Engineering a hyaluronic acid-encapsulated tumor-targeted nanoplatform with sensitized chemotherapy and a photothermal effect for enhancing tumor therapy.

Chemotherapy remains one of the most widely used cancer treatment modalities in clinical practice. However, the characteristic microenvironment of solid tumors severely limits the anticancer efficacy of chemotherapy. In addition, a single treatment modality or one death pathway reduces the antitumor outcome. Herein, tumor-targeting O2 self-supplied nanomodules (CuS@DOX/CaO2-HA) are proposed that not only alleviate tumor microenvironmental hypoxia to promote the accumulation of chemotherapeutic drugs in tumors but also exert photothermal effects to boost drug release, penetration and combination therapy. CuS@DOX/CaO2-HA consists of copper sulfide (CuS)-loaded calcium peroxide (CaO2) and doxorubicin (DOX), and its surface is further modified with HA. CuS@DOX/CaO2-HA underwent photothermal treatment to release DOX and CaO2. Hyperthermia accelerates drug penetration to enhance chemotherapeutic efficacy. The exposed CaO2 reacts with water to produce Ca2+, H2O2 and O2, which sensitizes cells to chemotherapy through mitochondrial damage caused by calcium overload and a reduction in drug efflux via the alleviation of hypoxia. Moreover, under near infrared (NIR) irradiation, CuS@DOX/CaO2-HA initiates a pyroptosis-like cell death process in addition to apoptosis. In vivo, CuS@DOX/CaO2-HA demonstrated high-performance antitumor effects. This study provides a new strategy for synergistic enhancement of chemotherapy in hypoxic tumor therapy via combination therapy and multiple death pathways.

The construction of hierarchical assemblies with in situ generation of chemotherapy drugs to enhance the efficacy of chemodynamic therapy for multi-modal anti-tumor treatments.

The effectiveness of chemodynamic therapy (CDT) in cancer treatment is limited by insufficient endogenous H2O2 levels in tumor tissue and an increasing ratio of high valence metal ions. To overcome these challenges, a novel nanotherapeutic approach, named GOx-CuCaP-DSF, has been proposed. This approach involves the design of nanotherapeutics that aim to self-supply H2O2 within cancer cells and provide a supplement of low valence metal ions to enhance the performance of CDT. GOx-CuCaP-DSF nanotherapeutics are engineered by incorporating glucose oxidase (GOx) into Ca2+-doped calcium phosphate (CaP) nanoparticles and loading disulfiram (DSF) through surface adsorption. Under the tumor microenvironment, GOx catalyzes the conversion of tumor-overexpressed glucose (Glu) to liberate H2O2. The degradation of CaP further lowers the pH, facilitating the release of Cu2+ ions and DSF. The rapid reaction between Cu2+ and DSF leads to the generation of Cu+, increasing the Cu+/Cu2+ ratio and promoting the Cu+-based Fenton reaction, which enhances the efficiency of CDT. Simultaneously, DSF undergoes conversion to diethyldithiocarbamate acid (ET), forming a copper(II) complex (Cu(II)ET) by strong chelation with Cu ions. This Cu(II)ET complex, a potent chemotherapeutic drug, exhibits a synergistic therapeutic effect in combination with CDT. Moreover, the elevated Cu+ species resulting from DSF reaction promotes the aggregation of toxic mitochondrial proteins, leading to cell cuproptosis. Overall, the strategy of integrating the chemodynamic therapy efficiency of the Fenton reaction with the activation of efficacious cuproptosis using a chemotherapeutic drug presents a promising avenue for enhancing the effectiveness of multi-modal anti-tumor treatments.

Corticotropin-releasing factor neurones in the paraventricular nucleus of the hypothalamus modulate isoflurane anaesthesia and its responses to acute stress in mice.

BACKGROUND: Corticotropin-releasing factor (CRF) neurones in the paraventricular nucleus (PVN) of the hypothalamus (PVNCRF neurones) can promote wakefulness and are activated under anaesthesia. However, whether these neurones contribute to anaesthetic effects is unknown. METHODS: With a combination of chemogenetic and molecular approaches, we examined the roles of PVNCRF neurones in isoflurane anaesthesia in mice and further explored the underlying cellular and molecular mechanisms. RESULTS: PVN neurones exhibited increased Fos expression during isoflurane anaesthesia (mean [standard deviation], 218 [69.3] vs 21.3 [7.3]; P<0.001), and ∼75% were PVNCRF neurones. Chemogenetic inhibition of PVNCRF neurones facilitated emergence from isoflurane anaesthesia (11.7 [1.1] vs 13.9 [1.2] min; P=0.001), whereas chemogenetic activation of these neurones delayed emergence from isoflurane anaesthesia (16.9 [1.2] vs 13.9 [1.3] min; P=0.002). Isoflurane exposure increased CRF protein expression in PVN (4.0 [0.1] vs 2.2 [0.3], respectively; P<0.001). Knockdown of CRF in PVNCRF neurones mimicked the effects of chemogenetic inhibition of PVNCRF neurones in facilitating emergence (9.6 [1.1] vs 13.0 [1.4] min; P=0.003) and also abolished the effects of chemogenetic activation of PVNCRF neurones on delaying emergence from isoflurane anaesthesia (10.3 [1.3] vs 16.0 [2.6] min; P<0.001). Acute, but not chronic, stress delayed emergence from isoflurane anaesthesia (15.5 [1.5] vs 13.0 [1.4] min; P=0.004). This effect was reversed by chemogenetic inhibition of PVNCRF neurones (11.7 [1.6] vs 14.7 [1.4] min; P=0.001) or knockdown of CRF in PVNCRF neurones (12.3 [1.5] vs 15.3 [1.6] min; P=0.002). CONCLUSIONS: CRF neurones in the PVN of the hypothalamus neurones modulate isoflurane anaesthesia and acute stress effects on anaesthesia through CRF signalling.

VTA-NAc glutaminergic projection involves in the regulation of pain and pain-related anxiety.

Background: Besides the established role of dopamine neurons and projections in nociceptive stimuli, the involvement of ventral tegmental area (VTA) glutamatergic projections to nucleus accumbens (NAc) in pain remains unknown. In the present study, we aimed to examine the role of VTA glutamatergic projections to NAc in painful stimuli and its related behavioral changes. Methods: Unilateral chronic constrictive injury (CCI) of sciatic nerve or intraplantar hind paw injections (i.pl.) of complete Freund's adjuvant (CFA) were used to develop pathological pain models in wild-type and VGluT2-Cre mice. The involvement of VTA glutamatergic neurons with projections to NAc in CCI-induced pain model was noted by c-Fos labeling and firing rate recordings. Pain response and pain-related behavior changes to the artificial manipulation of the VTA glutamatergic projections to NAc were observed by Hargreaves tests, von Frey tests, open field tests, elevated maze tests, and sucrose preference tests. Results: Glutamatergic neurons in VTA had efferent inputs to shell area of the NAc. The CCI pain model significantly increased neuronal activity and firing rate in VTA glutamate neurons with projections to NAc. The photoinhibition of these glutamatergic projections relieved CCI-induced neuropathic pain and CFA-induced acute and chronic inflammatory pain. Moreover, pathological neuropathic pain-induced anxiety and less sucrose preference were also relieved by inhibiting the VTA glutamatergic projections to NAc. Conclusion: Together, glutamatergic inputs from VTA to NAc contribute to chronic neuropathic and inflammatory pain and pain-related anxiety and depressive behaviors, providing a mechanism for developing novel therapeutic methods.

Novel Arginine End-Tagging Antimicrobial Peptides to Combat Multidrug-Resistant Bacteria.

The emergence of multidrug-resistant microorganisms has been termed one of the most common global health threats, emphasizing the discovery of new antibacterial agents. To address this issue, we engineered peptides harboring "RWWWR" as a central motif plus arginine (R) end-tagging and then tested them in vitro and in vivo. Our results demonstrate that Pep 6, one of the engineered peptides, shows great potential in combating Escherichia coli bacteremia and the Staphylococcus aureus skin burn infection model, which induces a 62-90% reduction in bacterial burden. Remarkably, after long serial passages of S. aureus and E. coli for 30 days, Pep 6 is still highly efficient in killing pathogens, compared with 64- and 128-fold increase in minimal inhibitory concentrations (MICs) for vancomycin and polymyxin B, respectively. We also found that Pep 6 exhibited robust biofilm-inhibiting activity and eliminated 61.33% of the mature methicillin-resistant Staphylococcus aureus (MRSA) biofilm with concentration in the MIC level. These results suggest that the RWWWR motif and binding of arginine end-tagging could be harnessed as a new agent for combating multidrug-resistant bacteria.

Wogonin alleviates liver injury in sepsis through Nrf2-mediated NF-κB signalling suppression.

Sepsis is a life-threatening organ dysfunction syndrome, and liver is a susceptible target organ in sepsis, because the activation of inflammatory pathways contributes to septic liver injury. Oxidative stress has been documented to participate in septic liver injury, because it not only directly induces oxidative genotoxicity, but also exacerbates inflammatory pathways to potentiate damage of liver. Therefore, to ameliorate oxidative stress is promising for protecting liver in sepsis. Wogonin is the compound extracted from the medicinal plant Scutellaria baicalensis Geogi and was found to exert therapeutic effects in multiple inflammatory diseases via alleviation of oxidative stress. However, whether wogonin is able to mitigate septic liver injury remains unknown. Herein, we firstly proved that wogonin treatment could improve survival of mice with lipopolysaccharide (LPS)- or caecal ligation and puncture (CLP)-induced sepsis, together with restoration of reduced body temperature and respiratory rate, and suppression of several pro-inflammatory cytokines in circulation. Then, we found that wogonin effectively alleviated liver injury via potentiation of the anti-oxidative capacity. To be specific, wogonin activated Nrf2 thereby promoting expressions of anti-oxidative enzymes including NQO-1, GST, HO-1, SOD1 and SOD2 in hepatocytes. Moreover, wogonin-induced Nrf2 activation could suppress NF-κB-regulated up-regulation of pro-inflammatory cytokines. Ultimately, we provided in vivo evidence that wogonin activated Nrf2 signalling, potentiated anti-oxidative enzymes and inhibited NF-κB-regulated pro-inflammatory signalling. Taken together, this study demonstrates that wogonin can be the potential therapeutic agent for alleviating liver injury in sepsis by simultaneously ameliorating oxidative stress and inflammatory response through the activation of Nrf2.

Rapid Screening and Identification of Antitumor Ingredients from the Mangrove Endophytic Fungus Using an Enzyme-Immobilized Magnetic Nanoparticulate System.

As a consequence of recent progression in biomedicine and nanotechnology, nanoparticle-based systems have evolved as a new method with extensive applications in responsive therapy, multimodal imaging, drug delivery and natural product separation. Meanwhile, the magnetic nanoparticulate system has aroused great interest for separation and purification because of its excellent magnetic properties. Phospholipase A2 (PLA2) is a highly expressed regulator to promote the growth of various cancers and is an ideal target to treat cancers. In this study, a novel strategy based on ligand-receptor interactions to discover novel PLA2 inhibitors was established, in which PLA2-functionalized Fe3O4@PLGA-PEG-NH2 magnetic nanoparticles were used as a supporting material combined with high-performance liquid chromatography-mass spectrometry, aiming to accelerate the discovery of novel PLA2 inhibitors from natural sources such as mangrove endophytic fungi. Under the optimized ligand fishing conditions, six target compounds were ultimately fished and identified to be cyclic peptides (1-3) and sterols (4-6), which compounds 1, 2 and 4-6 have well-documented cytotoxicities. Compound 3 exerted better inhibitory effect on A549 cells by experiment. In conclusion, PLA2-functionalized Fe3O4@PLGA-PEG-NH2 magnetic nanoparticles-based ligand fishing provided a feasible, selective and effective platform for the efficient screening and identification of antitumor components from natural products.

Mitochondria-targeting graphene oxide nanocomposites for fluorescence imaging-guided synergistic phototherapy of drug-resistant osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and young adults. Drug-resistant osteosarcoma often results in chemotherapy failure. Therefore, new treatments aimed at novel therapeutic targets are urgently needed for the treatment of drug-resistant osteosarcoma. Mitochondria-targeted phototherapy, i.e., synergistic photodynamic/photothermal therapy, has emerged as a highly promising strategy for treating drug-resistant tumors. This study proposed a new nano-drug delivery system based on near-infrared imaging and multifunctional graphene, which can target mitochondria and show synergistic phototherapy, with preferential accumulation in tumors. METHODS AND RESULTS: Based on our previous study, (4-carboxybutyl) triphenyl phosphonium bromide (TPP), a mitochondria-targeting ligand, was conjugated to indocyanine green (ICG)-loaded, polyethylenimine-modified PEGylated nanographene oxide sheets (TPP-PPG@ICG) to promote mitochondrial accumulation after cellular internalization. Thereafter, exposure to a single dose of near-infrared irradiation enabled synergistic photodynamic and photothermal therapy, which simultaneously inhibited adenosine triphosphate synthesis and mitochondrial function. Induction of intrinsic apoptosis assisted in surmounting drug resistance and caused tumor cell death. After fluorescence imaging-guided synergistic phototherapy, the mitochondria-targeting, multifunctional graphene-based, drug-delivery system showed highly selective anticancer efficiency in vitro and in vivo, resulting in marked inhibition of tumor progression without noticeable toxicity in mice bearing doxorubicin-resistant MG63 tumor cells. CONCLUSION: The mitochondria-targeting TPP-PPG@ICG nanocomposite constitutes a new class of nanomedicine for fluorescence imaging-guided synergistic phototherapy and shows promise for treating drug-resistant osteosarcoma.

Shenkang VII Recipe Attenuates Unilateral Ureteral Obstruction-induced Renal Fibrosis via TGF-ß/Smad, NF-κB and SHH Signaling Pathway.

This study aimed to explore the protective effects of the traditional Chinese Medicine formula Shenkang VII recipe (SK-7) on renal fibrosis and the mechanisms. Renal fibrosis was induced by unilateral ureteral obstruction (UUO) in rats. The rats were then divided into 5 groups: control group (Sham operation), UUO model group, UUO model plus low to high doses of SK-7 (0.5, 1.0, or 2.0 g/kg/day, for 14 days) groups. The animals were sacrificed on the 7th or 14th day. Kidney tissues were collected for histopathological examinations (hematoxylin and eosin and Masson's trichrome staining). Immunohistochemistry was used to detect the expression of collagen type III (Col III), fibronectin (FN), α-smooth muscle actin (α-SMA), TIMP metallopeptidase inhibitor 2 (TIMP2), matrix metallopeptidase 2 (MMP2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and monocyte chemotactic protein-1 (MCP-1). The TGF-ß1/Smad, NF-kB and Sonic hedgehog signaling proteins were detected by Western blotting. Our results showed that SK-7 prevented UUO-induced renal injury and accumulation of collagen fibrils. Renal fibrosis biomarkers Col III, FN, α-SMA and TIMP2 were increased in the rats after UUO and decreased by SK-7, while MMP2 was upregulated after treatment. SK-7 also suppressed the levels of TNF-α, IL-1ß and MCP-1 in UUO rats. In addition, SK-7 inhibited activation of the TGF-ß/Smad, NF-κB and sonic hedgehog signaling (SHH) pathways. Taken together, these findings suggest that SK-7 may regulate the synthesis and degradation of extracellular matrix, reduce inflammation and suppress the proliferation of fibroblasts, by blocking the TGF-ß1/Smad, NF-κB and SHH signaling pathways to exert its anti-renal fibrosis effect in UUO rats.

[Effect of moxibustion on cardiac function and expression of autophagy-related proteins of cardiomyocytes in chronic heart failure rats].

OBJECTIVE: To observe the effect of moxibustion on cardiac function and expression of myocardial tumor suppressor protein p53, mammalian target of rapamycin (mTOR) and phosphorylated(p)-mTOR (excessive autophagy-associated proteins of cardiomyocytes) in rats with chronic heart failure (CHF), so as to explore its mechanisms underlying improvement of CHF. METHODS: SD rats were divided into blank control (n＝11), model(n＝8), autophagy activator (n＝8), autophagy inhibitor (n＝9) and moxibustion(n＝9) groups. The CHF model was established by i．p. injection of Doxorubicin Hydrochloride (DOX, 1 mg/mL, 1-4 mg/kg) every other day. Moxibustion was applied to bilateral "Feishu" (BL13) and "Xinshu" (BL15) for 20 min, 5 times a week for 3 weeks. Rats of the autophagy activator group received gavage of Rapamycin (RAPA, 2 mg/kg) and those of the autophagy inhibitor group received i．p. injection of Methyladenine (3-MA, 15 mg/kg) 5 times a week for 3 weeks after successful modeling. The heart weight and body weight were measured to calculate heart mass index (HW/BW＝heart weight ÷ body weight). Cardiac output (CO) and heart rate (HR) were measured by using a cardiac function meter. Serum N-terminal pro-brain natriuretic peptide (NT-pro BNP) content was assayed by using ELISA, and the expression of myocardial p53, p-mTOR and mTOR proteins was examined by Western blot. RESULTS: (1) Compared with the blank control group, the HR, HW/BW, NT-pro BNP content and p53 expression levels were significantly increased (P<0.01), and the CO and ratio of p-mTOR/mTOR were significantly decreased in the model group (P<0.01). (2) Compared with the model group, the HR, HW/BW and NT-pro BNP content of the autophagy inhibitor and moxibustion groups were significantly decreased (P<0.01, P<0.05), and CO and p-mTOR/mTOR ratio were significantly increased in both autophagy inhibitor and moxibustion groups (P<0.01). (3) Compared with the autophagy activator group, the levels of HR, HW/BW, NT-pro BNP and p53 in the autophagy inhibitor and moxibustion groups were significantly lower (P<0.01), and those of CO and p-mTOR/mTOR levels were significantly higher (P<0.01). CONCLUSION: Moxibustion, similar to the autophagy inhibitor, has a protective action on myocardium in CHF rats, which is possible by preventing over expression of myocardial autophagy-associated proteins during CHF.

Adsorption and desorption characteristics of ginsenosides from Panax ginseng C. A. Meyer on middle-pressure chromatogram isolated gels.

Four types of middle-pressure chromatogram isolated gels are evaluated for adsorption or desorption characteristics of ginsenosides from Panax ginseng. Among them, SP207SS and SP2MGS were selected for dynamic investigations based on their static adsorption or desorption capacity of total ginsenoside. Their adsorption kinetics was better explained by pseudosecond-order model and isotherms were preferably fitted to Langmuir model. Dynamic breakthrough experiments indicated an optimum sample loading speed of 4 bed volume/h for either SP207SS or SP2MGS. Desorption speed was determined to be 2 bed volume/h according to desorption amount of total ginsenoside in their effluents. Eight ginsenosides were identified and quantified by high performance liquid chromatography-triple quadropole-mass spectrometry in total ginsenoside extract and different fractions during stepwise dynamic elution. For SP207SS, 27.62% of loaded ginsenosides was detected in 40% ethanol fraction, while 59.12% of them were found in 60% ethanol fraction. As on SP2MGS, the number went to 53.71 and 44.43%, respectively. Recovery rate of ginsenosides were calculated to 78.65% for SP207SS and 89.53% for SP2MGS, respectively. Intriguingly, content of Rg1 and Re in 40% ethanol fraction from SP207SS became 20.1 and 18.6 times higher than that in total ginsenoside extract by one-step elution, which could be leveraged for the facile enrichment of these two ginsenosides from natural sources.

Statistical Optimization of Polysaccharides Production by the Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) in Solid-State Fermentation Using Highland Barley Grains.

Ganoderma lucidum is a widely used medicinal mushroom in traditional Chinese medicine that creates a diverse set of bioactive compounds. Highland barley, a typical nutrition-balanced crop, is not convenient for direct consumption but its nutritional characteristics meet the modern requirements of health food. In the present study, barley grains were used as substrates on solid-state fermentation (SSF) of G. lucidum. Statistical optimization of media composition was employed for enhancing the production of polysaccharides. Peptone, medlar, and KH2PO4 were identified as the most important components for producing polysaccharide. Based on the one-factor-at-a-time experimentation, a quadratic regression model with the polysaccharide contents as the response value was established by central composite design (CCD). The results showed that the predicted variables were 2.38% peptone, 1.14% medlar, and 0.25% KH2PO4 for the maximum yield of predicted polysaccharides of 11.64% in the fermented substrate. The experimental polysaccharides obtained using the predicted optimum media composition constituted 11.61% of the fermented substrate, which validates the high degree of accuracy of optimization for enhanced production of polysaccharides by SSF. This study suggested that in the process of barley grains fermentation by G. lucidum for polysaccharides production, the optimized SSF substrate consists of 71.4% barley grains, 2.38% peptone, 1.14% medlar, 0.25% KH2PO4, 2.5% glucose, 0.25% MgSO4 · 7H2O, and 1% CaCO3. According to this study, the strain G. lucidum 00679 showed a good fermentation property by optimizing the media. It might be a candidate industrial strain for further process optimization and scale-up study.

The PI3K/Akt and NF-κB signaling pathways are involved in the protective effects of Lithocarpus polystachyus (sweet tea) on APAP-induced oxidative stress injury in mice.

Acetaminophen (APAP)-induced acute liver injury (ALI) is a health issue that has gradually attracted attention, and is often regarded as a model of drug-induced hepatotoxicity. The leaves of Lithocarpus polystachyus Rehd. (named as "sweet tea", ST) usually serve as tea drink and folk medicine for healthcare in the southwest part of China. In previous reports, it has been proven to protect various animal models, except for APAP-induced liver injury model. Therefore, this study initially explored the protective effect of ST leaf extract (STL-E) on hepatotoxicity induced by APAP in ICR mice. STL-E of 50 and 100 mg kg-1 were given to each group for 7 days. ALI was intraperitoneally induced by APAP treatment (i.p. 250 mg per kg body weight). Biochemical markers, levels of inflammatory factors, histopathological staining and western blotting were used to analyze the inflammation and apoptosis of liver tissues. Interestingly, the treatment with STL-E significantly attenuated APAP-induced liver injury (p < 0.05). Moreover, STL-E partially mitigated APAP-induced liver injury by effectively activating the PI3K/Akt pathway and inhibiting the NF-κB pathway. In a word, STL-E protected liver against APAP-induced hepatotoxicity by inhibiting the PI3K/Akt-mediated apoptosis signal pathway and inhibiting the NF-κB-mediated signaling pathway.

Gastric phytobezoars: the therapeutic experience of 63 patients in Northern China.

INTRODUCTION: Sixty-three patients with gastric phytobezoars were reviewed. METHODS: forty-eight (76.2%) patients received endoscopic combined with chemical therapies and 15 (23.8%) received only chemical therapy initially. Fifty-one (81.0%) patients achieved complete removal (only chemical therapy 14/15), while 12 (19.0%) received further endoscopic therapies. RESULTS: finally, 62 (98.4%) patients achieved a complete removal. Considering only patients with combined treatment as a first approach, treatment success was associated with a softer phytobezoar consistency (p = 0.023). CONCLUSION: in conclusion, most patients achieve a favorable outcome. Chemical therapy is useful in selected cases. Repeated endoscopic therapies may be needed in order to completely remove phytobezoars with a hard consistency.

Active Components and Mechanism of Rhei Radix et Rhizoma on Renal Fibrosis Based on Network Pharmacology / 中国实验方剂学杂志

Objective::To explore the active components, potential targets and signaling pathways of Rhei Radix et Rhizoma in the treatment of renal fibrosis based on the network pharmacology method, and then to verify the target genes in vitro. Method::Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID) were retrieved to obtain the main active ingredients of Rhei Radix et Rhizoma. The potential anti-renal fibrosis targets of Rhei Radix et Rhizoma were predicted by similarity ensemble approach (SEA), Swiss Institute of Bioinformatics (SIB) and GeneCards Database. Target protein-protein interaction (PPI) network was constructed by using String Version 10.5 database. David 6.8 software was used for gene ontology (GO) enrichment analysis and the Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of the key targets. Cytoscape Version 3.6.0 software was used for visualized analysis of PPI network, active ingredient-key target network and the ingredient-target-signal pathway network. In combination with Malachards database, the signal pathways with high correlation with renal fibrosis were screened. Then, cell experiments were used for verification: HK-2 cells were selected to establish fibrosis model by transforming growth factor-β1 (TGF-β1) stimulation. The cells were treated with rhein for 48 hours. Western blot assay was used to detect the protein expression level of hypoxia inducible factor-1 α (HIF-1 α), vascular endothelial growth factor (VEGF), and platelet-derived growth factor receptor-α (PDGFR-α). Protein expression levels of E-cadherin and α smooth muscle actin (α-SMA) were detected by immunofluorescence. Apoptosis was detected with flow cytometry. Result::Totally 17 active ingredients of Rhei Radix et Rhizoma and 424 targets of anti-renal fibrosis effect were screened out, including five key targets: protein kinase B(Akt)1, mitogen activated protein kinases 3(MAPK3), epidermal growth factor receptor(EGFR), interleukin(IL)-6 and VEGFA in turn. The biological process of GO enrichment mainly involved signal transduction, cell proliferation and apoptotic process. The results of KEGG pathway enrichment showed that phosphatidylinositol 3-kinase(PI3K)/Akt, HIF-1, VEGF, and forkhead transcription factor (FoxO) pathways were related to the anti-renal fibrosis mechanism of Rhei Radix et Rhizoma. Results of the in vitro experiment proved that rhein could inhibit the expression of E-cadherin, α-SMA, HIF-1α, VEGF and PDGFR-α. In addition, rhein inhibited apoptosis induced by TGF-β1 in HK-2 cells. Part of the prediction results of network pharmacology were verified. Conclusion::This study reflects the multi-component, multi-target and multi-pathway mechanism characteristics of Rhei Radix et Rhizoma. The mechanisms of its anti-renal fibrosis effects may be related to inhibiting HIF-1 α / VEGF /PDGFR-α signaling pathway, apoptosis and epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells.

[Catheter balloon dilation combined with acupuncture for cricopharyngeal achalasia after brain stem infarction: a randomized controlled trial].

OBJECTIVE: To screen the optimal acupuncture regimen for cricopharyngeal achalasia (CPA) after brain stem infarction and compare the therapeutic effect between the combined therapy of catheter balloon dilation and acupuncture and the simple application of catheter balloon dilation. METHODS: The patients suffering from neuropathic dysphagia in CPA after brain stem infarction were selected as the subjects. After confirmed in the diagnosis with video fluoroscopic swallowing study (VFSS), they were randomized into 6 groups, 15 cases in each one, named group A (routine treatment), group B (catheter balloon dilation), group C1 (treated with acupuncture in local area), group C2 (treated with acupuncture based on zangfu differentiation), group C3 (treated with acupuncture at the local area and the acupoints based on zangfu differentiation) and group D (catheter balloon dilation combined with the optimal acupuncture). Two phases were included in the study. In the first phase of study, the therapeutic effect was compared among the three acupuncture groups, named C1, C2 and C3 group, so as to screen the optimal acupuncture regimen. In the group C1, the main acupoints included Fengchi (GB 20), Wangu (GB 12), Yifeng (TE 17) and three-tongue points (Extra). In the group C2, the main acupoints were Neiguan (PC 6), Tongli (HT 5), Zusanli (ST 36) and Sanyinjiao (SP 6) as well as the supplementary acupoints in accordance with the syndrome differentiation. In the group C1 and group C2, after deqi, the electroacupuncture was used, with continuous dense wave, 5 to 8 Hz in frequency. The needles were retained for 30 min. Acupuncture was given once a day, 5 treatments a week. Before treatment, in 6 weeks of treatment or after removal of gastric tube, the rehabilitation was evaluated. In the group C3, the acupoints, manipulation and treating course were same as the group C1 and group C2. In the 2nd phase of study, theresults of rehabilitation treatment were compared among the group A, group B and group D. The treatment was given once a day, 5 times a week. Before treatment, after gastric tube removal or in 6 weeks of treatment, the evaluation was conducted. The feeding-swallowing function grade and VFSS were adopted in the evaluation among the above 6 groups. RESULTS: ① In the VFSS comparison at 1st phase of study after treatment, the food transporting ability at oral dysphagia, the results in the group C3 and group C1 were better obviously than the group C2 (both P<0.05). For the improvement in aspiration, the result in the group C3 was better obviously than the group C2 (P<0.05). In comparison of the three acupuncture groups with the group A, the difference was not significant statisticallys in the extubation rate among the four groups (P>0.05). The severity of dysphagia in the group C3 was milder than the group C2 and group A (both P<0.05). ② In the VFSS comparison at the 2nd phase of study, for the food transporting ability, the results in the group D and the group B were obviously better than the group A (both P<0.05). Regarding the function at the pharyngeal dysphagia and aspiration, the results in the group D were better than the group B and group A, those in the group B were better than the group A (all P<0.05). The difference in the extubation rate among the group A, group B and group D after treatment was significant statistically (P<0.01), of which, the extubation rate in the group D was the highest and the rate in the group A was the lowest. The dysphagia degree in the group D was milder than the group B and group A and that in the group B was milder than the group A (all P<0.05). CONCLUSION: In the study of the different acupuncture methods, the acupuncture at the local acupoints and the acupoints selected based on zangfu differentiation is the optimal acupuncture regimen for cricopharyngeal achalasia after brain stem infarction. The catheter balloon dilation combined with acupuncture present the synergistc effect on cricopharyngeal achalasia after brain stem infarction, obviously relieve dysphagia and reduce aspiration.

Huang Qi Tong Bi Decoction Attenuates Myocardial Ischemia-Reperfusion Injury via HMGB1/TLR/NF-κB Pathway.

The aim of this study was to study the protective effect of Huang Qi Tong Bi Decoction (HQTBT) on the heart of rats. Ischemia-reperfusion injury was established by coronary artery ligation. Proinflammatory cytokines were decreased by XFZY in coronary artery ligated rats. ST segment was also restored with the treatment of HQTBT. Triphenyltetrazole chloride (TTC) staining and pathological analysis showed that HQTBT reduced myocardial injury. Besides, the expressions of HMGB1/TLR/NF-κB pathway in rats were significantly decreased by HQTBT. This study shows that HQTBT inhibited inflammatory reaction on myocardial injury in rats.

[Analysis of the academic features of the moxibustion of Xin'an physicians].

Xin'an acupuncture and moxibustion physicians have a lot of talented people. Their academic theories promote the development of moxibustion theory. WANG Guo-rui used acupuncture and moxibustion together in clinic, and emphasized reinforcing and reducing method. Moxibustion was performed with unique matching acupoint according to different cases. WANG Ji proposed the theory "moxibustion can cure sores, and has reinforcing and reducing method""scars block the movement of qi and do not use moxibustion when there is no disease". XU Chun-fu elaborated on the theory of moxibustion, which involved a wide range of ideas and advocated the idea of combining acupuncture with drugs. WU Qian put forward the theory "moxibustion is mostly used at acupoints on the back, and can cure multiple syndromes" "focus on the use of miraculous acupoints for the treatment of emergency diseases" "moxibustion must be treated with enough moxibustion to cure the disease". WU Yi-ding thonght that only by carefully identifying the types of diseases and using corresponding acupoints could have a very good curative effect; moxibustion had indications and contraindications, so be careful when used it; moxibustion was divided into yin and yang, also divided into reinforcing and reducing methods; sores were suitable for moxibustion and heat syndrome could also be used by moxibustion. He also believed that moxibustion was as important as acupuncture with the complementary relationship. Hence, the valuable significance of moxibustion in clinical practice is explored through the collection of the academic thoughts of WANG Guo-rui, WANG Ji, XU Chun-fu, WU Qian and WU Yi-ding.

Analysis of the academic features of the moxibustion of ' physicians / 中国针灸

' acupuncture and moxibustion physicians have a lot of talented people. Their academic theories promote the development of moxibustion theory. - used acupuncture and moxibustion together in clinic, and emphasized reinforcing and reducing method. Moxibustion was performed with unique matching acupoint according to different cases. proposed the theory "moxibustion can cure sores, and has reinforcing and reducing method"scars block the movement of and do not use moxibustion when there is no disease". - elaborated on the theory of moxibustion, which involved a wide range of ideas and advocated the idea of combining acupuncture with drugs. put forward the theory "moxibustion is mostly used at acupoints on the back, and can cure multiple syndromes" "focus on the use of miraculous acupoints for the treatment of emergency diseases" "moxibustion must be treated with enough moxibustion to cure the disease". - thonght that only by carefully identifying the types of diseases and using corresponding acupoints could have a very good curative effect; moxibustion had indications and contraindications, so be careful when used it; moxibustion was divided into and , also divided into reinforcing and reducing methods; sores were suitable for moxibustion and heat syndrome could also be used by moxibustion. He also believed that moxibustion was as important as acupuncture with the complementary relationship. Hence, the valuable significance of moxibustion in clinical practice is explored through the collection of the academic thoughts of -, , -, and -.

Catheter balloon dilation combined with acupuncture for cricopharyngeal achalasia after brain stem infarction: a randomized controlled trial / 中国针灸

OBJECTIVE@#To screen the optimal acupuncture regimen for cricopharyngeal achalasia (CPA) after brain stem infarction and compare the therapeutic effect between the combined therapy of catheter balloon dilation and acupuncture and the simple application of catheter balloon dilation.@*METHODS@#The patients suffering from neuropathic dysphagia in CPA after brain stem infarction were selected as the subjects. After confirmed in the diagnosis with video fluoroscopic swallowing study (VFSS), they were randomized into 6 groups, 15 cases in each one, named group A (routine treatment), group B (catheter balloon dilation), group C1 (treated with acupuncture in local area), group C2 (treated with acupuncture based on differentiation), group C3 (treated with acupuncture at the local area and the acupoints based on differentiation) and group D (catheter balloon dilation combined with the optimal acupuncture). Two phases were included in the study. In the first phase of study, the therapeutic effect was compared among the three acupuncture groups, named C1, C2 and C3 group, so as to screen the optimal acupuncture regimen. In the group C1, the main acupoints included Fengchi (GB 20), Wangu (GB 12), Yifeng (TE 17) and three-tongue points (Extra). In the group C2, the main acupoints were Neiguan (PC 6), Tongli (HT 5), Zusanli (ST 36) and Sanyinjiao (SP 6) as well as the supplementary acupoints in accordance with the syndrome differentiation. In the group C1 and group C2, after , the electroacupuncture was used, with continuous dense wave, 5 to 8 Hz in frequency. The needles were retained for 30 min. Acupuncture was given once a day, 5 treatments a week. Before treatment, in 6 weeks of treatment or after removal of gastric tube, the rehabilitation was evaluated. In the group C3, the acupoints, manipulation and treating course were same as the group C1 and group C2. In the 2nd phase of study, theresults of rehabilitation treatment were compared among the group A, group B and group D. The treatment was given once a day, 5 times a week. Before treatment, after gastric tube removal or in 6 weeks of treatment, the evaluation was conducted. The feedingswallowing function grade and VFSS were adopted in the evaluation among the above 6 groups.@*RESULTS@#① In the VFSS comparison at 1st phase of study after treatment, the food transporting ability at oral dysphagia, the results in the group C3 and group C1 were better obviously than the group C2 (both 0.05). The severity of dysphagia in the group C3 was milder than the group C2 and group A (both <0.05). ② In the VFSS comparison at the 2nd phase of study, for the food transporting ability, the results in the group D and the group B were obviously better than the group A (both <0.05). Regarding the function at the pharyngeal dysphagia and aspiration, the results in the group D were better than the group B and group A, those in the group B were better than the group A (all <0.05). The difference in the extubation rate among the group A, group B and group D after treatment was significant statistically (<0.01), of which, the extubation rate in the group D was the highest and the rate in the group A was the lowest. The dysphagia degree in the group D was milder than the group B and group A and that in the group B was milder than the group A (all <0.05).@*CONCLUSION@#In the study of the different acupuncture methods, the acupuncture at the local acupoints and the acupoints selected based on differentiation is the optimal acupuncture regimen for cricopharyngeal achalasia after brain stem infarction. The catheter balloon dilation combined with acupuncture present the synergistc effect on cricopharyngeal achalasia after brain stem infarction, obviously relieve dysphagia and reduce aspiration.