Ponicidin inhibited gallbladder cancer proliferation and metastasis by decreasing MAGEB2 expression through FOXO4.

BACKGROUND: Gallbladder cancer (GBC) is the most aggressively malignant tumor in the bile duct system. The prognosis for patients with GBC is extremely poor. Ponicidin is a diterpenoid compound extracted and purified from the traditional Chinese herb Rabdosia rubescens, and showed promising anti-cancer effects in a variety of tumors. However, Ponicidin has not been investigated in GBC. METHODS: CCK-8, colony formation assay and EdU-488 DNA synthesis assay were performed to investigate the effect of Ponicidin on GBC cells proliferation. Cell invasion and migration assays and wound-healing assay were used to explore the effect of Ponicidin on invasion and migration ability of GBC cells. mRNA-seq was adopted to explore the underlying mechanisms. Western blot and immunohistochemical staining were conducted to detect the protein level. CHIP assay and dual-luciferase assay were used to validate binding motif. Nude mouse model of GBC was used to assess the anti-tumor effect and safety of Ponicidin. RESULTS: Ponicidin inhibited the proliferation and cell invasion and migration of GBC cells in vitro. Moreover, Ponicidin exerted anti-tumor effects by down-regulating the expression of MAGEB2. Mechanically, Ponicidin upregulated the FOXO4 expression and promoted it to accumulate in nucleus to inhibit the transcript of MAGEB2. Furthermore, Ponicidin suppressed tumor growth in the nude mouse model of GBC with excellent safety. CONCLUSION: Ponicidin may be a promising agent for the treatment of GBC effectively and safely.

[Effect of moxibustion on quality of life in tumor patients: network Meta-analysis].

OBJECTIVE: To rank the effectiveness of various moxibustion methods on the quality of life in tumor patients, and explore the best treatment plan of moxibustion for improving the quality of life in tumor patients from the perspective of evidence-based medicine. METHODS: The Chinese and English literature of randomized controlled trial (RCT) of the effect of moxibustion on the quality of life in tumor patients were searched in PubMed, EMbase, Cochrane Library, CNKI, SinoMed, Wanfang and VIP. The retrieval time was from the establishment of the databases to October 31, 2020. The R3.6.2 and Stata15.0 software were used for network Meta-analysis based on Bayesian model. RESULTS: A total of 30 Chinese RCTs were included, including 2 169 patients, involving 16 interventions. In terms of the effectiveness of improving quality of life, the top three treatments were special moxibustion plus other therapies 1 (either of tendon acupuncture, acupoint pressing, acupoint injection, etc.), wheat-grain moxibustion and mild moxibustion. The special moxibustion methods were the combination of fire-dragon moxibustion, thunder-fire moxibustion, fuyang fire moxibustion and moxa salt-bag moxibustion. The number of literature of these four moxibustion methods was small. Considering the clinical application of moxibustion, it was concluded that wheat-grain moxibustion ranked first. CONCLUSION: The adjuvant treatment of wheat-grain moxibustion is more effective than other moxibustion methods on improving the quality of life in tumor patients, but the results needed to be further verified because the bias risk of RCT included in this study is high and the sample size is small.

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.

Direct contact moxibustion promotes apoptosis of gastric cancer cells in rats by regulating intestinal flora.

OBJECTIVE: To examine whether direct contact moxibustion (DCM) can prevent and treat gastric cancer (GC) by regulating intestinal flora in rats. METHODS: Male Wistar rats were randomly divided into normal group, normal + DCM control group, model group, and model + DCM group. Gastric cancer rats were induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG, 20 mg/mL) by gavage. At the same time, the model rats and normal rats were given DCM at Zusanli (ST36), Weishu (BL21), and Zhongwan (CV12) for 16 weeks. After treatment, gastric tissues were collected to analyze the pathological changes and the apoptosis of gastric mucosa cells. In addition, the cecal stool was taken and analyzed by 16s rRNA sequencing. RESULTS: Gastric cancer-like pathological changes and different abundance of the intestinal flora were found in the model group. DCM promoted mucosa tissue apoptosis and regulated the abnormal changes of the intestinal microflora caused by MNNG; DCM also inhibited the growth of Ruminococcaceae and Prevotellaceae flora and promoted the growth of probiotic Akkermansia. Furthermore, DCM made the composition and abundance of intestinal microflora in the GC rats tending to the normal rats. CONCLUSION: DCM stimulating Zusanli (ST36), Weishu (BL21), and Zhongwan (CV12) promoted the apoptosis of gastric mucosa and delayed the progression of gastric cancer, possibly by decreasing Ruminococcaceae and Prevotellaceae bacteria (bacteria that produce short-chain fatty acids in the intestine) and promoting the growth of probiotic Akkermansia.

[Changes of microcirculation in superficial tissues of acupoint regions of lower leg during menstrual cycle in healthy young girls].

OBJECTIVE: To observe changes of microcirculation in the superficial regions of acupoints of the three Yin meridians of foot during the menstrual cycle in young college students, so as to provide experimental evidence for explaining the saying of traditional Chinese medicine that acupoints reflect the state of physiological and pathological activities of the internal organs. METHODS: Ninety healthy female volunteer college students were recruited in the present study. The subjects were asked to take a supine position on an examination couch to expose the Yuan-primary acupoints Taixi (KI3), Taibai (SP3) and Taichong (LR3), and Xi-cleft acupoints Shuiquan (KI5), Diji (SP8) and Zhongdu (LR6) which are related to the uterus of the three Yin meridians of foot， the crossing acupoints of the three Yin meridians of foot Sanyinjiao (SP6), non-specific acupoint of the Spleen meridian Xuehai (SP10), non-related meridian acupoint Xuanzhong (GB39) and non-meridian-non-acupoint (being at the same level of GB39, between the Stomach and Gallbladder meridians on the lateral aspect of the lower leg). The laser speckle blood flow imaging technique was used to detect the state of microcirculation (average blood perfusion volume) during menstrual, follicular, ovulatory and luteal phases. RESULTS: The average blood perfusion volume (ABPV) of the right SP8 region was significantly lower in the menstrual phase than in the ovulation and luteal phases (P<0.05), and in the follicular phase than in the ovulation phase (P<0.05). In the left LR6 region, the ABPV was obviously lower in the menstrual period than in the follicular, ovulation and luteal phases (P<0.05). In the SP8, SP6, KI3 and KI5 regions, the ABPV was significantly higher in each of the 4 phases on the left side than on the right side (P<0.05). In the right GB39, the ABPV in each of the 4 phases was apparently higher on the right side than on the left side (P<0.05). In the SP10 region, the ABPV was considerably higher on the left side than on the right side in the ovulation period (P<0.05). The ABPV of SP3 in the menstrual phase and that of the non-acupoint in the luteal phase were significantly higher on the right side than on the left side (P<0.05). CONCLUSION: The blood perfusion of microcirculation in the superficial tissues of Xi-cleft acupoints SP8 and LR6 is obviously lower in the menstrual phase than in both of the ovulation and luteal phases in healthy young college students, which may specifically reflect the periodical activities of the uterus in the physiological state, and provide a basis of acupoint selection for menstrual healthy care.

Exploration on the feasibility of moxibustion in prevention and treatment of COVID-19 from the perspective of modern medical mechanism.

Novel coronavirus pneumonia (COVID-19) is rampant in many countries and regions and there is no time to delay the exploration of the scheme for its prevention and control. The pathogenic characteristics of novel coronavirus and the effect of moxibustion for warming up yang and strengthening the antipathogenic qi were analyzed in this paper. From the perspective of modern medical mechanism, during the prevention and treatment of novel coronaviral infection, moxibustion may be able to prevent and treat COVID-19 by improving the body's immunity so as to conquer virus, by anti-inflammation to alleviate the inflammatory response of COVID-19 and by improving lung function to inhibit pulmonary fibrosis.

[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.

[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.

[Progress of researches on electrical characteristics of meridians and acupoints in recent 10 years].

The electrical characteristics of meridians and acupoints have been being one of the hot topics discussed by scholars, because of many influencing factors and inconsistent research results. In the present article, we collected papers published in Chinese or English in recent 10 years from PubMed, CNKI, and VIP databases by using key words of"acupuncture""meridian""resistance""capacitance""electrodermal"and"impedance". Then, we make an analysis about its development from three aspects, 1) manifestations of electrical properties of acupoints (low dermal resistance under pathological state, imbalance between left and right sides of the synonym acupoints), 2) clinical application of acupoint electrical characteristics for diagnosis of clinical disorders and evaluation of therapeutic effect, and 3) current situations of development of meridian detection instruments based on electrical characteristics (improving stability of instruments，expansion of the detected regions and measuring time, realization of visualization, and operational automation). In the process of coming studies, we highly recommend that more attention should be paid to the acupoints' "dynamic changes"， and forming a standardized research plan, strengthening domestic and international academic exchanges and cooperation are definitely necessary in order to validate the objectivity and specificity of electrical characteristics of meridians and acupoints, further expanding its clinical application.

[Regularity of body surface resistance at the acupoints of three yin meridians of the foot in reflecting physiological changes of the uterus].

OBJECTIVE: To investigate the specific regularity of body surface resistance at different acupoints of the meridians associated with the uterus in reflecting menstrual cycle by observing the change in body surface resistance at source points, cleft points, confluent points, and non-specific points of three yin meridians of the foot in different menstrual cycles in normal female college students, to lay a foundation for the in-depth research on the mechanism of acupoints reflecting the function of zang-fu, and to provide a reference for the clinical and scientific research on the biophysical characteristics of menstrual cycle-related acupoints in normal female. METHODS: A total of 90 normal female college students were recruited. The source points, cleftpoints, confluent points, and non-specific points of three yin meridians of the foot which were located in the adjacent spinal segments of the uterus were selected, and body surface resistance was monitored for 30 consecutive minutes at the same time-points of menstrual phase, follicular phase, ovulation phase, and luteal phase to observe the change in the resistance of each acupoint during the menstrual cycle. RESULTS: There was no significant change in the resistance value of unilateral acupoints during the menstrual cycle (P>0.05). In the same period, there was no significant difference in resistance value between unilateral three source points, three cleftpoints, different acupoints of the spleen meridian, and different acupoints of lumbar 4 dermatomere (P>0.05). As for the comparison of resistance of the same acupoint at the left and right sides, Taichong (LR3) at the left side had a higher resistance value than that at the right side in the menstrual phase (P<0.05); Taibai (SP3) at the left side had a higher resistance value than that at the right side in the ovulation phase (P<0.05); Zhongdu (LR6) at the left side had a higher resistance value than that at the right side in the follicular phase, the ovulation phase, and the luteal phase (P<0.05); Taixi (KI3), Diji (SP8), and Sanyinjiao (SP6) at the left side had a higher resistance value than those at the right side in the menstrual phase, the follicular phase, the ovulation phase, and the luteal phase (P<0.05); Shuiquan (KI5) at the left side had a lower resistance value than that at the right side in these four phases (P<0.05). CONCLUSION: The change trend of the resistance of the acupoints at the left and right sides associated with the three yin meridians of the foot can specifically reflect the change in qi and blood in the uterus during the menstrual cycle. The change trend of the source and cleft points of the liver meridian in the menstrual phase is different from that in the other phases, and the change trend of SP3, a source point of the spleen meridian, in the ovulation phase is different from that in the other phases, which suggests the specificity of meridian points in reflecting function. The mechanism by which meridian points reflect the function of zang-fu is associated with the meridian points and the spinal cord segments of zang-fu, and meanwhile, it has a specific relationship with the meridians to which meridian points belong and the attributes of acupoints.

[Application characteristics of abdominal acupuncture based on data mining technique].

OBJECTIVE: To investigate the disease spectrum and predominant diseases treated by abdominal acupuncture by data mining and analysis of journal articles on abdominal acupuncture, and to provide a reference for clinical diagnosis and treatment. METHODS: Based on the database of abdominal acupuncture established by the research group, the data mining technique was used for the analysis and extraction of the articles on abdominal acupuncture included in this study. RESULTS: A total of 788 original journal articles were included. Six departments and 96 disease categories, among which there were 45 internal diseases (46.84%) and 18 surgical diseases (18.75%) were involved. As for the diseases involved, cervical spondylosis had the highest frequency of 84, followed by low back and leg pain with a frequency of 77 and stroke sequela with a frequency of 67. Of all 788 studies, 519 (65.86%) used abdominal acupuncture combined with other therapies with a total frequency of 552, among which acupuncture had the highest frequency of 135 (24.46%), followed by oral administration of traditional Chinese medicine with a frequency of 81 (14.67%) and moxibustion with a frequency of 80 (14.49%). Abdominal acupuncture had a marked clinical effect in the treatment of various diseases, with the highest effective rate of 95.10% in surgical diseases. CONCLUSION: Abdominal acupuncture has a wide disease spectrum and is most frequently used for the treatment of cervical spondylosis, with a marked clinical effect. Abdominal acupuncture has unique therapeutic characteristics and advantages, but it can achieve a better clinical effect when combined with other therapies.

[Effect of Manual Acupuncture, Electroacupuncture and Moxibustion on Intestinal Motility and Expression of Enteric Nervous Activity Related Proteins in Functional Constipation Rats].

OBJECTIVE: To compare the effect of manual acupuncture (MA), electroacupuncture (EA) and moxibustion interventions on intestinal motility and expression of enteric nervous activity related proteins calcitonin gene related peptide (CGRP), transient receptor potential vanilloid 1 (TRPV 1) and proteinase activated receptor-4 (PAR-4) in colon tissue of rats with functional constipation (FC), so as to select a better intervention method for FC. METHODS: Sixty male SD rats were randomly divided into blank control (n=8), model (n=11), medication (n=8), MA (n=11), EA (n=11), and moxibustion (n=11) groups. The FC model was established by gavage of suspension of loperamide hydrochlorid for 6 days. Rats of the medication group were treated by gavage of cisapride (3 mg/kg), once daily for 6 days. MA, EA or moxibustion was separately applied to bilateral "Tianshu"(ST 25) and "Shangjuxu"(ST 37) for 15 min, once daily for 6 days. The stool weight within 24 h was measured every day, and the intestinal propulsive rate was calculated by feeding the rats with suspension fluid containing sodium carboxymethylcellulose and active carbon powder (3%) on the last day of the experiment. The expression levels of CGRP, TRPV 1 and PAR-4 proteins and genes in the colon tissue were measured by Western blot and quantitative real-time PCR, respectively. RESULTS: Compared with the control group, the stool weight within 24 h and intestinal propulsive rate were significantly decreased in the model group (P<0.01). Compared with the model group, the two indexes considerably increased in the medication, MA and EA groups (P<0.05, P<0.01), and the intestinal propulsive rate was also notably increased in the moxibustion group (P<0.05), suggesting an improvement of the intestinal motility after the treatment. The expression levels of intestinal CGRP, TRPV 1 and PAR-4 proteins and genes were significantly higher in the model group than in the control group (P<0.01), and considerably lower in the medication, MA, EA and moxibustion groups than in the model group (P<0.05, P<0.01, except the protein expression of CGRP in the moxibustion group). No significant differences were found among the medication, MA, EA and moxibustion groups in the stool weight, between the medication and EA groups and between the EA and moxibustion groups in the intestinal propulsive rate, and among medication, EA and moxibustion groups in the expression levels of TRPV 1 mRNA, and among the medication, MA and EA groups in the expression levels of CGRP, TRPV 1 and PAR-4 proteins (P<0.05). CONCLUSIONS: MA, EA and moxibustion interventions can promote the intestinal motility in FC rats, which may be related to their functions in down-regulating the expression of CGRP, TRPV 1 and PAR-4 proteins and genes (except CGRP in the moxibustion group).

[Effects of Different Acupuncture and Moxibustion Methods on Plasma NO, NOS and VIP Contents and the Expression of Colonic VIP Protein in Functional Constipation Rats].

OBJECTIVE: To compare the effects of filiform needling, electroacupuncture, and moxibustion on functional constipation in rats, and to explore the possible mechanism of these three different methods. METHODS: Male SD rats were randomly divided into blank control group (n=8), model group (n=11), medication group (n=8), filiform needling group (n=11), electroacupuncture group (n=11), and moxibustion group (n=11). Functional constipation model was established by intragastric administration with the suspension of loperamide hydrochloride, daily for six days in a week. One hour after each gavage, the medication group was treated with cisapride suspension, while the other three groups were treated with filiform needling, electroacupuncture, and moxibustion, respectively, at "Tianshu"(ST 25), "Shangjuxu" (ST 37) acupoints. The first defecation time was recorded. NO, NOS and VIP (vasoactive intestinal peptide) levels in plasma were detected by ELISA. Immuohistochemical and Western blot methods were applied to test VIP expression in the colonic tissue. RESULTS: Compared with the blank control group, the first defecation time was prolonged, and the NO, NOS and VIP contents in plasma were increased in the model group (P<0.05, P<0.01), accompanied with increased score of VIP in the smooth muscle of colonic wall(P<0.05)and elevated VIP expression in colonic tissue(P<0.01). Compared with the model group, the first defecation time was shortened in the medication, filiform needling, electroacupuncture, and moxibustion groups(P<0.05), while decreased NO, NOS and VIP contents in plasma (P<0.01,P<0.05), decreased score of VIP in the smooth muscle of colonic wall(P<0.05), and lower expression level of VIP in colonic tissue(P<0.01)were observed in the four treatment groups. In contrast, the plasma VIP content in the electroacupuncture group was lower than that in the medication group (P<0.01), while colonic VIP expression decreased in the moxibustion group(P<0.01). The NO, NOS and VIP contents in plasma and score of VIP in the smooth muscle of colonic wall in the electroacupuncture group were lower than those in the filiform needling group and the moxibustion group(P<0.01, P<0.05), but the colonic VIP expression in the moxibustion group was lower than that in the filiform needling group(P<0.05)and electroacupuncture group(P<0.01). CONCLUSIONS: All the three different kinds of acupuncture and moxibustion methods have positively regulatory effect on functional constipation; electroacupuncture is the best for the regulation of plasma NO, NOS and VIP contents, while moxibustion is the best for the regulation of VIP expression in colonic tissue.

[Thinking on designation of sham acupuncture in clinical research].

Randomized controlled trials (RCT) is the source of the raw data of evidence-based medicine. Blind method is adopted in most of the high-quality RCT. Sham acupuncture is the main form of blinded in acupuncture clinical trial. In order to improve the quality of acupuncture clinical trail, based on the necessity of sham acupuncture in clinical research, the current situation as well as the existing problems of sham acupuncture, suggestions were put forward from the aspects of new way and new designation method which can be adopted as reference, and factors which have to be considered during the process of implementing. Various subjective and objective factors involving in the process of trial should be considered, and used of the current international standards, try to be quantification, and carry out strict quality monitoring.

[Current situation of the standardization of acupuncture and moxibustion in Taiwan].

The current situation of the standardization of acupuncture and moxibustion in the Taiwan region is introduced in this paper from the three aspects, named the development state of standard of acupuncture and moxibustion in Taiwan, the implementation of Taiwan district standard and the standardization of acupuncture and moxibustion in Taiwan. At present, the relevant standards of acupuncture and moxibustion in Taiwan just include the standard operation procedure of acupuncture and moxibustion, the reference guideline of the safe operation in the medical service centers of traditional Chinese medicine, and the faculty standard of Chinese medicine hospital, etc. It is concluded that the current situation of the standardization of acupuncture and moxibusiton presented the weak awareness of the standardization of acupuncture and moxibustion in the industry, insufficient enterprise standard, less-quantity of the implemented standards and narrow coverage.