Miao medicine Gu Yan Xiao tincture inhibits mTOR to stimulate chondrocyte autophagy in a rabbit model of osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: The Gu Yan Xiao tincture, a blend of traditional Chinese herbs, is traditionally used for osteoarthritis and related pain. This study investigated its mechanism of action in order to rationalize and validate its therapeutic use. AIM OF THE STUDY: This study analyzed, in a rabbit model of knee osteoarthritis, whether and how Gu Yan Xiao tincture exerts therapeutic benefits by modulating chondrocyte autophagy. MATERIALS AND METHODS: The active constituents within the GYX tincture were identified using liquid chromatography-mass spectrometry. The rabbit model was established by injecting animals with type II collagenase intra-articularly, and the effects of topically applied tincture were examined on osteoarthritis lesions of the knee using histopathology, micro-computed tomography and x-ray imaging. Effects of the tincture were also evaluated on levels of inflammatory cytokines, matrix metalloproteases, and autophagy in chondrocytes. As a positive control, animals were treated with sodium diclofenac. RESULTS: The tincture mitigated the reduction in joint space, hyperplasia of the synovium and matrix metalloproteases in serum that occurred after injection of type II collagenase in rabbits. These therapeutic effects were associated with inhibition of mTOR and activation of autophagy in articular chondrocytes. Inhibiting mTOR with rapamycin potentiated the therapeutic effects of the tincture, while inhibiting autophagy with 3-methyladenine antagonized them. CONCLUSIONS: Gu Yan Xiao tincture mitigates tissue injury in a rabbit model of osteoarthritis, at least in part by inhibiting mTOR and thereby promoting autophagy in chondrocytes. These results rationalize the use of the tincture not only against osteoarthritis but also potentially other diseases involving inhibition of autophagy in bones and joints.

Characterization of the metabolism of aloin A/B and aloesin in rats using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Aloin A/B and aloesin are the major bioactive constituents in Aloe vera, with diverse pharmacological activities, including anti-bacterial, anti-tumour, anti-inflammatory and intestinal regulation. However, the in vivo metabolism of aloin A/B and aloesin is still unclear. In this study, the metabolic processes of aloin A/B and aloesin in rats were investigated using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and MetaboLynx™ software with the mass defect filter technique. Based on the proposed method, the prototype components of three compounds were all detected in rat plasma, urine and feces. Meanwhile, 25 aloin A/B metabolites (six phase I, three phase II, 16 phase I combined with phase II) and three aloesin metabolites (two phase I and one phase II) were detected in rats after oral administration of aloin A, aloin B and aloesin, and the main biotransformation reactions were hydroxylation, oxidation, methylation, acetylation and glucuronidation. In addition, aloin A and aloin B can be transformed into each other in vivo and the metabolic profiles of aloin A and aloin B are identical. These results provide essential data for further pharmaceutical research and clinical application of aloin A/B and aloesin.

[Effect of Buyi Pishen acupuncture on inflammatory factor and cartilage matrix in adjuvant arthritis rats].

OBJECTIVE: To observe the effect of Buyi Pishen acupuncture (acupuncture for invigorating spleen and kidney) on inflammatory factor and synovial cartilage matrix in adjuvant arthritis (AA) rats, and to explore the mechanism of acupuncture for rheumatoid arthritis (RA). METHODS: A total of 60 clean male Wistar rats were randomized into a normal group, a model group, a tripterygium wilfordii polyglycoside tablet (TWP) group and an acupuncture group, 15 rats in each group. Rats in the model group, the TWP group and the acupuncture group received intradermal injection of Freund's complete adjuvant (FCA) at right hind foot pad to induce the AA model. TWP suspension of 8 mg/kg was given by gavage in the TWP group. Acupuncture was applied at "Shenshu" (BL 23), "Pishu" (BL 20) and right "Housanli" (ST 36), "Sanyinjiao" (SP 6), "Yanglingquan" (GB 34) in the acupuncture group, 15 min a time, once a day. The intervention was given 15 days in both TWP group and acupuncture group. The foot-pad swelling degree before modeling, before and after intervention and the arthritis index (AI) score before and after intervention were calculated; the serum levels of interleukin (IL)-1ß, IL-4, IL-10 and tumor necrosis factor-α (TNF-α) were detected by ELISA method; the ultrastructure and histomorphological changes of synovium issue were observed by transmission electron microscope and HE staining; the positive expression of matrix metalloproteinase (MMP)-3 and MMP-9 in synovium issue was detected by immunohistochemistry method. RESULTS: Before intervention, foot-pad swelling degree of the model group, the TWP group and the acupuncture group was increased compared with the normal group (P<0.01). After intervention, foot-pad swelling degree and AI score were increased compared with the normal group (P<0.01), foot-pad swelling degree and AI scores in the TWP group and the acupuncture group were lower than the model group (P<0.05), and those in the acupuncture group were decreased compared with the TWP group (P<0.05). The model group exhibited unclear nuclear membrane of synovial cells, chromatin pyknosis, massive inflammatory cell infiltration and hyperplasia in synovial tissue; the TWP group and the acupuncture group exhibited clear and smooth nuclear membrane of synovial cells, inapparent chromatin pyknosis, less inflammatory cell infiltration and hyperplasia in synovial tissue, the acupuncture group exhibited less matrix destruction as well. Compared with the normal group, serum levels of IL-1ß and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were increased (P<0.01), while serum levels of IL-4 and IL-10 were decreased (P<0.01) in the model group. Compared with the model group, serum levels of IL-1ß and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05, P<0.01), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the TWP group and the acupuncture group; compared with the TWP group, serum level of TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the acupuncture group. CONCLUSION: Buyi Pishen acupuncture can effectively improve the injury of articular cartilage in AA rats, its mechanism maybe related to reducing the inflammatory reaction in synovium and inhibiting the degradation of articular cartilage matrix.

[Evaluation of methodological and reporting quality of domestic clinical guidelines for hyperuricemia].

This study aims to evaluate the methodological and reporting quality of diagnosis and treatment guidelines for hyperuricemia as well as the expert consensuses and promote the understanding and application of the diagnosis and treatment guidelines for hyperuricemia. With "hyperuricemia" "guidelines" "consensus" "recommendations" as the key words in titles, the authors searched for the published clinical guidelines on hyperuricemia in Chinese against CNKI, Wanfang, VIP, Medlive and the official website of the industry association. The retrieval time limit was until May 31, 2021. The appraisal of guidelines for research and evaluation Ⅱ(AGREEⅡ) and the reporting items for practice guidelines in health care(RIGHT) were employed to evaluate the methodological quality and reporting quality of 14 guidelines/consensuses included. The average scores of the guidelines/consensuses were 80.85%(48.61%-98.61%) for the domain of scope and purpose, 34.52%(0-69.44%) for the domain of stakeholder involvement, 35.53%(6.25%-92.19%) for the domain of rigor of development, 55.85%(23.61%-86.11%) for the domain of clarity of presentation, 26.19%(0-76.04%) for the domain of applicability, and 21.42%(0-50.00%) for the domain of editorial independence. Nine guidelines/consensuses were of medium overall quality with grade B recommendation, and five guidelines/consensuses were of poor quality with grade C recommendation. The RIGHT classified the fourteen guidelines/consensuses into one of high reporting quality, three of medium reporting quality, and ten of low reporting quality. The results of this study indicate that the standardization and rigor of the methodological quality and the reporting quality of the clinical guidelines/consensuses for hyperuricemia in China remain to be strengthened.

Evaluating the efficacy and moderators of algorithm-guided antidepressant treatments of major depressive disorder.

BACKGROUND: In spite of numerous options, the most efficacious treatment for major depressive disorder (MDD) remains elusive. Algorithm-guided treatments (AGTs) are proposed to address inadequate remission and optimize treatment delivery. This study aimed to evaluate the clinical benefit of AGTs for MDD, and to explore specific moderators of treatment outcomes for individual patients. METHODS: The study recruited 987 patients with MDD across eight hospitals who were randomly assigned to AGT with escitalopram (AGT-E), AGT with mirtazapine (AGT-M), or treatment-as-usual (TAU). The outcomes were symptom remission, response rate, early improvement rate, subsymptom clusters improvement over time, the mean time to first remission, relapse rate at 6-months posttreatment follow-up, quality of life (QOL), and adverse events. RESUTLS: No significant differences were observed across groups in outcome, except that TAU showed significantly poorer QOL, higher relapse rates at 6-months posttreatment follow-up, and marginally significantly worse maximal burden of adverse events than the AGT groups. After 6 weeks of treatment initiation, remission rate did not significantly increase with extended treatment. AGT-M outperformed the TAU and AGT-E in treating sleep symptoms. AGT-E was less effective than AGT-M and TAU in patients with severe depression and somatic symptoms (DSSS). The superiority of TAU over AGTs was observed in recurrent MDD patients. CONCLUSION: Although the superiority of AGTs over TAU was limited by failure of alternative subsequent treatment, AGTs outperformed in QOL and relapse rate. Types of disease episode and DSSS were regarded as specific moderators in treatment of depression. These findings might contribute to future research on targeted antidepressant treatment.

Effect of Buyi Pishen acupuncture on inflammatory factor and cartilage matrix in adjuvant arthritis rats / 中国针灸

OBJECTIVE@#To observe the effect of Buyi Pishen acupuncture (acupuncture for invigorating spleen and kidney) on inflammatory factor and synovial cartilage matrix in adjuvant arthritis (AA) rats, and to explore the mechanism of acupuncture for rheumatoid arthritis (RA).@*METHODS@#A total of 60 clean male Wistar rats were randomized into a normal group, a model group, a tripterygium wilfordii polyglycoside tablet (TWP) group and an acupuncture group, 15 rats in each group. Rats in the model group, the TWP group and the acupuncture group received intradermal injection of Freund's complete adjuvant (FCA) at right hind foot pad to induce the AA model. TWP suspension of 8 mg/kg was given by gavage in the TWP group. Acupuncture was applied at "Shenshu" (BL 23), "Pishu" (BL 20) and right "Housanli" (ST 36), "Sanyinjiao" (SP 6), "Yanglingquan" (GB 34) in the acupuncture group, 15 min a time, once a day. The intervention was given 15 days in both TWP group and acupuncture group. The foot-pad swelling degree before modeling, before and after intervention and the arthritis index (AI) score before and after intervention were calculated; the serum levels of interleukin (IL)-1β, IL-4, IL-10 and tumor necrosis factor-α (TNF-α) were detected by ELISA method; the ultrastructure and histomorphological changes of synovium issue were observed by transmission electron microscope and HE staining; the positive expression of matrix metalloproteinase (MMP)-3 and MMP-9 in synovium issue was detected by immunohistochemistry method.@*RESULTS@#Before intervention, foot-pad swelling degree of the model group, the TWP group and the acupuncture group was increased compared with the normal group (P<0.01). After intervention, foot-pad swelling degree and AI score were increased compared with the normal group (P<0.01), foot-pad swelling degree and AI scores in the TWP group and the acupuncture group were lower than the model group (P<0.05), and those in the acupuncture group were decreased compared with the TWP group (P<0.05). The model group exhibited unclear nuclear membrane of synovial cells, chromatin pyknosis, massive inflammatory cell infiltration and hyperplasia in synovial tissue; the TWP group and the acupuncture group exhibited clear and smooth nuclear membrane of synovial cells, inapparent chromatin pyknosis, less inflammatory cell infiltration and hyperplasia in synovial tissue, the acupuncture group exhibited less matrix destruction as well. Compared with the normal group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were increased (P<0.01), while serum levels of IL-4 and IL-10 were decreased (P<0.01) in the model group. Compared with the model group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05, P<0.01), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the TWP group and the acupuncture group; compared with the TWP group, serum level of TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the acupuncture group.@*CONCLUSION@#Buyi Pishen acupuncture can effectively improve the injury of articular cartilage in AA rats, its mechanism maybe related to reducing the inflammatory reaction in synovium and inhibiting the degradation of articular cartilage matrix.

[Acupuncture regulates PI3K/Akt/mTOR signaling and up-regulates cell autophagy to protect sy-novial tissue of adjuvant arthritis rats].

OBJECTIVE: To observe the effect of acupuncture of "Yinlingquan"(SP9) and "Sanyinjiao"(SP6) on expression of phosphatidylinositol-3 kinase/protein kinase B/mammalian target protein of rapamycin (PI3K/Akt/mTOR) signaling in adjuvant arthritis (AA) rats, so as to explore its mechanism underlying improvement of AA. METHODS: Forty-eight male Wistar rats were randomly divided into normal control, AA model, acupuncture and medication (tripterygium wilfordii) groups, with 12 rats in each group. The AA model was established by putting the rats in a windy, cold and wet environment for 12 h, once every day for 21 days and injection of Freund's complete adjuvant (CFA) into the sole of the right hindlimb on the 21st day. Manual acupuncture stimulation was applied at SP9 and SP6 for 30 min/time, once a day for 21 days. Rats of the medication group received gavage of tripterygium wilfordii tablets solution (8 mg/kg), once a day for 21 days, and those of the normal control group and model group received gavage of the same amount of normal saline, once a day for 21 days. The degree of joint swelling and arthritis index (AI) were detected 1 day before modeling, 3 days after modeling, and 21 days after the treatment. Twenty-four hours after the last treatment, the contents of serum cytokines interleukin (IL)-17, IL-6 and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA); and changes of synovial ultrastructure were observed under electron microscope. Western blot was used to detect the expression levels of PI3K, Akt, phosphorylated protein kinase B (p-Akt), phosphorylated mammalian rapamycin target protein (p-mTOR), mTOR, microtubule associated protein 1 light chain 3B (LC3-Ⅱ) and mammalian atg6 homologous protein (Beclin-1) in the synovial membrane tissue. RESULTS: Compared with the normal control group, the joint swel-ling degree and AI, contents of serum TNF-α, IL-6 and IL-17, and the expression levels of PI3K, Akt, p-Akt, mTOR and p-mTOR in the synovium were increased in the model group (P<0.05), while the expression levels of LC3-Ⅱ and Beclin-1 proteins in the synovium were significantly decreased (P<0.05). Compared with the model group, the joint swelling degree and AI, contents of serum TNF-α, IL-6 and IL-17, and the expression levels of PI3K, Akt, p-Akt, mTOR and p-mTOR were significantly decreased in the acupuncture and medication groups (P<0.05), while the expresion levels of LC3-Ⅱ and Beclin-1 proteins were significantly increased （P<0.05）. Comparison between the two treatment groups showed that the therapeutic effects of acupuncture were obviously weaker than those of medication in down-regulating TNF-α and IL-6, Akt, p-Akt and mTOR levels (P<0.05) and in up-regulating Beclin-1 expression (P<0.05). Outcomes of electron microscope displayed widened nuclear membrane space, some fractured mitochondrial cristae with vacuoles, expanded rough endoplasmic reticulum, reduction of autophagosomes in the cytoplasm and ruptured synovial cell membrane in the model group, and increase of autophagosomes, deformed organelles in the acupuncture and medication groups. CONCLUSION: Acupuncture can relieve the inflammatory reactions and joint synovial injury of the affected joint in AA rats which may be associated with its effects in inhibiting PI3K/Akt/mTOR signaling and increasing the auto-phagy level of synovial cells.

[Effect of nuciferine on gut microbiota and inflammatory response in obese model mice].

The aim of this study was to elucidate the mechanism of nuciferine on alleviating obesity based on modulating gut microbiota, ameliorating chronic inflammation, and improving gut permeability. In this study, the obese model mice were induced by high-fat diet and then randomly divided into model group, and nuciferine group; some other mice of the same week age were fed with normal diet as normal group. In the modeling process, the mice were administered intragastrically(ig) for 12 weeks. In the course of both modeling and treatment, the body weight and food intake of mice in each group were measured weekly. After modeling and treatment, the Lee's index, weight percentage of inguinal subcutaneous fat, and the level of blood lipid in each group were measured. The pathological changes of adipocytes were observed by HE staining to evaluate the efficacy of nuciferine treatment in obese model mice. 16 S rRNA sequencing analysis was conducted to study the changes in diversity and abundance of gut microbiota after nuciferine treatment. Enzyme-linked immunosorbent assay(ELISA) and quantitative Real-time polymerase chain reaction(qPCR) were used to detect the levels of inflammatory factors interleukin-6(IL-6), interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α) and the expression of related genes in adipose tissue of mice in each group, so as to evaluate the effect of nuciferine on chronic inflammation of mice in obese model group. qPCR was used to detect the expression of occludin and tight junction protein 1(ZO-1)gene in colon tissure, so as to evaluate the effect of nuciferine on intestinal permeability of mice in obese group. Nuciferine decreased the body weight of obese mice, Lee's index, weight percentage of inguinal subcutaneous fat(P<0.05), and reduced the volume of adipocytes, decreased the level of total cholesterol(TC), triglyceride(TG), and low density lipoprotein cholesterol(LDL-C)(P<0.05) in serum, improved dysbacteriosis, increased the relative abundance of Alloprevotella, Turicibacter, and Lactobacillus, lowered the relative abundance of Helicobac-ter, decreased the expression of inflammatory cytokines IL-6, IL-1ß, and TNF-α genes in adipose tissue(P<0.01), decreased the levels of inflammatory cytokines IL-6, IL-1ß, and TNF-α in serum(P<0.05), and increased the expression of occludin and ZO-1 genes related to tight junction in colon tissue(P<0.01). Nuciferine could treat obesity through modulating gut microbiota, decreasing gut permeability and ameliorating inflammation.

[Effect of moxibustion at "Zusanli"(ST36) and "Shenshu"(BL23) on miR-155-mediated TLR4/NF-κB signaling involving amelioration of synovitis in rheumatoid arthritis rats].

OBJECTIVE: To explore the effect of moxibustion at "Zusanli"(ST36) and "Shenshu"(BL23) on synovitis, and expressions of miR-155, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), interlukine（IL-1） receptor-associated kinase (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor κB (NF-κB), IL-1ß, tumor necrosis factor receptor (TNF)-α and IL-6 mRNA and protein of synovial membrane in rheumatoid arthritis (RA) rats, so as to explore its mechanism underlying improvement of RA. METHODS: A total of 48 male Wistar rats were randomly divided into normal control, model, moxibustion and antagonist groups (n=12 rats in each group). The RA model was replicated by placing the rats in a wind, cold and wet environment and injection of Freund's complete adjuvant (CFA, 0.5 mL) into the right hindlimb foot plantar. Moxibustion was applied to bilateral ST36 and BL23 for 30 min, once daily for 21 consecutive days. Rats of the antagonist group was treated by injection of TLR4 antagonist (TAK-242, 1 mg/mL, 0.1 mg/kg) via tail vein, once per day for consecutive 21 d. The joint swelling degree (JSD) and arthritis index (AI, red swelling scale) were determined, and the expression levels of various indicators of miR-155, and TLR4, myeloid MyD88, IRAK1, TRAF6, NF-κB, IL-1ß, TNF-α and IL-6 mRNA and protein were assayed by quantitative real time-PCR and Western blot, separately. RESULTS: Compared with the normal control group, the JSD and AI, and the expression levels of synovial miR-155, TLR4, MyD88, IRAK1, TRAF6, NF-κB, IL-1ß, TNF-α and IL-6 mRNA and protein were significantly increased in the model group (P<0.01). Compared with the model group, the increased levels of JSD and AI, and the expression levels of synovial miR-155, TLR4, MyD88, IRAK1, TRAF6, NF-κB, IL-1ß, TNF-α and IL-6 mRNA and protein were notably down-regulated in both moxibustion and antagonist groups (P<0.01). The effects of moxibustion were evidently superior to the antagonist in down-regulating the abovementioned indexes (P<0.01), except TLR4 mRNA and protein. CONCLUSION: Moxibustion at ST36 and BL23 can reduce the synovitis of RA rats, which is related to its effects in suppressing the expressions of miR-155, TLR4, MyD88, IRAK1, TRAF6, NF-κB, IL-1ß, TNF-α and IL-6 mRNA and protein (i.e., inhibition of miR-155/TLR4/NF-κB signaling).

Properties and molecular mechanisms underlying geniposide-mediated therapeutic effects in chronic inflammatory diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Geniposide (GE) is ubiquitous in nearly 40 species of plants, among which Gardenia jasminoides J. Ellis has the highest content, and has been used ethnopharmacologically to treat chronic inflammatory diseases. As a traditional Chinese medicine, Gardenia jasminoides J. Ellis has a long history of usage in detumescence and sedation, liver protection and cholestasis, hypotension and hemostasis. It is commonly used in the treatment of diabetes, hypertension, jaundice hepatitis, sprain and contusion. As a type of iridoid glycosides extracted from Gardenia jasminoides J. Ellis, GE has many pharmacological effects, such as anti-inflammatory, anti-angiogenesic, anti-oxidative, etc. AIM OF THE REVIEW: In this article, we reviewed the sources, traditional usage, pharmacokinetics, toxicity and therapeutic effect of GE on chronic inflammatory diseases, and discussed its potential regulatory mechanisms and clinical application. RESULTS: GE is a common iridoid glycoside in medicinal plants, which has strong activity in the treatment of chronic inflammatory diseases. A large number of in vivo and in vitro experiments confirmed that GE has certain therapeutic value for a variety of chronic inflammation disease. Its mechanism of function is mainly based on its anti-inflammatory, anti-oxidant, neuroprotective properties, as well as regulation of apoptotsis. GE plays a role in the treatment of chronic inflammatory diseases by regulating cell proliferation and apoptosis, realizing the dynamic balance of pro/anti-inflammatory factors, improving the state of oxidative stress, and restoring abnormally expressed inflammation-related pathways. CONCLUSION: According to its extensive pharmacological effects, GE is a promising drug for the treatment of chronic inflammatory diseases.

Unity and separation of lifting-thrusting and twirling reinforcing-reducing manipulation / 中国针灸

To analyze the collaborative use and separation reasons of lifting-thrusting and twirling reinforcing and reducing manipulation. Lifting-thrusting manipulation and twirling manipulation are two important contents of acupuncture methods. In traditional acupuncture and moxibustion, the two methods were used in reinforcing and reducing concert, which was mainly related to the therapeutic thought guided by the

Effect of electroacupuncture at "Neiguan" (PC 6) on cardiac function and inflammatory factors of acupoint area in rats with acute myocardial ischemia / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function and cardiomyocyte apoptosis in rats with acute myocardial ischemia (AMI), and to explore the correlation between myocardial protective effect of EA and inflammatory factors i.e. interleukin-1β (IL-1β) and interleukin-17 (IL-17) of "Neiguan" (PC 6) area.@*METHODS@#A total of 40 male SD rats with normal ultrasonic cardiogram were randomized into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The AMI model was established by ligating the left anterior descending (LAD) branch of the coronary artery in the model group and the EA group, while the threading without ligating was adopted in the sham-operation group and the sham-operation plus EA group. In the sham-operation plus EA group and the EA group, EA at bilateral "Neiguan" (PC 6) was applied, with disperse-dense wave, 2 Hz/100 Hz in frequency and 2 mA in density, once a day, 20 min a time for 3 days. The cardiac ejection fraction (EF) and fractional shortening (FS) were measured by ultrasonic cardiogram to evaluate the cardiac function, the cardiomyocyte apoptosis was detected by TUNEL staining, the infiltration of inflammatory factors of "Neiguan" (PC 6) area was observed by H.E. staining, the expression of inflammatory factors IL-1β and IL-17 of "Neiguan" (PC 6) area was detected by immunofluorescence staining.@*RESULTS@#Compared with the sham-operation group, EF and FS were decreased (@*CONCLUSION@#Electroacupuncture at "Neiguan" (PC 6) can improve the cardiac function and reduce the apoptosis of cardiomyocyte in rats with acute myocardial ischemia, its mechanism may be related to the regulation of the inflammatory factors of "Neiguan" (PC 6) area.

Effect of moxibustion on colonic mucosal injury and expression of CGRP positive nerve fibers of distal colonic mucosa in ulcerative colitis mice / 中国针灸

OBJECTIVE@#To observe the effect of moxibustion at "Zusanli" (ST 36) on distal, middle and proximal colonic mucosal injury and expression of calcitonin gene-related peptide (CGRP) positive nerve fibers of distal colonic mucosa in ulcerative colitis (UC) mice at different time points.@*METHODS@#A total of 51 C57BL/6N mice were randomized into a 7-day control group (@*RESULTS@#Mucosal injury can be observed in mice after modeling, displaying epithelial layer disappearance, abnormal crypt structure or crypt disappearance. Compared with the 7-day control group, colon length was shortened (@*CONCLUSION@#Moxibustion at "Zusanli" (ST 36) can reduce the expressions of positive nerve fibers of colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa, thus, improve the colonic mucosal injury.

Effect of electroacupuncture on expression of IL-23/IL-17 axis and TLR4 in infarcted tissue in rats with myocardial infarction / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on expression of interleukin (IL) -23/IL-17 axis and Toll-like receptor 4 (TLR4) in the infarcted tissue in rats with myocardial infarction (MI), and to explore the mechanism of EA on alleviating MI injury.@*METHODS@#Forty male SD rats were randomly divided into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The MI models were established by ligation of left anterior descending coronary artery in the model group and EA group, while only threading was performed in the sham-operation group and sham-operation plus EA group. The rats in the sham-operation plus EA group and EA group were treated with EA at "Neiguan" (PC 6), disperse-dense wave, 2 Hz/100 Hz, 2 mA, once a day, 20 min each time, for 3 days. After the intervention, the ejection fraction (EF) was measured by echocardiography to evaluate the cardiac function; the infarct area was measured by TTC staining; the HE staining was used to observe the morphological changes of myocardial tissue; the levels of IL-23 and IL-17 in infarcted tissue were detected by ELISA; the protein expression of TLR4 in infarcted tissue was detected by Western blot.@*RESULTS@#Compared with the sham-operation group, the EF was decreased (@*CONCLUSION@#EA may alleviate the excessive inflammatory response after MI by inhibiting the expression of IL-23/IL-17 axis in MI rats, and TLR4 may be involved during the process.

Anti-inflammatory chemical constituents of Flos Chrysanthemi Indici determined by UPLC-MS/MS integrated with network pharmacology.

Flos Chrysanthemi Indici (FCI), the flower of Chrysanthemum indicum L., is a common functional food and a well-known traditional Chinese medicine (TCM) for the treatment of inflammatory diseases. Previous studies have revealed that FCI has anti-inflammatory activity, but little is known about its anti-inflammatory chemical profile. In this study, the potential anti-inflammatory constituents of FCI were investigated by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with the network pharmacology approach, and further confirmed on a LPS activated RAW264.7 macrophage model. As a result, a total of forty-two compounds, including thirty-two flavonoids, nine phenolic acids and one sesquiterpene, were identified. Among them, fourteen compounds including eight flavonoids (11, 17, 24, 28, 32, 39, 41 and 42) and six caffeoylquinic acids (3, 4, 5, 13, 15 and 20) were recognized as potential key anti-inflammatory constituents of FCI through network pharmacology analysis, because they accounted for 92% of the relative peak area in the UPLC-Q-TOF/MS chromatogram and acted on 87 of 97 the inflammatory targets of FCI. However, only 16 targets were shared between the flavonoids and caffeoylquinic acids, indicative of both acting on more different targets. Further the anti-inflammatory effects of the fourteen constituents were validated with the decreased levels of NO, TNF-α, IL-6 and PGE2 in RAW264.7 macrophage cells treated with LPS. Our results indicated that both flavonoids and caffeoylquinic acids were responsible for the anti-inflammatory effect of FCI through synergetic actions on multi-targets. Moreover, 3,5-dicaffeoylquinic acid (15), luteolin (24) and linarin (28) were the most important active constituents of FCI and could be selected as chemical markers for quality control of FCI. Overall, the findings not only explore the anti-inflammatory chemical constituents of FCI, but also provide novel insights into the effective constituents and mechanism of TCMs.

Zinc Therapy Is a Reasonable Choice for Patients With Pressure Injuries: A Systematic Review and Meta-Analysis.

The aim of this systematic review was to summarize the evidence on the efficacy of zinc supplementation in patients with pressure injuries (PIs). Electronic data bases (Embase, MEDLINE, and Web of Science) were searched from inception to 2019 for randomized controlled trials (RCTs) and non-RCTs addressing the efficacy of zinc supplementation compared with a control nutrition invention on PI outcomes. The primary study outcome was the healing rate of PIs during treatment; the secondary outcomes were the improvement of PI area and pressure ulcer scale for healing (PUSH) score. A total of 7 studies were included in this systematic review and meta-analysis. The intervention group significantly had improved healing vs that of the control group (relative risk, 1.44; 95% CI, 1.01-2.06; P = 0.043, I2 = 19.3%). There was no obvious asymmetry in the funnel plot and no strong evidence of publication bias. Sensitivity analysis showed that meta-analysis has good stability. Studies showed a greater mean reduction in PI area. All the studies we included had a significant improvement in the PUSH score of PIs. Our systematic review and meta-analysis from clinical research confirmed that zinc therapy can promote wound healing and suggest that medical staff should consider providing patients with zinc during PI treatment.

Role of biological rhythm dysfunction in the development and management of bipolar disorders: a review.

Disturbance of biological rhythms contributes to the onset of bipolar disorders and is an important clinical feature of the condition. To further explore the role of biological rhythms in bipolar disorders, 95 English articles published between 1968 and 2019 were retrieved from the PubMed database and analysed. We herein review the outcomes of studies on biological rhythm disturbance in bipolar disorders, including the epidemiology, aetiology, clinical features (eg, sleep, feeding and eating disorders) and treatment of the condition evaluated by patients' self-report and biological indicators such as melatonin. Our report supports the characterisation of biological rhythm disturbance as a significant clinical feature affecting the onset and development of bipolar disorders and reviews classical and novel treatments, such as chronotherapy, that can be applied in the clinical practice. Our analysis indicates that a more comprehensive study of the pathophysiology, clinical phenomenology and treatment of biological rhythm disturbance is required.

Real-Time Monitoring of Temperature Variations around a Gold Nanobipyramid Targeted Cancer Cell under Photothermal Heating by Actively Manipulating an Optically Trapped Luminescent Upconversion Microparticle.

We demonstrate an effective approach to realize active and real-time temperature monitoring around the gold nanobipyramids (AuNBPs)-labeled cancer cell under 808 nm laser irradiation by combining optical tweezers and temperature-sensitive upconversion microparticles (UCMPs). On the one hand, the aptamer-modified AuNBPs that absorb laser at 808 nm not only act as an excellent photothermal reagent but also accurately and specifically bind the target cancer cells. On the other hand, the single optically trapped NaYF4:Yb3+, Er3+ UCMPs with a 980 nm laser exhibit temperature-dependent luminescence properties, where the intensity ratio of emission 525 and 547 nm varies with the ambient temperature. Therefore, real-time temperature variation monitoring is performed by 3D manipulation of the trapped single UCMP to control its distance from the AuNBPs-labeled cancer cell while being photothermally killed. The results show distance-related thermal propagation because the temperature increase reaches as high as 10 °C at a distance of 5 µm from the cell, whereas the temperature difference drops rapidly to 5 °C when this distance increases to 15 µm. This approach shows that the photothermal conversion from AuNBPs is sufficient to kill the cancer cells, and the temperature increase can be controlled within the micrometer level at a certain period of time. Overall, we present a micrometer-size thermometer platform and provide an innovative strategy to measure temperature at the micrometer level during photothermal killing of cancer cells.

Influence of Addition and Subtraction Therapy of Zhenwutang to Residual Renal Function and Nutritional Status of Patients with Maintenance Hemodialysis / 中国实验方剂学杂志

Objective:To discuss influence of addition and subtraction therapy of Zhenwutang to residual renal function （RRF）， nutritional status， dialysis adequacy and quality of life of patients with maintenance hemodialysis （MHD）. Method:One hundred and thirty-six patients were randomly divided into control group （68 cases） and observation group （68 cases） by random number table. Patients in two group got MHD， 3 times/week， 4 h/time， levocarnitine injection （1 g dissolved in 5-10 mL water for injection） after the dialysis， 2-3 min/time， recombinant human erythropoietin injection with subcutaneous injection for 4 weeks， 3 000 U， 3 times/day， valsartan capsules for 3 months， 80 mg/time， 1 time/day. The control group took Manshenning mixture， 35 mL / time， 3 times / day.Patients in observation group added addition and subtraction therapy of Zhenwutang for 3 months， 1 dose/day. Before and after treatment， urea nitrogen （BUN）， creatinine （CR） and 24 hours' urine volume were recorded. And RRF， rate of decrease of RRF and rate of decrease in urine volume were also calculated. Levels of hemoglobin （HB）， albumin （ALB）， prealbumin （PA） and transferrin （TRF） were detected. After treatment， standardized protein metabolism rate （nPCR）， urea clearance index （Kt / V） and glomerular filtration rate （EGFR） were discussed. And improved subjective comprehensive nutrition assessment （SGA）， dialysis related quality of life （kdta） and health survey summary （SF-36） were graded. Six months' follow-up， primary end point event （24 h urine volume ≤ 400 mL） and no residual renal function （24 h urine volume ≤ 400 mL） were recorded. Result:Levels of RRF， Kt/V， nPCR， eGFR， Hb， Alb， PA， TRF and total scores of KDTA and SF-36 in observation group were higher than those in control group （P<0.01）. And score of SGA， rate of decrease of RRF and rate of decrease in urine volume were less than those in control group （P<0.01）.Incidence rate of primary end point event was 27.94%（19/68） lower than 47.06%（32/68） in control group （χ2=5.302， P<0.05）， incidence rate of no residual renal functionwas 17.65%（11/68） lower than 36.76%（25/68） in control group （χ2=6.274， P<0.05）. And BUN and Cr were lower than those in control group （P<0.01）， 24 h urine volume was more than that in control group （P<0.01）. Conclusion:Addition and subtraction therapy of Zhenwutang can maintenance of RRF， improvement of nutritional status， improvement of dialysis adequacy and quality of life of patients .