explore the key therapeutic targets of JP in improving the role of Pred in the treatment of LN. MATERIALS AND METHODS: Lupus-prone female MRL/lpr mice were administered JP, Pred, or JP combined with Pred. The effect of JP on LN was estimated by evaluating renal function and inflammation levels in the kidneys. On this basis, RNA sequencing of kidney tissues was performed, and the differentially expressed genes were analyzed and summarized. The role of JP in the expression of nuclear factor erythroid 2-related factor 2 (NFE2L2 or Nrf2) in the kidneys was further confirmed by real-time PCR, immunohistochemistry, and western blotting. RESULTS: JP combined with Pred exhibited the most remarkable therapeutic effect compared with JP or Pred alone. Transcriptome analysis indicated that Nrf2, a central mediator of the antioxidative response, was significantly upregulated by JP. Based on these results, we speculated that Nrf2 is a critical factor for JP, improving the efficacy of Pred in treating LN by notably suppressing the oxidative stress level in the kidneys. Furthermore, we found that Nrf2 expression decreased with the exacerbation of LN in MRL/lpr mice. In addition, the downregulated Nrf2 was notably restored after JP treatment, accompanied by suppressed oxidative stress levels in the kidneys. It includes inhibited accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), restored mitochondrial membrane potential (MMP) levels, and increased antioxidant enzyme activity of superoxide dismutase (SOD). CONCLUSIONS: Our findings show that JP increases Pred efficacy by increasing Nrf2 expression, implying that Nrf2 may be a promising therapeutic target for the treatment of LN.

Anticancer effects of herbal medicines in pancreatic ductal adenocarcinoma through modulation of steroid hormone response proteins.

Many individual herbs and herbal formulae have been demonstrated to provide safe and effective treatment for pancreatic ductal adenocarcinoma (PDAC); however, the therapeutic mechanisms underlying their effects have not been fully elucidated. A total of 114 herbal formulae comprising 216 single herbal medicines used to treat PDAC were identified. Cluster analysis revealed a core prescription including four herbs [Glycyrrhizae Radix et Rhizome (Gan Cao), Codonopsis Radix (Dang Shen), Citri Reticulatae Pericarpium (Chen Pi), and Pinelliae Rhizoma (Ban Xia)] in combination to treat PDAC, and 295, 256, 141, and 365 potential targets were screened for each of these four herbs, respectively. PDAC-related proteins (n = 2940) were identified from the DisGeNET database. Finally, 44 overlapping targets of herbs and PDAC were obtained, representing potential targets of the herbal medicines for PDAC treatment. GO enrichment analysis indicated that targets common to herbs and PDAC primarily functioned in response to steroid hormones. KEGG pathway enrichment analysis indicated that the herbs may prevent PDAC by influencing apoptotic, p53, and PI3K/Akt signaling pathways. Further, molecular docking analysis indicated that of identified bioactive compounds, stigmasterol, phaseol, perlolyrine, shinpterocarpin, and licopyranocoumarin have good binding ability with proteins involved in responses to steroid hormones, while stigmasterol, phaseol, perlolyrine, and DIOP have good binding ability with PTGS2(also known as COX-2), ESR1, ESR2, AR, and PGR. The anti-PDAC activity of herbal medicines may be mediated via regulation of proteins with roles in responses to steroid hormones. This study provides further evidence supporting the potential for use of herbal medicines to treat PDAC.

Acupotomy Contributes to Suppressing Subchondral Bone Resorption in KOA Rabbits by Regulating the OPG/RANKL Signaling Pathway.

Subchondral bone lesions, as the crucial inducement for accelerating cartilage degeneration, have been considered as the initiating factor and the potential therapeutic target of knee osteoarthritis (KOA). Acupotomy, the biomechanical therapy guided by traditional Chinese meridians theory, alleviates cartilage deterioration by correcting abnormal mechanics. Whether this mechanical effect of acupotomy inhibits KOA subchondral bone lesions is indistinct. This study aimed to investigate the effects of acupotomy on inhibiting subchondral bone resorption and to define the possible mechanism in immobilization-induced KOA rabbits. After KOA modeling, 8 groups of rabbits (4w/6w acupotomy, 4w/6w electroacupuncture, 4w/6w model, and 4w/6w control groups) received the indicated intervention for 3 weeks. Histological and bone histomorphometry analyses revealed that acupotomy prevented both cartilage surface erosion and subchondral bone loss. Further, acupotomy suppressed osteoclast activity and enhanced osteoblast activity in KOA subchondral bone, showing a significantly decreased expression of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinases-9 (MMP-9), and cathepsin K (Ctsk) and a significantly increased expression of osteocalcin (OCN); this regulation may be mediated by blocking the decrease in osteoprotegerin (OPG) and the increase in NF-κB receptor activated protein ligand (RANKL). These findings indicated that acupotomy inhibited osteoclast activity and promoted osteoblast activity to ameliorate hyperactive subchondral bone resorption and cartilage degeneration in immobilization-induced KOA rabbits, which may be mediated by the OPG/RANKL signaling pathway. Taken together, our results indicate that acupotomy may have therapeutic potential in KOA by restoring the balance between bone formation and bone resorption to attenuate subchondral bone lesions.

Halobaculum halophilum sp. nov. and Halobaculum salinum sp. nov., isolated from salt lake and saline soil.

Two halophilic archaeal strains, Gai3-2T and NJ-3-1T, were isolated from salt lake and saline soil samples, respectively, collected in PR China. The 16S rRNA gene sequences of the two strains were 97.5% similar to each other. Strains Gai3-2T and NJ-3-1T had the highest sequence similarities to 'Halobonum tyrrellense' G22 (96.7 and 97.8%, respectively), and displayed similarities of 91.5-93.5% and 92.3-94.7%, respectively, to Halobaculum members. Phylogenetic analysis revealed that the two strains formed different branches and clustered tightly with 'H. tyrrellense' G22 and Halobaculum members. The average nucleotide identity (ANI), in silico DNA-DNA hybridization (isDDH) and amino acid identity (AAI) values between the two strains were 83.1, 26.9 and 77.9%, respectively, much lower than the threshold values proposed as a species boundary. These values between the two strains and 'H. tyrrellense' G22 (ANI 77.9-78.2%, isDDH 22.5-22.6% and AAI 68.8-69.3%) and Halobaculum members (ANI 77.53-77.63%, isDDH 21.8-22.3% and AAI 68.4-69.4%) were almost identical, and much lower than the recommended threshold values for species delimitation. These results suggested that strains Gai3-2T and NJ-3-1T represent two novel species of Halobaculum. Based on phenotypic, chemotaxonomic and phylogenetic properties, strains Gai3-2T (=CGMCC 1.16080T=JCM 33550T) and NJ-3-1T (=CGMCC 1.16040T=JCM 33552T) represent two novel species of the genus Halobaculum, for which the name Halobaculum halophilum sp. nov. and Halobaculum salinum sp. nov. are proposed.

Successful treatment of acute promyelocytic leukemia in a 92-year-old man using all-trans retinoic acid combined with oral arsenic: A case report.

RATIONALE: Acute promyelocytic leukemia is a special subtype of acute myeloid leukemia. The incidence of early death and complications is high. An oral regimen of all-trans retinoic acid combined with the realgar-indigo naturalis formula (RIF) without chemotherapy has provided a new strategy for the treatment of these patients. PATIENT CONCERNS: A 92-year-old male patient was admitted to the hospital due to fatigue and oral bleeding. He had no fever or lung infection. Routine blood test showed white blood cell count 1.0 ×109/L, hemoglobin 100 g/L, and platelets 21 × 109/L. Coagulation function indicated fibrinogen 1.02 g/L and D-dimer 2360 ng/mL. And 28% abnormal promyelocytes were observed in peripheral blood. DIAGNOSIS: A bone marrow morphologic, immunophenotypic, cytogenetic, and molecular examination was performed. Routine bone marrow examination showed active proliferation of nucleated cells, with promyelocytes accounting for 91%; immunophenotyping revealed an early myeloid cell population, accounting for approximately 82.4% of all cells. INTERVENTIONS: From February 15, 2020, 25 mg/m2 all-trans retinoic acid was orally administered daily. After the fusion gene result was obtained, oral administration of 60 mg/kg RIF daily began since February 18, 2020. The combination of the 2 agents was given until March 16, 2020. Oral administration of 25 mg/m2 retinoic acid daily began from March 20, 2020 for 2 weeks, and oral administration of 60 mg/kg RIF daily lasted for 4 weeks as the consolidation therapy. During the treatment, the proportion of promyelocytes in peripheral blood, white blood cell count, platelets, coagulation function, liver function, and QT interval were monitored. OUTCOMES: Oral retinoic acid and oral RIF were given without chemotherapy and the patient achieved bone marrow remission after 1 month, and molecular remission was achieved 2 months later. In the early stage of acute promyelocytic leukemia, combined thrombocytopenia and disseminated intravascular coagulation may develop. Platelet and fresh frozen plasma infusion were proactively given until platelets were stabilized above 30 × 109/L, and the coagulation function returned to normal. LESSONS: The regimen was safe and effective, and subsequent treatment did not require hospitalization, which helped to improve the patient's quality of life.

Network analysis indicating the pharmacological mechanism of Yunpi-Qufeng-Chushi-prescription in prophylactic treatment of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA), is an autoimmune inflammatory disease with increasing global morbidity and high disability. Early treatment is an effective intervention to slow down joint deformation. However, as for early RA and pre-RA patients, it sometimes takes a long time to make a definite diagnosis and few guidelines have made suggestion for these suspected or early phrase individuals. Yunpi-Qufeng-Chushi-Prescription (YQCP) is an optimization of the traditional formula, Cangzhu Fangfeng Tang which is effective for arthromyodynia management. METHODS: In this study, LC-MS identify the main component of YQCP. Ingredients of the 11 herbs were collected from Traditional Chinese Medicine Integrated Database (TCMID). Targets of these ingredients were collected from two source, TCMID and PharmMapper. Microarray of 20 early untreated RA patients and corresponding health control were download from NCBI Gene Expression Omnibus (GEO) database to defined the differential expressed genes. Gene ontology analysis and KEGG enrichment analysis were carried out for the YQCP. Protein-protein interactions (PPIs) networks were constructed to identify the hub targets. At last, molecular docking (MD) were conducted to further verified the the possibility of YQCP for RA therapy. RESULT: The study indicated that by acting on hub targets such as C3, EGFR, SRC and MMP9, YQCP may influence the mature of B cells and inhibit B cell-related IgG production, regulate oxidative stress and modulate activity of several enzymes including peroxidase and metallopeptidase to delay the occurrence and progress of RA and benefit the pre-RA or early RA patients. CONCLUSION: YQCP is a potential effective therapy for prophylactic treatment of RA.

A meta-analysis of the clinical efficacy of Tanreqing injection combined with antibiotics vs antibiotics alone for treating pulmonary infection secondary to intracerebral hemorrhage.

BACKGROUND: Pulmonary infection is the most common complication to develop after intracerebral hemorrhage (ICH). Antibiotics have certain limitations when used to treat pulmonary infection, while Tanreqing injection (TRQI) is extensively used to treat pulmonary infection as an adjuvant to antibiotics. The aim of this meta-analysis was to investigate the clinical efficacy of TRQI for the treatment of lung infection secondary to ICH. METHODS: Randomized controlled trials (RCTs) assessing the combination of TRQI and antibiotics compared to antibiotics alone for pulmonary infection after ICH were comprehensively searched for in 7 electronic databases from their establishment to August 2020. Two independent researchers conducted the literature retrieval, screening, and data extraction. The assessment tool of Cochrane risk of bias and Review Manager 5.3 software were applied to assess the methodological quality and analyze the data, respectively. RESULTS: Seventeen RCTs involving 1122 patients with pulmonary infection after ICH were included. Compared to antibiotics alone, the combination treatment enhanced the clinical effective rate, shortened the hospital stay, reduced the white blood cell, procalcitonin, and C-reactive protein levels, ameliorated the times to the resolution of fever, cough, and lung rales, and increased the oxygenation index. The evidence indicated that TRQI combined with antibiotics caused no adverse reactions. CONCLUSIONS: Our study showed that the combination of TRQI and antibiotics was effective for treating pulmonary infection after ICH. However, high-quality multicenter RCTs are needed to further verify the clinical efficacy of TRQI due to the publication bias and the low methodological quality of the included RCTs.

A comparison of the effects of Chinese non-pharmaceutical therapies for pain control in knee osteoarthritis: A protocol for a systematic review and network meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic degenerative joint disease, leading to pain and functional limitation in the elderly. The non-pharmaceutical therapy is recommended firstly by different guidelines for KOA management strategies. In China, there are various forms of non-pharmaceutical treatments for KOA, which are considered beneficial in relieving KOA pain. However, there is no consensus on which is the optimal non-pharmaceutical regimens. Thus, present network meta-analysis aims to assess the comparative efficacy of available Chinese non-pharmaceutical therapies, especially in pain management. METHODS: PubMed, EMBASE, Cochrane library, Web of Science, China national knowledge infrastructure, VIP, Wan Fang will be systematically searched their inception to April 2020. Randomized controlled trials that compared the effect of non-pharmaceutical therapies on pain control in KOA will be included, including traditional acupuncture, electroacupuncture, warming needle, fired needle, acupuncture followed by moxibustion, moxibustion and massage. The primary outcome was the knee pain levels, and secondary outcome was the comprehensive indicators. Risk of bias assessment of the included studies will be performed according to the Cochrane risk of bias tool. The pairwise and network meta-analysis will be performed by STATA 14.0 and GeMTC softwares. RESULTS: This study is ongoing and will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide a comprehensive evidence on the effects of Chinese non-pharmaceutical therapies for pain control in KOA. PROSPERO REGISTRATION NUMBER: CRD42018106575.

A comparison of the effects of electroacupuncture versus transcutaneous electrical nerve stimulation for pain control in knee osteoarthritis: a Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: To compare the effectiveness of electroacupuncture (EA) and transcutaneous electrical nerve stimulation (TENS) for pain control in knee osteoarthritis (KOA). METHODS: Four English (MEDLINE, EMBASE, Cochrane Library and Web of Science) and three Chinese (China Science Journal Citation Report (VIP), Wanfang and China National Knowledge Infrastructure (CNKI)) language databases were searched for eligible randomized controlled trials (RCTs), comparing four approaches: EA, TENS, medication and sham/placebo controls. The primary outcome was pain intensity, measured by visual analogue scale (VAS), numeric-rating scale (NRS) or Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale. Classic pairwise and Bayesian network meta-analyses were conducted to integrate the treatment efficacy/effectiveness through direct and indirect evidence. RESULTS: Thirteen studies were included. In the direct meta-analyses, there was no statistically significant overall effect of EA (mean difference (MD) -4.77, 95% confidence interval (CI) -12.51 to 2.96), while the overall effects of high-frequency transcutaneous electrical nerve stimulation (H-TENS) (MD -16.63, 95% CI -24.57 to -8.69) and medication (MD -7.12, 95% CI -12.07 to -2.17) were statistically significant. In the network meta-analyses, the relative effect of the EA and H-TENS groups (MD 5.07, 95% CI -11.33 to 21.93) on pain control did not differ. Meanwhile, H-TENS demonstrated the highest probability of being the first best treatment, and EA had the second highest probability. CONCLUSION: The present analysis indicated that both EA and TENS exert significant pain relieving effects in KOA. Among the four treatments, H-TENS was found to be the optimal treatment choice for the management of KOA pain in the short-term, and EA the second best treatment option. Given that the application of TENS is recommended by various international guidelines for the treatment of KOA, EA may also represent a potentially effective non-pharmacologic therapy.

In Vitro Evaluation of the Neuroprotective Effect of Panax notoginseng Saponins by Activating the EGFR/PI3K/AKT Pathway.

OBJECTIVE: This study investigated whether Panax notoginseng saponins (PNS) extracted from Panax notoginseng (Bruk.) F. H. Chen played a neuroprotective role by affecting the EGFR/PI3K/AKT pathway in oxygen-glucose deprived (OGD) SH-SY5Y cells. MATERIALS AND METHODS: Different groups of OGD SH-SY5Y cells were treated with varying doses of PNS, PNS + AG1478 (a specific inhibitor of EGFR), or AG1478 for 16 hours. CCK8, Annexin V-FITC/PI apoptosis analysis, and LDH release analysis were used to determine cell viability, apoptosis rate, and amounts of LDH. Quantitative real-time PCR (q-RT-PCR) and western blotting were used to measure mRNA and proteins levels of p-EGFR/EGFR, p-PI3K/PI3K, and p-AKT/AKT in SH-SY5Y cells subjected to OGD. RESULTS: PNS significantly enhanced cell viability, reduced apoptosis, and weakened cytotoxicity by inhibiting the release of LDH. The mRNA expression profiles of EGFR, PI3K, and AKT showed no difference between model and other groups. Additionally, ratios of p-EGFR, p-PI3K, and p-AKT to EGFR, PI3K, and AKT proteins expression, respectively, all increased significantly. CONCLUSIONS: These findings indicate that PNS enhanced neuroprotective effects by activating the EGFR/PI3K/AKT pathway and elevating phosphorylation levels in OGD SH-SY5Y cells.

Electroacupuncture alleviates cartilage degradation: Improvement in cartilage biomechanics via pain relief and potentiation of muscle function in a rabbit model of knee osteoarthritis.

Knee osteoarthritis (KOA) is a chronic degenerative joint disorder characterized by loss of articular cartilage and progressive deterioration, leading to pain and functional limitation. Abnormal biomechanics play a core role in the onset and development of KOA. The aim of this study was to explore whether electroacupuncture (EA) may relieve pain and adjust the biomechanical properties of the extensor-flexor muscles to improve abnormal joint loading, thus alleviating the degradation of cartilage in a rabbit model of KOA. Firstly, a KOA model was induced by immobilization for 6 weeks. Then, different interventions (EA and celecoxib) were applied for 4 weeks. The levels of pain and disability were assessed using the Lequesne MG index. Muscle function, including function of the rectus femoris and biceps femoris, was tested through hematoxylin-eosin staining (HE staining) and use of a microforce tension-torsion instrument. The cartilage was tested using nanoindentation, Safranin O-Fast Green staining, confocal laser scanning microscopy (immunofluorescence), immunohistochemistry and the enzyme-linked immunosorbent assay (ELISA). Finally, we found that EA and celecoxib resulted in lower behavioral and pain scores than the model group. In addition, it improved the function of muscles. Furthermore, those treatments alleviated the rate of cartilage degradation, manifested as increased loss factor without statistical difference and a significant reduction in the Mankin score. This promoted the metabolism of type II collagen in the cartilage layer and drastically reduced the expression of CTX-II in the synovial fluid and peripheral serum. Concisely, EA promotes pain limitation and ameliorates muscular atrophy-induced inappropriate biomechanical loading on the articular cartilage through pain relief and potentiation of muscle function, thus improving cartilage viscoelasticity, as demonstrated by the retarded degradation of type II collagen in our KOA model.

Qu-Zhuo-Tong-Bi Decoction Alleviates Gouty Arthritis by Regulating Butyrate-Producing Bacteria in Mice.

Qu-zhuo-tong-bi decoction (QZTBD) is a traditional Chinese medicine prescription used to treat hyperuricemia and gout with no obvious adverse effects. However, the mechanism by which QZTBD treats gout has not been fully explored. Here, we investigated the effects of QZTBD on gouty arthritis and its therapeutic mechanism from the perspective of the gut microbiome. Our results demonstrated that QZTBD was effective for reducing serum uric acid level and attenuating paw edema and mechanical allodynia. QZTBD promoted the abundance of butyrate-producing bacteria and the production of SCFAs. Further study revealed that QZTBD restored the intestinal barrier function, modulated the expression of GPR43 and ABCG2, suppressed the activity of key glycolysis-related enzymes, and inhibited the generation of intestinal inflammatory factors. These findings suggested that QZTBD is an effective therapeutic drug for gouty arthritis. Butyrate-producing bacteria and its metabolites SCFAs might act as a potential target of QZTBD.

Non-targeted metabolomics reveals diagnostic biomarker in the tongue coating of patients with chronic gastritis.

Analysis of the properties of the tongue has been used in traditional Chinese medicine for disease diagnosis. Notably, tongue analysis, which is non-invasive and convenient compared with gastroscopy and pathological examination, can be used to assess chronic gastritis (CG). In order to find potential diagnostic biomarkers and study the metabolic mechanisms of the endogenous small molecules in the tongue coating related to CG, a non-targeted metabolomic analysis method was developed using ultra high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS). It was performed using two different columns in positive and negative ion scanning modes separately. The stability of the samples was evaluated and the age and gender factors of the subjects were excluded to ensure the reliability of the data in this study. Finally, under the four analysis models, 130, 229, 113 and 92 differential compounds were found using multivariate statistical methods respectively. 37 potential biomarkers were putatively identified after removing the duplicate compounds and five potential diagnostic biomarkers were putatively identified by receiver operating characteristic (ROC) curve analysis, including inosine, oleamide, adenosine, N-acetylglucosamine (GlcNAc) and xanthine. The main metabolic pathways associated with CG were purine metabolism, amino acid metabolism, sphingolipid metabolism and energy metabolism, which suggested that oxygen free radicals and energy metabolism were altered in patients with CG. These results provided a potential new basis for the quantitative diagnosis and pathogenesis of CG.

A comparison of the effects of electroacupuncture vs transcutaneous electrical nerve stimulation for pain control in knee osteoarthritis: A protocol for network meta-analysis of randomized controlled trials.

BACKGROUND: Knee osteoarthritis (KOA), the most common type of osteoarthritis, is a chronic degenerative joint disease accompanied by pain and functional limitation for the elderly. The 2 nonpharmacologic approaches, electroacupuncture (EA) and transcutaneous electrical nerve stimulation (TENS), are considered beneficial in relieving KOA pain, however, the current conclusions are controversial. Furthermore, no direct or indirect meta-analyses between EA and TENS have been reported for the pain relief of KOA patients. METHODS: PubMed, EMBASE, Cochrane library, Web of Science, CNKI, VIP, Wan Fang will be systematically searched their inception to May 2018. Randomized controlled trials that compared the effect of EA and TENS on pain control in knee osteoarthritis will be included. The primary outcome was the knee pain levels, and secondary outcome was the comprehensive indicators. Risk of bias assessment of the included studies will be performed according to the Cochrane risk of bias tool. The pairwise and network meta-analysis will be performed by STATA 14.0 software. RESULTS: This study is ongoing and will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide comprehensive evidence on the effects of EA and TENS for pain control in knee osteoarthritis. PROSPERO REGISTRATION NUMBER: CRD42018091826.

[Effect of needle knife intervention on tensile mechanics of femoral quadriceps tendon in rabbits with knee osteoarthritis].

OBJECTIVE: To observe the effects of acupotomy intervention on the behavior, morphology and tensile mechanics of knee osteoarthritis (KOA) rabbits, and to explore the biomechanical effects of acupotomy on KOA. METHODS: Twenty-four New Zealand male rabbits were randomly divided into four groups: normal group, model group, electroacupuncture group and needle-knife group, with 6 rabbits in each group. In each model group, rabbit KOA model was established by fixing Videman's left hind limb in straight position for 6 weeks. In the electroacupuncture group, rats were treated left on Liang Qiu, Xue Hai, Nei Xi Yan and Wai Xi Yan 3 times a week for 3 weeks. In the acupotomology group, the left quadriceps femoris tendon was released with acupotomology, and the treatment was once a week for 3 weeks. Behavioral tests were performed using Lequesne MG knee joint evaluation method one week after the end of modeling and one week after the end of treatment, and HE staining and mechanical tests were performed one week after the end of treatment. RESULTS: Behavioral observation before treatment showed that there were significant differences in local pain, gait response, joint activity and joint swelling between the normal group and the model group(P<0.05), while there was no significant difference among the model group, electro-acupuncture group and needle-knife group(P>0.05). After treatment, the results showed that there were significant differences in local pain, gait response, joint activity and joint swelling among model group, electro-acupuncture group and needle-knife group compared with normal group(P<0.05); In local pain, the electro-acupuncture group was lower than the model group, and there was no significant difference(P>0.05); there was significant difference between needle knife group and model group(P<0.05); there was no significant difference between electro-acupuncture group and needle-knife group(P>0.05). In gait change, there was significant difference between model group and electro-acupuncture group(P<0.05); there was no significant difference between needle-knife group and model group(P>0.05). In joint activity, there was significant difference between electro-acupuncture group and model group(P<0.05). In joint swelling, compared with model group, there was significant difference on electro-acupuncture group and electro-knife group(P<0.01), but there was no significant difference between the electro-acupuncture group and the needle-knife group(P>0.05). Mechanics: Compared with the blank group, the ultimate load of the model group decreased significantly(P<0.01), the ultimate load of the electro-acupuncture group decreased(P>0.05), and the ultimate load of the needle-knife group increased(P>0.05). Compared with the model group, the ultimate load of the electro-acupuncture group increased significantly(P<0.05), and the ultimate load of the needle-knife group increased significantly (P<0.01). Compared with the electro-acupuncture group, the ultimate load of the needle-knife group increased(P>0.05). Compared with the blank group, the maximum displacement of the model group decreased significantly(P<0.01), and the maximum displacement of the electro-acupuncture group and the needle-knife group decreased(P>0.05). Compared with the model group, the maximum displacement of the electro-acupuncture group increased(P>0.05), and the maximum displacement of the needle-knife group increased significantly(P<0.05). Compared with the electro-acupuncture group, the maximum displacement of the needle-knife group increased(P>0.05). There was no significant difference in stiffness among groups(P>0.05). CONCLUSIONS: Acupotomy intervention can significantly change the behavior and morphology, significantly improve the mechanical properties of quadriceps femoris tendon stretch, and exert its biomechanical effects to achieve the purpose of treating KOA.

Anti-proliferative and anti-migratory effects of Scutellaria strigillosa Hemsley extracts against vascular smooth muscle cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The abnormal increase in vascular smooth muscle cell (VSMC) proliferation and migration are critical events in the pathogenesis of cardiovascular diseases (CVDs) including restenosis and atherosclerosis. The dried roots of Scutellaria baicalensis Georgi (common name: Huangqin in China) have been confirmed to possess beneficial effects on CVD by clinical and modern pharmacological studies. Flavonoids in Huangqin exert anti-proliferative and anti-migratory effects. Similar to Huangqin, Scutellaria strigillosa Hemsley (SSH) has been used to clear heat and damp and is especially rich in flavonoids including wogonin, wogonoside, baicalein, and baicalin. However, there have been few of reports about pharmacological activities of SSH. AIM OF THE STUDY: To investigate the anti-proliferative and anti-migratory properties of Scutellaria strigillosa Hemsley extract (SSHE) in vitro and in vivo and explore its possible mechanism of action. MATERIALS AND METHODS: The chemical constituents of SSHE were analyzed by ultra-high performance liquid chromatography coupled with triple time-of-flight mass spectrometry (UPLC-Triple-TOF-MS/MS). Cell proliferation and migration were investigated using BrdU incorporation assay and cell scratch test, respectively. The protein expression was determined by western blotting. In vivo, we established an artery ligation model of C57BL/6 mice and orally administered them with 50 or 100 mg/kg/day of SSHE. The carotid arteries were harvested and the intima-media thickness was examined 28 days post-ligation. RESULTS: Twelve compounds were identified and tentatively characterized. SSHE significantly inhibited the VSMC proliferation and migration stimulated by PDGF-BB and decreased the relative protein expression of regulatory signaling intermediates. Furthermore, the expression of SM22α was significantly elevated in SSHE-pretreated VSMCs, whereas knockdown of SM22α impaired the PDGF-BB-induced proliferation and migration arrest. Meanwhile, both ROS generation and the phosphorylation of ERK decreased in SSHE-pretreated VSMCs. In carotid artery ligation mice model, SSHE treatment significantly inhibited neointimal hyperplasia. CONCLUSIONS: SSHE significantly inhibited the PDGF-BB-induced VSMC proliferation, migration, and neointimal hyperplasia of carotid artery caused by ligation. Upregulation of SM22α expression, inhibition of ROS generation and ERK phosphorylation were, at least, partly responsible for the effects of SSHE on VSMCs.