An antibacterial and anti-oxidant hydrogel containing hyperbranched poly-l-lysine and tea polyphenols accelerates healing of infected wound.

Both bacteria-infection and excessive inflammation delay the wound healing process and even create non-healing wound, thus it is highly desirable to endow the wound dressing with bactericidal and anti-oxidation properties. Herein an antibacterial and antioxidation hydrogel based on Carbomer 940 (CBM) and hydroxypropyl methyl cellulose (HPMC) loaded with tea polyphenols (TP) and hyperbranched poly-l-lysine (HBPL) was designed and fabricated. The hydrogel killed 99.9 % of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) at 107 CFU mL-1, and showed strong antioxidation against H2O2 and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH) radicals without noticeable cytotoxicity in vitro. The CBM/HPMC/HBPL/TP hydrogel significantly shortened the inflammatory period of the MRSA-infected full-thickness skin wound of rats in vivo, with 2 orders of lower MRSA colonies compared with the blank control, and promoted the wound closure especially at the earlier stage. The inflammation was suppressed and the vascularization was promoted significantly as well, resulting in reduced pro-inflammatory factors including interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), and increased anti-inflammatory factors such as interleukin-4 (IL-4) and interleukin-10 (IL-10).

Huangqi Guizhi Wuwu decoction alleviates oxaliplatin-induced peripheral neuropathy via the gut-peripheral nerve axis.

BACKGROUND: Oxaliplatin-induced peripheral neurotoxicity (OIPN) limits the dose of chemotherapy and seriously affects the quality of life. Huangqi Guizhi Wuwu Decoction (HGWD) is a classical Traditional Chinese Medicine (TCM) formula for the prevention of OIPN. However, its specific pharmacological mechanism of action remains unknown. Our study found that HGWD can effectively alleviate chronic OIPN and regulate intestinal flora. Therefore, we explored the mechanism of action of HGWD in alleviating chronic OIPN from the perspective of intestinal flora. METHODS: In this study, we established an OIPN model in C57BL/6 mice treated with different concentrations of HGWD. Mechanical pain and cold pain were assessed at certain time points, and samples of mice colon, dorsal root ganglion (DRG), serum, and feces were collected. Associated inflammation levels in the colon and DRG were detected using immunohistochemical techniques; the serum lipopolysaccharide (LPS) levels and associated inflammation were assessed using the appropriate kits; and 16S rRNA sequencing was used to examine the dynamic changes in gut microorganisms. Finally, established fecal microbiota transplantation (FMT) and antibiotic (ABX) pretreatment models were used to validate flora's role in HGWD for chronic OIPN by pain scoring and related pathological analysis. RESULTS: HGWD treatment significantly alleviated pain sensitivity in chronic OIPN mice. Pathological results showed that HGWD treatment improved intestinal ZO-1 expression and reduced serum LPS levels and associated inflammatory factors in the colon, serum, and DRG. The 16S rRNA results showed that HGWD restored the composition of the intestinal flora in a time-dependent manner to alleviate OIPN. FMT and ABX experiments demonstrated that HGWD can alleviate chronic OIPN by regulating intestinal flora homeostasis. CONCLUSIONS: HGWD prevents chronic OIPN by dynamically regulating intestinal flora homeostasis, thereby ameliorating intestinal barrier damage and reducing serum LPS and relevant inflammatory factor levels in the colon, serum, and DRG.

Multifunctional nanoparticles precisely reprogram the tumor microenvironment and potentiate antitumor immunotherapy after near-infrared-II light-mediated photothermal therapy.

Mild-temperature photothermal therapy (mild PTT) is a safe and efficient antitumor therapy. However, mild PTT alone usually fails to activate the immune response and prevent tumor metastasis. Herein, a photothermal agent, copper sulfide@ovalbumin (CuS@OVA), with an effective PTT effect in the second near-infrared (NIR-II) window, is developed. CuS@OVA can optimize the tumor microenvironment (TME) and evoke an adaptive immune response. Copper ions are released in the acidic TME to promote the M1 polarization of tumor-associated macrophages. The model antigen OVA not only acts as a scaffold for nanoparticle growth but also promotes the maturation of dendritic cells, which primes naive T cells to stimulate adaptive immunity. CuS@OVA augments the antitumor efficiency of the immune checkpoint blockade (ICB) in vivo, which suppresses tumor growth and metastasis in a mouse melanoma model. The proposed therapeutic platform, CuS@OVA nanoparticles, may be a potential adjuvant for optimizing the TME and improving the efficiency of ICB as well as other antitumor immunotherapies. STATEMENT OF SIGNIFICANCE: Mild-temperature photothermal therapy (mild PTT) is a safe and efficient antitumor therapy, but usually fails to activate the immune response and prevent tumor metastasis. Herein, we develop a photothermal agent, copper sulfide@ovalbumin (CuS@OVA), with an excellent PTT effect in the second near-infrared (NIR-II) window. CuS@OVA can optimize the tumor microenvironment (TME) and evoke an adaptive immune response by promoting the M1 polarization of tumor-associated macrophages and the maturation of dendritic cells. CuS@OVA augments the antitumor efficiency of the immune checkpoint blockade (ICB) in vivo, suppressing tumor growth and metastasis. The platform may be a potential adjuvant for optimizing the TME and improving the efficiency of ICB as well as other antitumor immunotherapies.

[Effects of different acupuncture and moxibustion methods on articular cartilage morphology and NF-κB p65/NLRP3 pathway in rats with knee osteoarthritis].

OBJECTIVE: To compare the effects of filiform needling, electroacupuncture (EA) and moxibustion on articular cartilage morphology and nuclear transcription factor-κB (NF-κB) p65/ Nod-like receptor protein 3 (NLRP3) pathway in rats with knee osteoarthritis (KOA). METHODS: Wistar rats were randomly divided into blank control， model, filiform needling, EA and moxibustion groups, with 8 rats in each group. The KOA model was established by injecting sodium iodoacetate into the right knee cavity. Filiform needling, EA and moxibustion groups were treated with the right side of "Dubi" (ST35) and "Neixiyan" (EX-LE5), and were given filiform needling, EA and mild moxibustion therapies for 15 min respectively, once every other day, for a total of 4 weeks. The diameter of the right knee joint was observed. The ultrastructure of knee chondrocytes was observed by transmission electron microscope. The contents of serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-18 were determined by ELISA. The expression levels of NF-κB p65, NLRP3, apoptosis-related speckle like protein (ASC) and TNF-α in knee cartilage were dectected by Western blot. RESULTS: Compared with the blank control group, the right knee joint cavity was narrowed, chondrocytes were constricted significantly, mitochondria were moderately swollen, the diameter of the right knee was increased, and the contents of serum TNF-α, IL-1ß and IL-18 were increased (P<0.01), the expressions of NF-κB p65, NLRP3 and TNF-α in knee cartilage were increased (P<0.01) while the expression of ASC was decreased (P<0.01) in the model group.Compared with model group, the narrowed knee joint cavity and chondrocyte injury were improved， knee diameter decreased (P<0.01, P<0.05), and the content of serum TNF-α and the expression of NLRP3 in knee cartilage were decreased (P<0.05, P<0.01) in 3 treatment groups; the contents of serum IL-1ß and IL-18, and the expression of TNF-α in knee cartilage were decreased (P<0.01, P<0.05), while the expression of ASC in knee cartilage was increased (P<0.01) in EA and moxibustion groups; the expression of NF-κB p65 in knee cartilage was decreased (P<0.01) in moxibustion group. Compared with EA group, the content of serum IL-18 was decreased (P<0.05) in moxibustion group. CONCLUSION: Filiform needling, EA and moxibustion can all reduce the formation of knee osteophytosis in KOA rats, alleviate joint cavity narrowing, improve the ultrastructure of articular cartilage, reduce the level of inflammatory factors, regulate the NF-κB p65/NLRP3 pathway. Moxibustion has the most obvious regulatory effect among the 3 treatment methods.

Precisely Tuning the Pore-Wall Surface Composition of Bioceramic Scaffolds Facilitates Angiogenesis and Orbital Bone Defect Repair.

Orbital bone damage (OBD) may result in severe post-traumatic enophthalmos, craniomaxillofacial deformities, vision loss, and intracranial infections. However, it is still a challenge to fabricate advanced biomaterials that can match the individual anatomical structure and enhance OBD repair in situ. Herein, we aimed to develop a selective surface modification strategy on bioceramic scaffolds and evaluated the effects of inorganic or organic functional coating on angiogenesis and osteogenesis, ectopically and orthotopically in OBD models. It was shown that the low thermal bioactive glass (BG) modification or layer-by-layer assembly of a biomimetic hydrogel (Biogel) could readily integrate into the pore wall of the bioceramic scaffolds. The BG and Biogel modification showed appreciable enhancement in the initial compressive strength (∼30-75%) or structural stability in vivo, respectively. BG modification could enhance by nearly 2-fold the vessel ingrowth, and the osteogenic capacity was also accelerated, accompanied with a mild scaffold biodegradation after 3 months. Meanwhile, the Biogel-modified scaffolds showed enhanced osteogenic differentiation and mineralization through calcium and phosphorus retention. The potential mechanism of the enhanced bone repair was elucidated via vascular and osteogenic cell responses in vitro, and the cell tests indicated that the Biogel and BG functional layers were both beneficial for in vitro osteoblastic differentiation and mineralization on bioceramics. Totally, these findings demonstrated that the bioactive ions or biomolecules could significantly improve the angiogenic and osteogenic capabilities of conventional bioceramics, and the integration of inorganic or organic functional coating in the pore wall is a highly flexible material toolbox that can be tailored directly to improve orbital bone defect repair.

Qingchang Wenzhong Decoction Prevents the Occurrence of Intestinal Tumors by Regulating Intestinal Microbiota and Gasdermin E.

Background: Intestinal tumors are the third most common malignant tumors worldwide, accounting for approximately 10% of all new cancer cases worldwide. Cancer prevention is a promising way to limit the intestinal tumor incidence rate; however, challenges remain. Qingchang Wenzhong decoction (QCWZD) can clinically treat mild to moderate ulcerative colitis symptoms. Moreover, the mechanism by which it prevents intestinal tumors has not been clarified. In this study, we explored the mechanism by which QCWZD prevents the occurrence of intestinal tumors. Methods: To study the preventive mechanism of QCWZD on intestinal tumors, we used two model mice with azoxymethane/dextran sodium sulfate (AOM/DSS)- and Apcmin/+-induced intestinal tumor formation. The two models exhibited colitis-associated cancer and familial adenomatous polyposis, respectively. Colon and small intestine tissues were collected and analyzed based on histopathology and immunohistochemistry analyses. Fecal samples were collected, and 16S rRNA sequencing was used to analyze the correlation between intestinal microbiota and the prevention of intestinal tumors. Results: In the AOM/DSS mice, the QCWZD reduced the number and size of tumors, as well as tumor load. Similarly, in the Apcmin/+ mice, QCWZD can also reduce the number of tumors and the tumor load. The results of 16S rRNA sequencing confirmed that QCWZD altered the composition of intestinal microbiota in mice, a phenomenon that may prevent the occurrence of intestinal tumors by aiding the increase in the abundance of beneficial bacteria, such as Ralstonia and Butyricicoccus, and reducing that of pathogenic bacteria, such as Desulfobacterota and Bacteroides, in the intestine. Further, immunohistochemistry reveald that QCWZD can improve the expression of intestinal barrier-related proteins and inhibit pyroptosis-related proteins. Conclusions: QCWZD has the potential to prevent the occurrence of intestinal tumors. The anti-tumor activity may be achieved by regulating the intestinal microbiota, improving the function of the intestinal barrier, and inhibiting GSDME mediated pyroptosis.

Effects of different courses of moxibustion treatment on intestinal flora and inflammation of a rat model of knee osteoarthritis.

OBJECTIVE: This study was done to determine the effects of different courses of moxibustion on a rat knee osteoarthritis (KOA) model, and explore the dose-effect relationship of moxibustion on KOA from the perspectives of intestinal flora and inflammatory factors. METHODS: Wistar rats were randomly divided into five groups: normal, model, moxibustion for 2 weeks, moxibustion for 4 weeks and moxibustion for 6 weeks groups (n = 5 each group). A KOA rat model was induced by monosodium iodoacetate, and moxibustion intervention was performed at the acupoints "Dubi" (ST35) and "Zusanli" (ST36), once every other day. Pathologic changes in the cartilage of rat knee joints were assessed after intervention, and fecal samples were subjected to 16S rRNA high-throughput sequencing for microbial diversity analysis. RESULTS: Damage to the knee articular cartilage was obvious in the model group, which also had increased levels of pro-inflammatory factors, decreased levels of anti-inflammatory factors, and intestinal flora disorders with decreased diversity. The degree of cartilage damage in the 4 and 6 weeks of moxibustion groups was significantly improved compared with the model group. The 4 and 6 weeks of moxibustion groups also demonstrated reduced levels of interleukin-1ß and tumor necrosis factor-α and increased levels of interleukin-10 (P < 0.05). Both the abundance and diversity of the intestinal flora were increased, approaching those of the normal group. Abundances of probiotics Eubacterium coprostanoligenes group and Ruminococcaceae UCG-014 increased, while that of the pathogenic bacteria Lachnospiraceae NK4A136 group decreased (P < 0.05). Although the abundance of Lachnospiraceae NK4A136 group decreased in the 2 weeks of moxibustion group compared with the model group (P < 0.05), there was no statistically significant difference in serum inflammatory factors, flora species diversity or degree of pathological damage compared with the model group. CONCLUSION: Moxibustion treatment led to significant improvements in the intestinal flora and inflammatory factors of rats with KOA. Moxibustion treatment of 4 and 6 weeks led to better outcomes than the 2-week course. Moxibustion for 4 and 6 weeks can regulate intestinal flora dysfunction with increased probiotics and reduced pathogenic bacteria, reduce pro-inflammatory factors and increase anti-inflammatory factors. No significant differences were seen between the effects of moxibustion for 4 weeks and 6 weeks.

Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages.

BACKGROUND: Stimulator of IFN genes (STING) is highly expressed in the livers of non-alcoholic fatty liver disease (NAFLD) patients and high fat diet (HFD) induced NAFLD mice model. The STING signaling-mediated inflammation has been shown to play a critical role in metabolic disorders. Lingguizhugan decoction (LGZG), a Traditional Chinese herbal decoction, has been applied to treat metabolic disorders for many years. However, whether LGZG can alleviate the progression of NAFLD through inhibiting inflammation remains unclear. This study was to determine the role of STING-mediated inflammation in the HFD-induced hepatic-lipid deposition treated with LGZG. METHODS: The anti-inflammatory and anti-steatotic effects of LGZG in vivo were detected by H&E staining, immunofluorescence and immuno-chemistry. Mice bone-marrow-derived macrophages (BMDMs) and primary liver macrophages were treated with STING-specific agonist (DMXAA), LGZG and its critical components respectively. The treated culture supernatant of BMDMs and primary liver macrophages from each group was co-cultured with palmitic acid-treated mouse primary hepatocytes or mouse liver cell line AML-12 respectively to detect whether the activation of STING-mediated pathway is involved in the anti-steatotic effect of LGZG. The hepatocyte lipid deposition in vivo and in vitro were detected by oil red staining. Mitochondrial DNA release of mouse liver extracts were detected by real time PCR. The expression of proteins and inflammatory cytokines related to STING-TBK1-NF-κB pathway was detected by western blotting and ELISA. RESULTS: LGZG significantly ameliorated HFD induced hepatic steatosis, oxidative stress, hepatic mitochondrial damage and mitochondrial DNA release, which was correlated with reduction of the expression level of STING as well as the infiltration of STING-positive macrophages in the livers of HFD fed mice. The critical components of LGZG directly inhibited the activation of STING-TBK1-NF-κB pathway in liver macrophages induced by DMXAA, LPS, thereby reducing the release of IFNß and TNFα. Co-incubating the culture supernatant of LGZG treated liver macrophages and PA-stimulated hepatocytes significantly inhibited the PA-induced lipid deposition. CONCLUSION: This study demonstrates that LGZG can ameliorate HFD-induced hepatic-lipid deposition through inhibiting STING-TBK1-NF-κB pathway in liver macrophages, which provides novel insight for elucidating the molecular mechanism of LGZG alleviating HFD induced hepatic steatosis.

Makatoxin-3, a thermostable Nav1.7 agonist from Buthus martensii Karsch (BmK) scorpion elicits non-narcotic analgesia in inflammatory pain models.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic pain management represents a serious healthcare problem worldwide. The use of opioid analgesics for pain has always been hampered by their side effects; in particular, the addictive liability associated with chronic use. Finding a morphine replacement has been a long-standing goal in the field of analgesia. In traditional Chinese medicine, processed Buthus martensii Karsch (BmK) scorpion has been used as a painkiller to treat chronic inflammatory arthritis and spondylitis, so called "Scorpio-analgesia". However, the molecular basis and the underline mechanism for the Scorpio-analgesia are still unclear. AIM OF THE STUDY: The study aims to investigate the molecular basis of "Scorpio analgesia" and identify novel analgesics from BmK scorpion. MATERIALS AND METHODS: In this study, the analgesic abilities were determined using formalin-, acetic acid- and complete Freund's adjuvant-induced pain models. The effect of BmK venom and processed BmK venom on Nav1.7 were detected by whole-cell voltage-clamp recordings on HEK293-hNav1.7 stable cell line. Action potentials in Dorsal root ganglion (DRG) neurons induced by Makatoxin-3-R58A were recorded in current-clamp mode. The content of Makatoxin-3 was detected using competitive enzyme-linked immunosorbent assay based on the Makatoxin-3 antibody. High performance liquid chromatography, western blot and circular dichroism spectroscopy were used to analysis the stability of Makatoxin-3. RESULTS: Here we demonstrate that Makatoxin-3, an α-like toxin in BmK scorpion venom targeting Nav1.7 is the critical component in Scorpio-analgesia. The analgesic effect of Makatoxin-3 could not be reversed by naloxone and is more potent than Nav1.7-selective inhibitors and non-steroidal anti-inflammatory drugs in inflammatory models. Moreover, a R58A mutant of Makatoxin-3 is capable of eliciting analgesia effect without inducing pain response. CONCLUSIONS: This study advances ion channel biology and proposes Nav1.7 agonists, rather than the presumed Nav1.7-only blockers, for non-narcotic relief of chronic pain.

Effects of different courses of moxibustion treatment on intestinal flora and inflammation of a rat model of knee osteoarthritis / 中西医结合学报

OBJECTIVE@#This study was done to determine the effects of different courses of moxibustion on a rat knee osteoarthritis (KOA) model, and explore the dose-effect relationship of moxibustion on KOA from the perspectives of intestinal flora and inflammatory factors.@*METHODS@#Wistar rats were randomly divided into five groups: normal, model, moxibustion for 2 weeks, moxibustion for 4 weeks and moxibustion for 6 weeks groups (n = 5 each group). A KOA rat model was induced by monosodium iodoacetate, and moxibustion intervention was performed at the acupoints "Dubi" (ST35) and "Zusanli" (ST36), once every other day. Pathologic changes in the cartilage of rat knee joints were assessed after intervention, and fecal samples were subjected to 16S rRNA high-throughput sequencing for microbial diversity analysis.@*RESULTS@#Damage to the knee articular cartilage was obvious in the model group, which also had increased levels of pro-inflammatory factors, decreased levels of anti-inflammatory factors, and intestinal flora disorders with decreased diversity. The degree of cartilage damage in the 4 and 6 weeks of moxibustion groups was significantly improved compared with the model group. The 4 and 6 weeks of moxibustion groups also demonstrated reduced levels of interleukin-1β and tumor necrosis factor-α and increased levels of interleukin-10 (P < 0.05). Both the abundance and diversity of the intestinal flora were increased, approaching those of the normal group. Abundances of probiotics Eubacterium coprostanoligenes group and Ruminococcaceae UCG-014 increased, while that of the pathogenic bacteria Lachnospiraceae NK4A136 group decreased (P < 0.05). Although the abundance of Lachnospiraceae NK4A136 group decreased in the 2 weeks of moxibustion group compared with the model group (P < 0.05), there was no statistically significant difference in serum inflammatory factors, flora species diversity or degree of pathological damage compared with the model group.@*CONCLUSION@#Moxibustion treatment led to significant improvements in the intestinal flora and inflammatory factors of rats with KOA. Moxibustion treatment of 4 and 6 weeks led to better outcomes than the 2-week course. Moxibustion for 4 and 6 weeks can regulate intestinal flora dysfunction with increased probiotics and reduced pathogenic bacteria, reduce pro-inflammatory factors and increase anti-inflammatory factors. No significant differences were seen between the effects of moxibustion for 4 weeks and 6 weeks.

[Protective effect and mechanism of Wangshi Baochi Pills against acute alcoholic liver/stomach injury in mice].

As a common disease worldwide, alcoholic liver injury is caused by long-term or excessive intake of alcohol and triggers cell death due to alcohol metabolism and reactive oxygen species(ROS)-mediated cytotoxicity. Wangshi Baochi(WSBC) Pills have been widely adopted in clinical practice for evacuating stasis, resolving turbidity, clearing heat, tranquilizing mind, invigorating sto-mach, promoting digestion, purging fire and removing toxin. This study aimed to investigate the efficacy of WSBC Pills in dispelling the effect of alcohol and protecting against acute alcoholic liver/stomach injury in mice, and preliminarily investigate its possible mole-cular mechanism. The results found that the preventive treatment with WSBC Pills contributed to elevating the activity of alcohol dehydrogenase(ADH) and its expression in liver and shortening the time required for sobering up of mice with acute alcoholic liver injury. The staining of liver pathological sections as well as the detection of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and liver ROS levels revealed that WSBC Pills protected the liver by reducing serum AST and ALT. It suppressed oxidative stress-induced liver injury by lowering liver ROS and elevating superoxide dismutase(SOD), and the liver-protecting effect was superior to that of silibinin. Western blot assay confirmed that WSBC Pills inhibited the oxidative stress by up-regulating SOD1 and NAD(P)H: quinone oxidoreductase 1(NQO-1). In addition, WSBC Pills lowered the ROS level to protect against the acute alcoholic stomach injury in mice. The findings have suggested that WSBC Pills alleviated the acute alcoholic liver/stomach injury in mice by increasing ADH and resisting oxidative stress.

[Effect of moxibustion on inflammatory factors and oxidative stress factors in patients with knee osteoarthritis: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between moxibustion and acupuncture for knee osteoarthritis (KOA), and to observe the effect on serum tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), superoxide dismutase (SOD) and malondialdehyde (MDA). METHODS: A total of 60 patients with KOA were randomized into a moxibustion group (30 cases, 2 cases dropped off) and an acupuncture group (30 cases, 2 cases dropped off). In the aucpuncture group, acupuncture was applied at Neixiyan (EX-LE 4), Dubi (ST 35), Heding (EX-LE 2), Xuehai (SP 10), Liangqiu (ST 34), Zusanli (ST 36) and ashi point on the affected side for 30 min.In the moxibustion group, moxibustion was adopted at knee for 60 min. The treatment was given once every two days for 4 weeks, totally 14 times. Before and after treatment, the western ontario and McMaster universities osteoarthritis index (WOMAC) score was compared, and the therapeutic effect was evaluated in the two groups. The contents of serum TNF-αand IL-1ß, the activity of serum SOD and the serum level of MDA were detected in the two groups. RESULTS: Compared before treatment, the WOMAC scores and the contents of serum TNF-α, IL-1ß and MDA after treatment were reduced (P<0.05), the activity of serum SOD was increased (P<0.05) in the two groups. In the moxibustion group, the WOMAC score and the contents of serum TNF-α, IL-1ß and MDA after treatment were lower than the acupuncture group (P<0.05), the activity of serum SOD was higher than the acupuncture group (P<0.05). The total effective rate was 89.3% (25/28) in the moxibustion group, which was superior to 42.9% (12/28) in the acupuncture group (P<0.05). CONCLUSION: Moxibustion and acupuncture can relieve KOA symptoms, and the therapeutic effect of moxibustion is superior to acupuncture. The mechanism may be related to the reduction of serum inflammatory factor and oxidative stress factor.

[Clinical application characteristics of different acupuncture-moxibustion therapies for knee osteoarthritis in the past decade: an analysis based on data mining techniques].

OBJECTIVE: To investigate the application characteristics of different acupuncture-moxibusition (acu-moxi) therapies for knee osteoarthritis (KOA), and to provide a reference for clinical application. METHODS: Computer and data mining techniques were used to establish a database of acu-moxi therapies for KOA, and the articles on acu-moxi in the treatment of KOA in the past decade were collected, screened, entered, reviewed, and analyzed. Acu-moxi therapies for KOA were summarized in terms of treatment method, clinical effect, association between treatment method and acupoint selection, needle specifications, and depth of acupuncture. RESULTS: There are as many as 46 kinds of operation methods to treat knee osteoarthritis, among which moxibustion method has the highest frequency and the most operation methods. Traditional Chinese acupuncture and moxibustion technology has a significant effect on knee osteoarthritis, and the effective rate is more than 90%, among which the minimally invasive technique of traditional Chinese medicine has the highest cure rate and recovery rate. The relationship between traditional Chinese medicine operation and acupoint selection shows that the acupuncture and moxibustion therapy guided by traditional Chinese medicine theory pays more attention to acupoint selection based on syndrome differentiation, while the minimally invasive technique of traditional Chinese medicine is mostly proximal acupoint selection. The diameter of the needle with the highest usage frequency was 0.3 mm. The larger the diameter of the needle, the higher the specificity. The level of acupuncture was mostly tendon, followed by bone. The cure rate of acupuncture to bone is the highest. CONCLUSION: Acupuncture and moxibustion has a significant effect in the treatment of KOA, with a profound theoretical basis; treatment of KOA should emphasize overall conditioning, and acupuncture should reach the bone and the tendon, so as to achieve a better clinical effect.

[Comparision of therapertic effect of different acupuncture methods for knee osteoarthritis].

OBJECTIVE: To compare the clinical efficacy of acupuncture, electroacupuncture (EA) and moxibustion in the treatment of knee osteoarthritis (KOA). METHODS: A total of eight-four patients with KOA were randomly and equally divided into acupuncture group, EA group and moxibustion group. Neixiyan (EX-LE40), Dubi (ST35), Heding (EX-LE2), Liangqiu (ST34), Xuehai (SP10), Zusanli (ST36) and Ashi-point on the affected side of the body were punctured with filiform needles or EA (2 Hz/100 Hz) for 30 min. In the moxibustion group, moxibustion was applied to the surrounding area of the affected joint for 60 min. The treatment was conducted once every other day for 4 weeks. The pain degree was assessed by using numerical rating scale (NRS) and the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) scale (0－240 points) was used to evaluate the severity of KOA. The "Minimal Clinically Important Improvement (MCII)" was used to assess the therapeutic effect after the treatment. RESULTS: After the treatment, the scores of NRS, and the pain, stiffness, motor function and total scores of WOMAC were significantly decreased in the three groups compared with their own pre-treatment (P<0.05), and were obviously lower in the EA and moxibustion groups than in the acupuncture group (P<0.05), and those of the moxibustion group was notably lower than those of the acupuncture group (P<0.05). Of the 28 cases in the acupuncture, EA and moxibustion groups, 11, 17 and 22 were effective, with the effective rate being 39.29%, 60.71% and 78.57%, respectively. The comprehensive therapeutic effect of the moxibustion group was significantly superior to that of the acupuncture and EA groups (P<0.05). CONCLUSION: All the three different kinds of acupuncture and moxibustion methods have positively regulatory effect on KOA, and moxibustion is the best for reducing the joint pain and stiffness, and improving the motor function.

[Feasibility analysis on acupuncture therapy for the treatment of Corona Virus Disease 2019 and the exploration on the application scheme].

The situation of Corona Virus Disease 2019 (COVID-19) is still severe at present. In order to better fight against the epidemic and give full play to the advantages of traditional Chinese medicine, we explored the feasibility of acupuncture therapy in the intervention of COVID-19 through analyzing the relevant literature in both ancient and modern time. Additionally, we analyzed the intervention scheme of acupuncture for COVID-19 developed by China Association of Acupuncture and Moxibustion and supplemented the protocol of the intervention with auricular acupuncture. It was proposed that the advantages of acupuncture and moxibustion should be fully displayed while Chinese herbal medications have been applied in the treatment of COVID-19. During treatment, acupuncture physicians should be rationally allocated to a certain proportion so as to adequately utilize comprehensive therapeutic approaches and guarantee people's safety to the greatest extent. Eventually, the clinical therapeutic effect may be improved, the national resources be economized on and the COVID-19 epidemic be conquered early.

Arnebiae Radix prevents atrial fibrillation in rats by ameliorating atrial remodeling and cardiac function.

ETHNOPHARMACOLOGICAL RELEVANCE: Arnebiae Radix, a common herbal medicine in China, is often utilized to treat blood-heat syndrome and has been reported to exert an effect on the heart. AIM OF THE STUDY: The combination of acetylcholine (Ach) and CaCl2 has been widely used to induce atrial fibrillation (AF) in animals. However, whether Arnebiae Radix displays any preventive action on Ach-CaCl2 induced AF in rats remains uncertain. In our study, we attempted to investigate the protective effects of Arnebiae Radix on Ach-CaCl2 induced AF compared to amiodarone, which was employed as the positive control. MATERIALS AND METHODS: To establish the AF model, SD rats were treated with a mixture of 0.1 mL/100 g Ach-CaCl2 (60 µg/mL Ach and 10 mg/mL CaCl2) by tail vein injection for 7 days. Rats were also given a gavage of Arnebiae Radix (0.18 g/mL) one week before or concurrently with the establishment of the AF model. At the end of the experimental period, the induction, duration and timing of AF were monitored using electrocardiogram recordings. Left atrial tissues were stained to observe the level of fibrosis. Electrophysiological measurements were used to examine atrial size and function. RESULTS: In Ach-CaCl2-induced AF rats, Arnebiae Radix decreased AF induction, duration and susceptibility to AF. In addition, Arnebiae Radix significantly reduced atrial fibrosis and inhibited atrial enlargement induced by Ach-CaCl2. Moreover, there was an apparent improvement in cardiac function in the Arnebiae Radix-treated group. CONCLUSIONS: Our findings indicate that Arnebiae Radix treatment can attenuate Ach-CaCl2-induced atrial injury and serve as an effective therapeutic strategy for the treatment of AF in the future.

Effect of moxibustion on inflammatory factors and oxidative stress factors in patients with knee osteoarthritis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical efficacy between moxibustion and acupuncture for knee osteoarthritis (KOA), and to observe the effect on serum tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), superoxide dismutase (SOD) and malondialdehyde (MDA).@*METHODS@#A total of 60 patients with KOA were randomized into a moxibustion group (30 cases, 2 cases dropped off) and an acupuncture group (30 cases, 2 cases dropped off). In the aucpuncture group, acupuncture was applied at Neixiyan (EX-LE 4), Dubi (ST 35), Heding (EX-LE 2), Xuehai (SP 10), Liangqiu (ST 34), Zusanli (ST 36) and point on the affected side for 30 min.In the moxibustion group, moxibustion was adopted at knee for 60 min. The treatment was given once every two days for 4 weeks, totally 14 times. Before and after treatment, the western ontario and McMaster universities osteoarthritis index (WOMAC) score was compared, and the therapeutic effect was evaluated in the two groups. The contents of serum TNF-αand IL-1β, the activity of serum SOD and the serum level of MDA were detected in the two groups.@*RESULTS@#Compared before treatment, the WOMAC scores and the contents of serum TNF-α, IL-1β and MDA after treatment were reduced (<0.05), the activity of serum SOD was increased (<0.05) in the two groups. In the moxibustion group, the WOMAC score and the contents of serum TNF-α, IL-1β and MDA after treatment were lower than the acupuncture group (<0.05), the activity of serum SOD was higher than the acupuncture group (<0.05). The total effective rate was 89.3% (25/28) in the moxibustion group, which was superior to 42.9% (12/28) in the acupuncture group (<0.05).@*CONCLUSION@#Moxibustion and acupuncture can relieve KOA symptoms, and the therapeutic effect of moxibustion is superior to acupuncture. The mechanism may be related to the reduction of serum inflammatory factor and oxidative stress factor.

Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth.

BACKGROUND: It is unclear whether plant-derived extracellular vesicles (EVs) can mediate interspecies communication with mammalian cells. Tumor-associated macrophages (TAMs) display a continuum of different polarization states between tumoricidal M1 phenotype and tumor-supportive M2 phenotypes, with a lower M1/M2 ratio correlating with tumor growth, angiogenesis and invasion. We investigated whether EVs from ginseng can alter M2-like polarization both in vitro and in vivo to promote cancer immunotherapy. METHODS: A novel EVs-liked ginseng-derived nanoparticles (GDNPs) were isolated and characterized from Panax ginseng C. A. Mey. Using GDNPs as an immunopotentiator for altering M2 polarized macrophages, we analyzed associated surface markers, genes and cytokines of macrophages treated with GDNPs. Mice bearing B16F10 melanoma were treated with GDNPs therapy. Tumor growth were assessed, and TAM populations were evaluated by FACS and IF. RESULTS: GDNPs significantly promoted the polarization of M2 to M1 phenotype and produce total reactive oxygen species, resulting in increasing apoptosis of mouse melanoma cells. GDNP-induced M1 polarization was found to depend upon Toll-like receptor (TLR)-4 and myeloid differentiation antigen 88 (MyD88)-mediated signaling. Moreover, ceramide lipids and proteins of GDNPs may play an important role in macrophage polarization via TLR4 activation. We found that GDNPs treatment significantly suppressed melanoma growth in tumor-bearing mice with increased presence of M1 macrophages detected in the tumor tissue. CONCLUSIONS: GDNPs can alter M2 polarization both in vitro and in vivo, which contributes to an antitumor response. The polarization of macrophages induced by GDNPs is largely dependent on TLR4 and MyD88 signalling. GDNPs as an immunomodulator participate in mammalian immune response and may represent a new class of nano-drugs in cancer immunotherapy.

[Regularities of clinical application of hand acupuncture therapy to treatment of various diseases based on data mining].

OBJECTIVE: To explore the regularities of clinical application of hand acupuncture therapy to the treatment of diseases of different departments by using data mining technique, so as to provide a reference for clinical practice. METHODS: We searched papers, academic dissertations and case reports (published in journals from Jan 1, 1953 to December 31, 2017) from databases of China National Knowledge Internet (CNKI), VIP, and Wanfang, and also searched papers from medical books about hand acupuncture treatment of different diseases/illness by using keywords of "hand acupuncture" and "hand acupoints"， followed by constructing a database after sorting, screening, recording, extracting, and statistical analysis by using a computer. Then, the data mining was conducted for summarizing the characteristics and rules of the hand acupuncture therapy in clinical application. RESULTS: The hand acupuncture therapy in Chinese medical journals was found to be applied to various clinical departments, with the frequency from high to low successively being 16 types of diseases (37.21%) in the surgery, 15 diseases (34.88%) in the internal medicine, 2 diseases (4.65%) in the pediatrics, 8 diseases (18.60%) in the ophthalmology-otorhinolaryngology, 1 disease (2.33%) in the genecology and 1 disease (2.33%) in the dermatology. In the treatment of diseases, the cure plus markedly effective rate of hand acupuncture was found to be highest for diseases of the pediatrics (90.65%), and was 88.45% surgery, 78.06% internal medicine, 89.96% ophthalmology-otorhinolaryngology, 60.61% gynecology, and 67.73% dermatology, respectively. When hand acupuncture used, the acupoints of the hand region on both sides, healthy side and affected side were often selected, and movement exercise was often used in combination, particularly for problems of the surgery. In the collected medical records and 6 acupuncture books, the hand acupuncture was employed for treatment of 34 and 123 kinds of diseases or problems, respectively, with the tissue injury, lumbocrural pain being most frequently seen in the records, and abdominal pain, lumbocrural, chest obstruction, etc. most frequently seen in the acupuncture books. CONCLUSION: Hand acupuncture therapy is widely used in the treatment of many clinical problems of different departments, such as tissue injury, leg pain, etc. of the surgery; abdominal pain, asthma, etc. of the internal medicine; infantile enuresis, diarrhea, etc. of the pediatrics. Acupoints of the hand on the unilateral side are frequently employed and may have a better therapeutic effect.

Regularities of clinical application of hand acupuncture therapy to treatment of various diseases based on data mining / 针刺研究

OBJECTIVE: To explore the regularities of clinical application of hand acupuncture therapy to the treatment of diseases of different departments by using data mining technique, so as to provide a reference for clinical practice. METHODS: We searched papers, academic dissertations and case reports (published in journals from Jan 1, 1953 to December 31, 2017) from databases of China National Knowledge Internet (CNKI), VIP, and Wanfang, and also searched papers from medical books about hand acupuncture treatment of different diseases/illness by using keywords of "hand acupuncture" and "hand acupoints"， followed by constructing a database after sorting, screening, recording, extracting, and statistical analysis by using a computer. Then, the data mining was conducted for summarizing the characteristics and rules of the hand acupuncture therapy in clinical application. RESULTS: The hand acupuncture therapy in Chinese medical journals was found to be applied to various clinical departments, with the frequency from high to low successively being 16 types of diseases (37.21%) in the surgery, 15 diseases (34.88%) in the internal medicine, 2 diseases (4.65%) in the pediatrics, 8 diseases (18.60%) in the ophthalmology-otorhinolaryngology, 1 disease (2.33%) in the genecology and 1 disease (2.33%) in the dermatology. In the treatment of diseases, the cure plus markedly effective rate of hand acupuncture was found to be highest for diseases of the pediatrics (90.65%), and was 88.45% surgery, 78.06% internal medicine, 89.96% ophthalmology-otorhinolaryngology, 60.61% gynecology, and 67.73% dermatology, respectively. When hand acupuncture used, the acupoints of the hand region on both sides, healthy side and affected side were often selected, and movement exercise was often used in combination, particularly for problems of the surgery. In the collected medical records and 6 acupuncture books, the hand acupuncture was employed for treatment of 34 and 123 kinds of diseases or problems, respectively, with the tissue injury, lumbocrural pain being most frequently seen in the records, and abdominal pain, lumbocrural, chest obstruction, etc. most frequently seen in the acupuncture books. CONCLUSION: Hand acupuncture therapy is widely used in the treatment of many clinical problems of different departments, such as tissue injury, leg pain, etc. of the surgery; abdominal pain, asthma, etc. of the internal medicine; infantile enuresis, diarrhea, etc. of the pediatrics. Acupoints of the hand on the unilateral side are frequently employed and may have a better therapeutic effect.