Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling / 中国结合医学杂志

OBJECTIVE@#To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).@*METHODS@#According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy.@*RESULTS@#EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA.@*CONCLUSION@#EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.

Integrated strategy for biomarkers of stable coronary heart disease with phlegm and blood stasis syndrome based on RNA-seq and network pharmacology / 中国中药杂志

This study aimed to analyze the biological foundation and biomarkers of stable coronary heart disease(CHD) with phlegm and blood stasis(PBS) syndrome based on RNA-seq and network pharmacology. Peripheral blood nucleated cells from five CHD patients with PBS syndrome, five CHD patients with non-PBS syndrome, and five healthy adults were collected for RNA-seq. The specific targets of CHD with PBS syndrome were determined by differential gene expression analysis and Venn diagram analysis. The active ingredients of Danlou Tablets were screened out from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the "component-target" prediction was completed through PubChem and SwissTargetPrediction. The "drug-ingredient-target-signaling pathway" network of Danlou Tablets against CHD with PBS syndrome was optimized by Cytoscape software. After the target biomarkers were identified, 90 participants were enrolled for diagnostic tests, and 30 CHD patients with PBS syndrome were included in before-and-after experiment to determine the therapeutic effect of Danlou Tablets on those targets. As revealed by RNA-seq and Venn diagram analysis, 200 specific genes were identified for CHD with PBS syndrome. A total of 1 118 potential therapeutic targets of Danlou Tablets were predicted through network pharmacology. Through integrated analysis of the two gene sets, 13 key targets of Danlou Tablets in the treatment of CHD with PBS syndrome were screened out, including CSF1, AKR1C2, PDGFRB, ARG1, CNR2, ALOX15B, ALDH1A1, CTSL, PLA2G7, LAP3, AKR1C3, IGFBP3, and CA1. They were presumably the biomarkers of CHD with PBS syndrome. The ELISA test further showed that CSF1 was significantly up-regulated in the peripheral blood of CHD patients with PBS syndrome, and was significantly down-regulated after Danlou Tablets intervention. CSF1 may be a biomarker for CHD with PBS syndrome, and it is positively correlated with the severity of the disease. The diagnostic cut-off of CSF1 for CHD with PBS syndrome was 286 pg·mL~(-1).

Connotation and Clinical Application of Tong （Dredging） Method in Treatment of Coronary Heart Disease / 中国实验方剂学杂志

Tong （dredging） method in traditional Chinese medicine （TCM） emphasizes soothing the stagnated Qi， blood， and body fluid in zang-fu organs， meridians， and collaterals to remove pathogens， reinforce vital Qi， and balance Yin and Yang of the human body. Tong method can be adopted to disperse sweat pore， attack pathogenic Qi， harmonize Yin and Yang， as well as tonify deficiency， and resolve stagnation. It has been proved effective in treating coronary heart disease （CHD）， which falls into the category of "chest impediment and heart pain" in TCM， with the key pathogenesis lying in blood vessel obstruction. Therefore， dredging blood vessels is the primary therapeutic principle for CHD. Specifically， there are four aspects. The first is dispersing and dredging the sweat pore of the heart. If the sweat pore is occluded by pathogenic cold， which makes Yang-qi undissipated， Cinnamomi Ramulus， Piperis Longi Fructus， Alpiniae Officinarum Rhizoma， and Asari Radix et Rhizoma can be prescribed for warming and dredging heart Yang. If the Yang-qi of the heart and chest stagnated in the body， which hinders Qi and blood to nourish the myocardium， resulting in chest pain， Poria and Alismatis Rhizoma can be prescribed. For CHD due to atherosclerosis and inflammation， heat-clearing， toxin-removing， and inflammation-resisting Chinese medicinal herbs such as Coptidis Rhizoma and Rhei Radix et Rhizoma are recommended. The second is attacking and dredging the collaterals of the heart. Salviae Miltiorrhizae Radix et Rhizoma， Chuanxiong Rhizoma， Notoginseng Radix et Rhizoma， etc. can be prescribed for blood stasis， Trichosanthis Fructus， Allii Macrostemonis Bulbus， Pinelliae Rhizoma， etc. for phlegm， and Aquilariae Lignum Resinatum， Euodiae Fructus， etc. for pathogenic cold. Since the chronic disease can affect collaterals， Moschus and Santali Albi Lignum can be added to promote blood circulation and remove the obstruction of collaterals of the heart. The third is harmonizing and dredging the mind. Cinnamomi Ramulus， Coptidis Rhizoma， Cinnamomi Cortex， etc. are selected for restoring the coordination between the heart and the kidney. According to the specific syndrome， the methods of nourishing the mind and calming the nerves through tranquilizing the mind， calming down the mind， and inducing resuscitation can be selected using such Chinese medicines as Ziziphi Spinosae Semen， Polygalae Radix， and Draconis Ossa. The fourth is tonifying and dredging the Qi and blood of the heart. The deficiency syndrome of CHD is divided into Qi deficiency and kidney deficiency. Invigorating Qi and strengthening the heart are the first essentials for the treatment of CHD. In Qi invigoration， Qi and blood must be strengthened simultaneously to strengthen the heart and clear the pulse. Hence， Bazhentang modified by Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos can be chosen. In kidney Qi tonifying， kidney and heart must be strengthened simultaneously， and the methods of tonifying kidney and activating blood can be used. Ginseng Radix et Rhizoma and Astragali Radix are considered as the first choice for tonifying heart Qi， and Epimedii Folium and Morindae Officinalis Radix for tonifying kidney Qi， which are added with Salviae Miltiorrhizae Radix et Rhizoma and Rehmanniae Radix Praeparata to obtain the kidney-tonifying and blood-activating prescription. It is suitable for treating CHD due to kidney deficiency and blood stasis. Simultaneous treatment of heart and kidney is more suitable for middle-aged and elderly patients and chronically ill patients. Tong method can be used in various clinical diseases as well as CHD.

Effectiveness and safety of acupuncture for treating functional constipation: An overview of systematic reviews / 中西医结合学报

BACKGROUND@#Functional constipation (FC) is one of the most prevalent functional gastrointestinal disorders. Dissatisfaction with medications prescribed to treat FC may lead patients to seek alternative treatments. Numerous systematic reviews (SRs) examining the use of acupuncture to treat FC have reported inconsistent results, and the quality of these studies has not been fully evaluated.@*OBJECTIVE@#In this overview, we evaluated and summarized clinical evidence on the effectiveness and safety of acupuncture for treating FC and evaluated the quality and bias of the SRs we reviewed.@*SEARCH STRATEGY@#The search strategy was structured by medical subject headings and search terms such as "acupuncture therapy" and "functional constipation." Electronic searches were conducted in eight databases from their inception to September 2020.@*INCLUSION CRITERIA@#SRs that investigated the effectiveness and safety of acupuncture for managing FC were included.@*DATA EXTRACTION AND ANALYSIS@#Two authors independently extracted information and appraised the methodology, reporting accuracy, quality of evidence, and risk of bias using the following critical appraisal tools: (1) A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2); (2) Risk of Bias in Systematic Reviews (ROBIS); (3) Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A); and (4) the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). A κ index was used to score the level of agreement between the 2 reviewers.@*RESULTS@#Thirteen SRs that examined the clinical utility of acupuncture for treating FC were identified. Using the AMSTAR 2 tool, we rated 92.3% (12/13) of the SRs as "critically low" confidence and one study as "low" confidence. Using the ROBIS criteria, 38.5% (5/13) of the SRs were considered to have "low risk" of bias. Based on PRISMA-A, 76.9% (10/13) of the SRs had over 70% compliance with reporting standards. The inter-rater agreement was good for AMSTAR 2, ROBIS, and PRISMA-A. Using the GRADE tool, we classified 22.5% (9/40) of the measured outcomes as "moderate" quality, 57.5% (23/40) as "low" quality, and 20.0% (8/40) as "very low" quality. The inter-rater agreement was moderate when using GRADE. Descriptive analyses indicated that acupuncture was more efficacious than sham acupuncture for improving weekly complete spontaneous bowel movements (CSBMs) and for raising the Bristol Stool Form Scale (BSFS) score. Acupuncture appeared to be superior to anti-constipation drugs for improving weekly spontaneous bowel movements, the total effective rate, and the Patient Assessment of Constipation Quality of Life score. Although ten SRs mentioned the occurrence of adverse events, serious adverse events were not associated with acupuncture treatment.@*CONCLUSION@#Acupuncture may be more efficacious than sham acupuncture for improving CSBMs and BSFS scores and may be superior to anti-constipation drugs for improving bowel movement frequency, as well as quality of life. Limitations to current studies and inconsistent evidence suggest a need for more rigorous and methodologically sound SRs to draw definitive conclusions.@*SYSTEMATIC REVIEW REGISTRATION@#PROSPERO CRD42020189173.

Formulation of technical guidelines in line with characteristics and principles of traditional Chinese medicine changes to improve quality of such preparations--interpretation of Technical guidelines for the study of pharmaceutical changes in traditional Chinese medicines / 中国中药杂志

In leading the high-quality development of Chinese medicine preparations, it is an important link to formulate the scientific, reasonable, and feasible guidelines for the change of Chinese medicines in accordance with the change characteristics and principles of the Chinese medicines is an important work to promote the Technical guidelines for the study of pharmaceutical changes in traditional Chinese medicines was formed by a broad consensus based on the characteristics and research results of the pharmaceutical changes in Traditional Chinese Medicines(TCM)with the principles of science and risk management. This guideline has clarified the basic principles and requirements for the evaluation of changes in TCM, specified the research and verification work of common change scenarios, defined the boundaries of changes in TCM, and proposed to encourage the use of new technologies, new methods, and new excipients that meet product characteristics. It will definitely promote the quality improvement and the secondary development of TCM. In this article, the revision background and main content of the guideline were introduced, and the main features of the Guideline were analyzed, in order to provide references for the industry.

Cupping therapy for patients with chronic urticaria: A systematic review and meta-analysis / 中西医结合学报

BACKGROUND@#Chronic urticaria (CU) is a common skin disease, which has a negative effect on quality of life. Current treatments do not fully control the symptoms of urticaria for many CU patients, thus effective and safe treatments for CU are still needed.@*OBJECTIVE@#This review aims to evaluate the effectiveness and safety of cupping therapy in patients with CU.@*SEARCH STRATEGY@#The search strategy looked for the presence of related keywords, such as "chronic urticaria" and "cupping therapy," in the title and abstract of research articles indexed in major databases. Randomized controlled trials (RCTs) were selected after querying nine electronic databases from their inception to May 2019 with the above search terms.@*INCLUSION CRITERIA@#RCTs were included if they recruited patients with CU who were intervened with dry or wet cupping. Publications could be written in Chinese or English.@*DATA EXTRACTION AND ANALYSIS@#Data were extracted, and the studies were assessed for the quality of their methodological design and risk of bias. Meta-analyses of the RCT data were conducted to assess the total effective rate of the treatment as the primary outcome. Skin disease quality of life index score, recurrence rate, and adverse events were assessed as secondary outcomes. Subgroup analyses were conducted based on different interventions.@*RESULTS@#Thirteen comparisons from 12 RCTs involving 842 participants were included. There were no significant differences between wet cupping and medications in total effective rate (n = 372; risk ratio [RR] = 1.10, 95% confidence interval [CI] 0.97 to 1.25; P = 0.14) or recurrence rate (n = 240; RR = 0.56, 95% CI 0.23 to 1.36; P = 0.20). Cupping therapy, in combination with antihistamine treatment was more efficacious than antihistamines alone, with a greater total effective rate (n = 342; RR = 1.18, 95% CI 1.01 to 1.39; P = 0.03) and lower recurrence rate (n = 342; RR = 0.52, 95% CI 0.32 to 0.84; P = 0.007). Cupping therapy combined with acupuncture was more effective than acupuncture alone (n = 156; RR = 1.25, 95% CI 1.07 to 1.46; P = 0.006). No serious adverse events were reported.@*CONCLUSION@#Wet cupping may be as effective as treatment with antihistamines. When cupping therapy is used as an adjuvant therapy to antihistamines or acupuncture, it may enhance the efficacy. Results drawn from these studies should be interpreted with caution and applied with care to clinical practice, because of the poor quality among the studies that were reviewed.@*SYSTEMATIC REVIEW REGISTRATION@#PROSPERO, CRD42019137451.

Rules for acupoint selection in treatment of perimenopausal syndrome based on data mining technology / 中国针灸

<p><b>OBJECTIVE</b>To analyze the rules for acupoint selection of acupuncture and moxibustion in domestic clinical treatment of perimenopausal syndrome based on data mining technology in modern times.</p><p><b>METHODS</b>The relevant literature were retrieved from Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang database on this disease treated with clinical acupuncture and moxibustion in China from 1978 to 2013. The database of acupuncture-moxibustion prescription was set up. The relevant regulations of data mining technology were used to analyze the rules for acupoint selection.</p><p><b>RESULTS</b>Totally, 211 papers, 254 acupuncture-moxibustion prescriptions and 130 acupoints were included. The total frequency of acupoints application was 2193 times, with 14 meridians involved. The utilization of the acupoints in the lower limbs and on the back were 33.0% (723/2193) and 23.8% (521/2193) and those of yin and yang meridians were 51.8% (1136/2193) and 44.0% (965/2193), respectively. The utilization of the specific acupoints accounted for 88.7% (1946/2193).</p><p><b>CONCLUSION</b>In clinical treatment of perimenopausal syndrome with acupuncture and moxibustion in modern times, the acupoint selection from involved meridians is the basis, associated with multiple methods of acupoint combination; yin and yang meridians are equally important and the specific acupoints are considered particularly critical in application.</p>

Analysis on characteristics of meridians and acupoints of acupuncture and moxibustion for diarrhea in ancient based on data mining / 中国针灸

The data in literature of acupuncture and moxibustion on treatment of diarrhea from pre-Qin period to Qing dynasty was collected to establish prescription database and characteristics and rules of ancient acupuncture and moxibustion for diarrhea were analyzed with data mining technology. Totally 235 papers were collected and 76 acupoints were involved with 439 times of selection. The number and times of special acupoints were 72.37% (55/76) and 76.99% (338/439), respectively, which was more seen in front-mu acupoint and back-shu acupoint. The acupoints were distributed among 11 meridians. Moxibustion was applied in 53 papers while combination of acupuncture and moxibustion was used in 1 literature. As a result, acupuncture and moxibustion for diarrhea in ancient pay much attention on acupoint in back and abdomen, in which Tianshu (ST 25), Shen-que (CV 8), Guanyuan (CV 4) and Dachangshu (BL 25) were the most frequently used. The compatibility of front-mu acupoint and back-shu acupoint was very common. Selection of special acupoint was dominant. Besides crossing points that has the most intersection of meridian qi in the back and abdomen, acupoints below the elbow and knee joints, such as five-shu points, source point, luo-connecting point, eight confluence point and lower he-sea point were also taken into account. As for compatibility of special acupoints, the supportive degree between back-shu acupoint and confluence points or front-mu acupoint was the highest; the selections of meridians mainly were Bladder Meridian, Conception Vessel and Spleen Meridian; and application of moxibustion was highly valued. In conclusion, it is feasible to apply data mining technology to the clinical literature research of ancient acupuncture and moxibustion, which can provide evidence for summary of the traditional classical theory.

Quality improvement on acupuncture intervention report: application and perfection of STRICTA / 中国针灸

ABSTRACT Clinical application of standards for reporting interventions in clinical trials of acupuncture (STRICTA) is introduced in this article, and improving opinions are proposed as well. STRICTA has already been extensively applied in designation of acupuncture clinical trials, composition of articles and quality assessment of acupuncture literature. According to the present version of STRICTA, it is suggested that items such as "standards and methods on acupoint selection and location", "angle and direction of needle insertion" and "whether the subjects ever have been acupunctured" should be further perfected. Individuated treat protocols which is highlighted on treatment according to differentiation of syndromes according to different opportunities and stages of diseases should be promoted so as to give better expression to the characteristics of Chinese medicine and enhance the clinical value of the relative literature.

Thinking on the design scheme of clinical trial with the example of migraine treated by acupuncture / 中国针灸

Through the examples of explanatory and pragmatic trials on acupuncture for migraine and the comparison between research objectives, experiment environment and trial designs, the design of current clinical trial should focus on: (1) Making a point of continuum research on efficacy-effectiveness at trial design type; (2) Thinking highly of therapeutic effect criteria that could have a better show of trial purpose; (3) More use of qualitative research embedded in the randomized controlled trials. With these improvements, the effects of acupuncture could be evaluated more scientifically, objectively and comprehensively.

Biliary excretion of genistein and its metabolite at different doses in rats / 药学学报

<p><b>AIM</b>To study the biliary excretion of genistein and its metabolite at different doses in rats.</p><p><b>METHODS</b>Suspended in 0.5% CMC-Na solution, genistein was orally administered to rats at the dose of 6.25, 12.5 and 50 mg x kg(-1), separately. At various time intervals, the bile was collected. The bile was treated with beta-glucuronidase. The genistein in bile was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. Twenty microL solution was drawn and detected by high-performance liquid chromatography.</p><p><b>RESULTS</b>The accumulative biliary excretion of genistein was (42.56 +/- 6.54) , (75.17 +/- 18.87) and (126.60 +/- 34.78) microg at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. The total drug (genistein plus glucuronidated genistein) excreted from bile was (108.46 +/- 35.23), (423.46 +/- 158.31) and ( 853.74 +/- 320. 84) microg, and the ratio of glucuronidated genistein was 60.76% , 82.25% and 85.17% at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively.</p><p><b>CONCLUSION</b>The genistein was excreted mainly in the form of glucuronidated genistein in rat bile. The genistein and glucuronidated genistein were excreted in a nonlinear dose-dependent manner.</p>

Pharmacokinetics of m-nifedipine in Beagle dogs / 药学学报

<p><b>AIM</b>To study the pharmacokinetics of m-nifedipine (m-Nif) in Beagle dogs.</p><p><b>METHODS</b>The Beagle dogs were divided into two groups. m-Nif was intravenously administered to the Beagle dogs in group 1 at the dose of 0. 288 mg x kg(-1), and it was orally administered to the Beagle dogs in group 2, 3 and 4 at the dose of 1.152, 3.456 and 10.370 mg x kg(-1), respectively. m-Nif in plasma was detected by reversed phase high performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software.</p><p><b>RESULTS</b>When m-Nif was intravenously administered, the plasma concentration-time curve was fit to a two-compartment model and T1/2beta was 117 min. When m-Nif was orally administered, the plasma concentration-time curve was fit to a one-compartment model. T1/2 (Ke) and Cmax were 147 min and 20 microg x L(-1); at the low dose of 1.152 mg x kg(-1). T1/2 (Ke) was 122 min and Cmax was 36 microg x L(-1) at the middle dose of 3.456 mg x kg(-1). T1/2 (Ke) was 144 min and Cmax was 69 microg x L(-1) at the high dose of 10.37 mg x kg(-1), respectively.</p><p><b>CONCLUSION</b>It was showed that the speed of elimination of m-Nif was high in Beagle dogs. The absolute bioavailability of m-Nif given orally was very low.</p>

Effects of tanguticum maxim polysaccharide on ulcerative colitis induced by TNBS in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the effects of Tanguticum Maxim polysaccharide (TMP-1) on TNBS-induced colitis in rats.</p><p><b>METHOD</b>Rats with TNBS/ethanol-induced colitis were used and treated with TMP-1 and dexamethasone (DX). Seventy-two rats, including animals with TNBS-induced colitis, were treated with saline, TMP-1 (100, 200, 400 mg.kg-1) and DX. White blood cells were counted on the fifth day and the rats were killed by ether on the sixth day. SOD activity in serum, MPO and SOD activity of colonic tissue were measured.</p><p><b>RESULT</b>The remarkable effects of TMP-1 at dosage of 200, 400 mg.kg-1 on TNBS-induced colitis were observed. The ulcerative area was diminished and weight of colon was reduced. White blood cell population was reduced, SOD activity in serum and SOD activity of colon tissue were remarkably increased, and, MPO activity of colonic tissue was reduced.</p><p><b>CONCLUSION</b>TMP-1 has significant effects on TNBS-induced colitis in rats with lower side effects, which suggests the effective component of rhubarb on colitis perhaps is TMP. The mechanism of the actions of TMP may relate to its antiflammation, antioxidation and immunoloregulation.</p>