Genome-wide identification of GSK gene family in Senna tora L. and expression analyses / 药学学报

Glycogen synthase kinase 3/SHAGGY-like kinase (GSK3) proteins play important roles in regulating plant growth, development, and stress response. In order to reveal the characteristics of GSK family members in the medicinal plant Senna tora L., in this study, we conducted the identification and expression analyses of GSKs in S. tora based on its whole genome data, combined with bioinformatics and gene expression research methods. The results showed that a total of nine S. tora GSK genes were identified, all of which contained the GSK characteristic kinase domains. All members were distributed on six chromosomes, the encoding amino acid length ranged from 465 to 943 aa, the protein molecular weight was from 33.57 to 88.83 kDa, and the average isoelectric point was 8.2. The StoSKs were divided into four evolutionary branches, and the StoSKs in the same evolutionary branch shared the same exon/intron structure and conserved motifs. The expansion of the StoSKs gene family was mainly due to segment duplication events, and there were 17, 11, 8 and 7 pairs of collinear genes with Glycine max, Medicago truncatula, Arabidopsis thaliana and Oryza sativa, respectively. The promoter regions of StoSKs mostly contained responses elements related to stress stimulation, growth and development, and hormone induction. Transcriptome data analysis showed that StoSKs were expressed in different tissues, with the highest expression level in roots. Quantitative real-time PCR (qRT-PCR) analysis indicated that StoSKs in different evolutionary branches displayed a synergistic expression pattern response to light, and most of StoSKs could rapidly respond to NaCl stress with significantly up-regulated expression. All the results provide a basis for further analysis of the biological functions of the GSKs gene family in S. tora.

Safety of chronic high-dose calcium channel blockers exposure in children with pulmonary arterial hypertension.

Background: Chronic calcium channel blockers (CCBs) are indicated in children with idiopathic/heritable pulmonary arterial hypertension (IPAH/HPAH) and positive response to acute vasodilator challenge. However, minimal safety data are available on the long-term high-dose exposure to CCBs in this population. Methods: Patients aged 3 months to 18 years who were diagnosed with IPAH/HPAH and treated with CCB in the past 15 years were retrospectively reviewed. The maximum tolerated dose and the long-term safety of high-dose CCBs on the cardiovascular and noncardiovascular systems were assessed. Results: Thirty-two eligible children were enrolled in the study, with a median age of 9 (6-11) years old. Thirty-one patients were treated with diltiazem after diagnosis. The median maximum tolerated dose was 12.9 (9.8-16.8) mg/kg/day. Children younger than 7 years used higher doses than children in the older age group, 16.4 (10.5-28.5) mg/kg/day vs. 12.7 (6.6-14.4) mg/kg/day, P < 0.05. Patients were followed up for a median period of 6.2 (2.6-10.8) years. One patient died from a traffic accident, and others showed a stable or improved WHO functional class status. Thirteen (40.6%) and 10 (31.3%) patients developed arrhythmias and hypotension. Nine (28.1%) patients had sinus bradycardia, five (21.9%) had first-degree or second-degree type II atrial-ventricular blocks, and two (6.3%) had second-degree type II atrial-ventricular blocks. Most of these arrhythmias were transient and relieved after CCB dose adjustment. The most reported noncardiovascular adverse effect was gingival hyperplasia (13, 40.6%), accompanied by different degrees of dental dysplasia. No liver or kidney dysfunction was reported. Conclusion: Diltiazem was used in a very high dose for eligible children with IPAH/HPAH. The toxicity of long-term CCB use on the cardiovascular system is mild and controllable. Clinicians should also monitor the noncardiovascular adverse effects associated with drug therapy.

Improving the functionality of chitosan-based packaging films by crosslinking with nanoencapsulated clove essential oil.

The study aimed to obtain chitosan composite films with gratifying physical and functional properties. First, we developed a Pickering emulsion containing clove essential oil (CEO)-loaded nanoparticles with 1:2 (w/w) zein and sodium caseinate (NaCas). We found that in this ratio, the CEO-loaded zein-NaCas (C/ZN) nanoparticles had smaller particle size, proper polydispersity index (PDI) and zeta potential as well as higher encapsulation efficiency. Then, the acquired C/ZN nanoparticles were incorporated into chitosan film at three levels (0.2%, 0.4% and 0.6%), reducing the water vapor permeability to 4.62 × 10-6 g·s-1·m-1·Pa. Also, the tensile strength and break elongation of chitosan films were increased, reaching 38.67 MPa and 1.56%, respectively. The infrared spectroscopy verified that the intermolecular hydrogen bonds exist between chitosan and C/ZN nanoparticles. The chitosan composite films showed a controlled-release property of CEO in 96 h. Finally, the chitosan composite films showed the improved antibacterial property by creating larger inhibition zones against Escherichia coli (3.29 mm) and Staphylococcus aureus (6.15 mm). In general, we improved the water resistance, light blocking, mechanical strength, controlled-release and antibacterial properties of chitosan film with C/ZN nanoparticles. The current edible antibacterial films have great potential on applications for food preservation and food delivery system.

Effect of Modified Chaihu Shugansan on Gallbladder Function and Inflammatory Cytokines Levels in Treatment of Chronic Cholecystitis Cholelithiasis / 中国实验方剂学杂志

Objective:To observe the clinical efficacy and influence of modified Chaihu Shugansan combined with ursodeoxycholic acid tablets on inflammatory factors in treatment of chronic cholecystitis cholelithiasis （stagnation of liver and gallbladder Qi）. Method:One hundred and ten patients were randomly divided into control group （60 cases） and observation group （60 cases）. Both groups received lifestyle intervention， and oral ursodeoxycholic acid tablets， 50 mg/time， taken in the morning and evening meals. Patients in control group additionally took Yidanshu capsules orally， 4 capsules/time， 3 times/day. Patients in observation group additionally took modified Chaihu Shugansan orally， 1 dose/day. The treatment courses continued 3 months in both groups. Before and after treatment， traditional Chinese medicine （TCM） symptom scores were graded， the ultrasound status of chronic gallbladder inflammation， gallbladder contraction function and stones was graded， the levels of interleukin-6 （IL-6）， IL-8， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and nuclear transcription factor-<italic>κ</italic>B（NF-<italic>κ</italic>B）Were detected， and safety was evaluated. The efficacy for TCM syndromes， imaging efficacy and the efficacy for eliminating gallbladder stones were compared between the two groups. Result:The efficacy for TCM syndrome， efficacy on color ultrasound for chronic cholecystitis and the efficacy on imaging for cholelithiasis in the observation group were all better than those in the control group（<italic>Z</italic>=2.104<italic>，Z</italic>=2.076，<italic>Z</italic>=2.101，<italic>P</italic><0.05）. The thickness of gallbladder wall and volume of the gallbladder of the observation group were smaller than those of the control group （<italic>P</italic><0.01）， and gallbladder contraction function was higher than that in control group （<italic>P</italic><0.01）. Levels of IL-6， IL-8， TNF-<italic>α</italic> and NF-<italic>κ</italic>B in observation group were lower than those in control group （<italic>P</italic><0.01）. Conclusion:modified Chaihu Shugansan combined with ursodeoxycholic acid in the treatment of chronic cholecystitis and cholelithiasis （liver and gall Qi stagnation） is better than Yidanshu capsule combined with ursodeoxycholic acid sour scheme in terms of clinical efficacy， imaging efficacy， and elimination of gallbladder stones. It can reduce inflammation， and enhance gallbladder contraction， with high safety in clinical use.

Early therapeutic interventions of traditional Chinese medicine in COVID-19 patients: A retrospective cohort study / 中西医结合学报

OBJECTIVE@#To observe the early interventions of traditional Chinese Medicine (TCM) on the conversion time of nucleic acid in patients with coronavirus disease 2019 (COVID-19), and find possible underlying mechanisms of action.@*METHODS@#A retrospective cohort study was conducted on 300 confirmed COVID-19 patients who were treated with TCM, at a designated hospital in China. The patients were categorized into three groups: TCM1, TCM2 and TCM3, who respectively received TCM interventions within 7, 8-14, and greater than 15 days of hospitalization. Different indicators such as the conversion time of pharyngeal swab nucleic acid, the conversion time of fecal nucleic acid, length of hospital stay, and inflammatory markers (leukocyte count, and lymphocyte count and percentage) were analyzed to observe the impact of early TCM interventions on these groups.@*RESULTS@#The median conversion times of pharyngeal swab nucleic acid in the three groups were 5.5, 7 and 16 d (P < 0.001), with TCM1 and TCM2 being statistically different from TCM3 (P < 0.01). TCM1 (P < 0.05) and TCM3 (P < 0.01) were statistically different from TCM2. The median conversion times of fecal nucleic acid in the three groups were 7, 9 and 17 d (P < 0.001). Conversion times of fecal nucleic acid in TCM1 were statistically different from TCM3 and TCM2 (P < 0.01). The median lengths of hospital stay in the three groups were 13, 16 and 21 d (P < 0.001). TCM1 and TCM2 were statistically different from TCM3 (P < 0.01); TCM1 and TCM3 were statistically different from TCM2 (P < 0.01). Both leucocyte and lymphocyte counts increased gradually with an increase in the length of hospital stay in TCM1 group patients, with a statistically significant difference observed at each time point in the group (P < 0.001). Statistically significant differences in lymphocyte count and percentage in TCM2 (P < 0.001), and in leucocyte count (P = 0.043) and lymphocyte count (P = 0.038) in TCM3 were observed. The comparison among the three groups showed a statistically significant difference in lymphocyte percentage on the third day of admission (P = 0.044).@*CONCLUSION@#In this study, it was observed that in COVID-19 patients treated with a combination of Chinese and Western medicines, TCM intervention earlier in the hospital stay correlated with faster conversion time of pharyngeal swab and fecal nucleic acid, as well as shorter length of hospital stay, thus helping promote faster recovery of the patient. The underlying mechanism of action may be related to improving inflammation in patients with COVID-19.

The efficacy of acupuncture for the treatment and the fertility improvement in child-bearing period female with Hashimoto Disease: A randomized controlled study.

BACKGROUND: Hashimoto thyroiditis (HT) is highly prevalent among reproductive-aged women and has a substantial negative impact on fertility. Currently, there is no specific treatment for Hashimoto thyroiditis. We hypothesize that acupuncture can halt or delay the progression of HT and improve fertility in child-bearing period female. We therefore designed a randomized controlled trial to test this hypothesis by comparing the therapeutic effect of acupuncture vs sham acupuncture in patients with Hashimoto thyroiditis. METHODS: In this randomized controlled study, a total of 284 eligible patients will be assigned to acupuncture group (n = 142) or sham acupuncture group (n = 142) in a 1:1 ratio. All patients will receive 36 sessions in total for 12 consecutive weeks with the same acupoint prescription (RN23, ST9, RN17, RN4, RN6, ST36, SP6, KI6). The primary assessment is the titers of thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibody (TGAb). Secondary outcomes include the thyroid function, ovarian function, the rate of primary ovarian insufficiency, and pregnancy outcome. The thyroid function and thyroid antibodies tests will be measured at weeks 0, 4, 8, and 12 after randomization. The ovarian function will be examined on the 2nd to 4th day of the menstrual period in the 1st month, 2nd month and 3rd month compared with baseline. Both the pregnancy outcome and the rate of primary ovarian insufficiency will be evaluated 1 year after treatment. DISCUSSION: This will be the first large-scale trial specifically evaluating acupuncture therapy in child-bearing period female with Hashimoto thyroiditis. If the study confirms the effectiveness of acupuncture treatment, more consistent acupuncture therapy can be set up for clinical practice. TRIAL REGISTRATION: Chinese Clinical Trials Register identifier, ChiCTR2000031320, registered on 27 March 2020.

Recent progress in Helicobacter pylori treatment / 中华医学杂志(英文版)

The main challenge in the field of Helicobacter pylori (H. pylori) infection is antibiotic resistance, which influences the efficacy of eradication regimens. Bismuth-containing quadruple therapy has been confirmed as an effective regimen for eradicating H. pylori, especially in strains with antibiotic resistance. High-dose proton-pump inhibitor-amoxicillin dual therapy could decrease the use of unnecessary antibiotics, which is a promising alternative approach. Adjuvant therapy (specific probiotic or vitamin) also showed good results, although more evidence is needed. Novel anti-H. pylori drugs are needed, and the establishment of the H. pylori database is an effective way to acknowledge the real-time information of H. pylori management. This review provides the recent progress of H. pylori treatment, and further studies are needed to address the role of different regimens in improving H. pylori eradication rate, especially in strains with antibiotics resistance.

Extracts of Celastrus Orbiculatus Inhibit Cancer Metastasis by Down-regulating Epithelial-Mesenchymal Transition in Hypoxia-Induced Human Hepatocellular Carcinoma Cells / 中国结合医学杂志

OBJECTIVE@#To evaluate the effects of Celastrus Orbiculatus extracts (COE) on metastasis in hypoxia-induced hepatocellular carcinoma cells (HepG2) and to explore the underlying molecular mechanisms.@*METHODS@#The effect of COE (160, 200 and 240 µ g/mL) on cell viability, scratch-wound, invasion and migration were studied by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT), scratch-wound and transwell assays, respectively. CoCl was used to establish a hypoxia model in vitro. Effects of COE on the expressions of E-cadherin, vimentin and N-cadherin were investigated with Western blot and immunofluorescence analysis, respectively.@*RESULTS@#COE inhibited proliferation and metastasis of hypoxia-induced hepatocellular carcinoma cells in a dose-dependent manner (P<0.01). Furthermore, the expression of epithelial-mesenchymal transition (EMT) related markers were also remarkably suppressed in a dose-dependent manner (P<0.01). In addition, the upstream signaling pathways, including the hypoxia-inducible factor 1 α (Hif-1 α) and Twist1 were suppressed by COE. Additionally, the Hif-1 α inhibitor 3-5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), potently suppressed cell invasion and migration as well as expression of EMT in hypoxia-induced HepG2 cells. Similarly, the combined treatment with COE and YC-1 showed a synergistic effect (P<0.01) compared with the treatment with COE or YC-1 alone in hypoxia-induced HepG2 cells.@*CONCLUSIONS@#COE significantly inhibited the tumor metastasis and EMT by suppressing Hif-1 α/Twist1 signaling pathway in hypoxia-induced HepG2 cell. Thus, COE might have potential effect to inhibit the progression of HepG2 in the context of tumor hypoxia.

Correlation study between accumulation of triterpenoids and expression of relative genes in Alisma orientale / 中国中药杂志

To research the correlation between accumulation of triterpenoids and expression of key enzymes genes in triterpenoid biosynthesis of Alisma orientale,the study utilized UPLC-MS/MS method to detect eight triterpenoids content in the tuber of A. orientale from different growth stages,including alisol A,alisol A 24 acetate,alisol B,alisol B 23 acetate,alisol C 23 acetate,alisol F,alisol F 24 acetate and alisol G,and then the Real time quantitative PCR was used to analyze the expression of key enzymes genes HMGR and FPPS in triterpenoid biosynthesis. Correlation analysis showed that there was a significant positive relation between the total growth of these eight triterpenoids and the average relative expression of HMGR and FPPS(HMGR: r = 0. 998,P<0. 01; FPPS: r = 0. 957,P<0. 05),respectively. Therefore,the study preliminarily determined that HMGR and FPPS genes could regulate the biosynthesis of triterpenoids in A. orientale,which laid a foundation for further research on the biosynthesis and regulation mechanism of triterpenoids in A. orientale.

Comparison of Electroacupuncture and Mild-Warm Moxibustion on Brain-Gut Function in Patients with Constipation-Predominant Irritable Bowel Syndrome: A Randomized Controlled Trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To compare the effects of electroacupuncture (EA) and mild-warm moxibustion (Mox) therapies for constipation-predominant irritable bowel syndrome (C-IBS) patients.</p><p><b>METHODS</b>Sixty C-IBS patients were assigned to 2 groups by simple randomized method, i.e. EA group (30 cases) and Mox group (30 cases). Both EA and Mox treatments were performed on bilateral Tianshu (ST 25) and Shangjuxu (ST 37) for 30 min each time, 6 times per week, for 4 consecutive weeks. The gastrointestinal symptoms and psychological symptoms of the two groups were scored before and after treatment. The effects on the corresponding functional brain areas, namely the anterior cingulate cortex (ACC), insular cortex (IC) and prefrontal cortex (PFC) were observed by functional magnetic resonance imaging (fMRI) before and after treatment.</p><p><b>RESULTS</b>Compared with the Mox group, greater improvements in abdominal distension, defecation frequency, diffificulty in defecation and stool features were observed in the EA group (all P<0.01), both Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale scores were signifificantly decreased in the EA group (all P<0.01). Finally, decreased activated voxel values were observed in the ACC, right IC and PFC brain regions of EA group with 150 mL colorectal distension stimulation (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>Both EA and Mox could signifificantly improve some of the most intrusive symptoms of C-IBS patients, and EA was more effective than Mox. The therapeutic effect of these two therapies might through modulating of the brain-gut axis function. (Registration No. ChiCTRTRC-11001349).</p>

Research progress of pretreatment technology for mycotoxin detection in Chinese materia medica and complex matrices / 中国中药杂志

In the processes of planting, harvest, transport and storage, improper treatment of Chinese materia medica (CMM) and foodstuffs and agricultural products will result in fungal growth and mycotoxins contamination, which will not only directly affect the quality, safety and efficacy of these complex matrices, but also seriously threaten the consumers' health and lives. Therefore, the establishment of high-throughout analytical methods with high sensitivity for the determination of mycotoxins in CMM and foodstuffs and agricultural products at trace levels will provide reliable references for reducing the risk of mycotoxin exposure in humans. Due to the matrix complexity of CMM and foodstuffs and agricultural products, highly-effective pretreatment technologies are necessary for the establishment of such analytical techniques. In this review, the current extraction and purification methods commonly used for the detection of mycotoxins were summarized, the importance of pretreatment techniques for the precise quantification of mycotoxins in complex matrices such as Chinese herbal medicines was highlighted, as well as the development tendency about the pretreatment techniques for mycotoxins in complex matrices in the future was proposed.

Upregulated expression of Nucleostemin/GNL3 is associated with poor prognosis and Sorafenib Resistance in Hepatocellular Carcinoma.

Nucleostemin (NS)/GNL3 protein has been recently documented to be a nucleolar protein that was abundantly expressed in stem cells and cancer cells. Herein, we showed that NS was upregulated in HCC tissues and the expression of NS was inversely correlated with that of p53. Overexpression of NS predicted significantly worsened prognosis in HCC patients, suggesting that NS might serve as a prognostic marker of HCC. In addition, we found that depletion of NS sensitized HCC cells to sorafenib-induced apoptosis. Moreover, we found that the mechanism underlying NS-mediated sorafenib resistance involved dysregulated expression of p53, and downstream Bax and Bcl-2 proteins. NS interacted with p53 in HCC cells. Depletion of NS increased the expression of p53 and Bax, whereas impaired the level of cellular Bcl-2. Interference of NS enhanced the cytotoxic effects of sorafenib in HCC cells. Furthermore, ectopic expression of NS impaired the apoptosis of HCC cells following sorafenib exposure. Therefore, NS may contribute to sorafenib resistance in HCC cells through the modulation of p53 pathway and Bcl-2 proteins. These findings indicated that the combination of silencing NS expression and sorafenib treatment is a promising therapeutic strategy in treatment of HCC.

Effect of Chinese Herbal Medicine Jinlida Granule in Treatment of Patients with Impaired Glucose Tolerance / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diabetes mellitus (DM) remains a major health problem worldwide. Several clinical trials have shown the superiority of the Traditional Chinese Medicine in delaying or reversing the development and progression of DM. This study aimed to evaluate the efficacy of Jinlida (JLD) granule, a Chinese herbal recipe, in the treatment of impaired glucose tolerance (IGT) and its effect on the prevention of DM.</p><p><b>METHODS</b>Sixty-five IGT patients were randomized to receive one bag of JLD granules three times daily (JLD group, n = 34) or no drug intervention (control group, n = 31) for 12 weeks. Oral glucose tolerance test, glycated hemoglobin A1c (HbA1c), body mass index, blood lipids levels, fasting insulin, and insulin resistance calculated using homeostatic model assessment (HOMA-IR) of all the patients were observed and compared before and after the treatment.</p><p><b>RESULTS</b>Sixty-one participants completed the trial (32 in JLD group and 29 in the control group). There were statistically significant decreases in HbA1c (P < 0.001), 2-h plasma glucose (P < 0.001), and HOMA-IR (P = 0.029) in JLD group compared with the control group after 12 weeks of treatment. After 12 weeks of treatment, two (6.9%) patients returned to normal blood glucose, and five (17.2%) patients turned into DM in control group, while in the JLD group, 14 (43.8%) returned to normal blood glucose and 2 (6.2%) turned into DM. There was a significant difference in the number of subjects who had normal glucose at the end of the study between two groups (P = 0.001).</p><p><b>CONCLUSIONS</b>JLD granule effectively improved glucose control, increased the conversion of IGT to normal glucose, and improved the insulin resistance in patients with IGT. This Chinese herbal medicine may have a clinical value for IGT.</p>

Biological treatment for intervertebral disc degeneration / 中国骨伤

Neck shoulder pain or lumbocrural pain caused by intervertebral disc degeneration (IDD) could seriously affect the qualities life of patients. Current treatments mainly focus on alleviating pain and the symptoms of nerve compression, which could not radically stop the process of intervertebral disc degeneration, but conversely lead to high recurrence rate. In recent years, scholars have turned to study the biological treatment for repair and rebuild the intervertebral disc by biological molecular therapy, gene therapy, cell therapy and tissue engineering to solve the problem of intervertebral disc degeneration, while most of the above methods are still in animal experiments or in vitro experiments and the clinical application is still a long way to go.

[Clinical application of venous nutrition flap pedicled by medial plantar artery of the hallux on the medical aspect of the foot].

OBJECTIVE: To introduce the clinical application of venous nutrition flap pedicled by medial plantar artery of the hallux on the medical aspect of the foot. METHODS: Based on the anastomoses between the medial plantar artery of the hallux and the nutritional vein, the flap was designed with the perforator of medial plantar artery adjacent to the first metatarsal bone as the rotation point. The flap axis was along the vein at the medial aspect of the foot between rotation point and medial malleolus. RESULTS: 5 cases were treated with primary healing and complete survival flaps. The patients were followed up for 1-12 months with good match of texture and color. CONCLUSIONS: The venous nutrition flap pedicled by medial plantar artery of the hallux on the medical aspect of the foot can be transpositioned to repair the defect at forefoot.

Comparison of electroacupuncture and moxibustion on brain-gut function in patients with diarrhea-predominant irritable bowel syndrome: A randomized controlled trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To compare the effects of electroacupuncture (EA) and moxibustion therapies on patients with diarrhea-predominant irritable bowel syndrome (D-IBS).</p><p><b>METHODS</b>A total of 60 D-IBS patients were randomly allocated to the EA group (30 cases) and moxibustion group (30 cases). Before and after treatment, the gastrointestinal symptoms and psychological symptoms were scored by Visual Analogue Scale, Bristol Stool Form Scale, Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Rating Scale (HAMD); the expressions of 5-hydroxytryptamine (5-HT), 5-HT3 receptor (5-HT3R), and 5-HT4 receptor (5-HT4R) in the sigmoid mucosal tissue were measured by immunohistochemical staining. Additionally, the effects on the functional brain areas of the anterior cingulate cortex (ACC), insular cortex (IC) and prefrontal cortex (PFC) were observed by functional magnetic resonance imaging.</p><p><b>RESULTS</b>Compared with before treatment, both EA and moxibustion groups reported significant improvements in abdominal pain and abdominal bloating after treatment (P<0.01 or P<0.05). The moxibustion group reported greater improvements in defecation emergency, defecation frequency, and stool feature than the EA group (P<0.01). Both HAMA and HAMD scores were significantly decreased in the moxibustion group than in the EA group (P<0.01). Both groups demonstrated significantly reduced expressions of 5-HT, 5-HT3R and 5-HT4R in the colonic mucosa after treatment (P<0.01), with a greater reduction of 5-HT in the moxibustion group (P<0.05). Finally, decreased activated voxel values were observed in the left IC, right IC and PFC brain regions of patients in the moxibustion group under stimulation with 150 mL colorectal distension after treatment (P<0.05 or P<0.01), while in the EA group only PFC area demonstrated a reduction (P<0.05).</p><p><b>CONCLUSION</b>Moxibustion can significantly improve the symptoms of D-IBS, suggesting that moxibustion may be a more effective therapy than EA for D-IBS patients.</p>

Pharmacokinetics of loganin, ferulic acid and stilbene glucoside in Bushen Tongluo formula in vivo / 中国中药杂志

To study the pharmacokinetics characteristic of loganin, ferulic acid and stilbene glucoside in rat plasma after oral administration of Bushen Tongluo formula. The plasma samples were treated by using liquid-liquid extraction technique, the concentrations were determined by HPLC-UV. Johnson spherigel C18 column (4.6 mm x 250 mm, 5 μm) was adopted and eluted with the of mobile phase of methanol-water containing 0.01% glacial acetic acid in a gradient mode, with the flow rate at 1.0 mL x min(-1), column temperature at 30 degrees C and injection volume of 10 μL. According to the findings, loganin was determined at 235 nm, ferulic acid and stilbene glucoside were determined at 320 nm, with the sample size of 10 μL. The pharmacokinetic parameters of loganin, ferulic acid and stilbene glucoside were calculated by DAS 2. 0 software as follows: C(max) was (0.369 ± 0.042), (0.387 ± 0.071), (0.233 ± 0.044) mg x L(-1); t(max) was (0.226 ± 0.022), (0.282 ± 0.031), (0.233 ± 0.044) h; t(½β) was (6.89 ± 0.20), (10.73 ± 0.11), (6.93 ± 0.09) h; AUC(0-∞) was (1.91 ± 0.36), (3.22 ± 0.52), (1.52 ± 0.33) mg x h x L(-1); AUCO(0-t) was (1.62 ± 0.33), (2.58 ± 0.43), (1.30 ± 0.30) mg x h x L(-1); CL was (20.2 ± 4.0), (1.39 ± 0.23), (31.7 ± 6.9) L x h(-1) x kg(-1), respectively. The results showed that after the oral administration with Bushen Tongluo formula, loganin, ferulic acid and stilbene glucoside showed concentration-time curves in conformity with the two compartment model, with a rapid absorption, loganin and stilbene glucoside was excreted at a moderate speed, and ferulic acid was excreted slowly (but with the highest bioavailability). Bushen Tongluo formula can main maintain plasma concentration with three administrations everyday and so is suitable to be made into common oral preparation.

Effects of Zuogui pill, Yougui pill and relative compositions on differentiation towards germ cells of mouse embryonic stem cell 1B10 / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effects of Zuogui pill, Yougui pill and the relative compositions on the differentiation towards germ cells of stem cells.</p><p><b>METHOD</b>The rat drug sera for Zuogui pill, Yougui pill and the common composition of Zuogui pill and Yougui pill were prepared respectively as the experimental drugs; the mouse embryonic stem cell 1B10 (MESC-1B10) was used as the representative of stem cells; the above rat drug sera were used to intervene MESC-1B10 and the process was traced by microscopy imaging; after 72 h of the intervention, the RNAs were extracted from the different intervened MESC-1B10, cDNAs were synthesized immediately and finally the Real-time quantitative PCR (qPCR) was used to measure the expression patterns of the 10 reproductive-differentiation-related genes for each intervention.</p><p><b>RESULT</b>The rat drug serum of Zuogui pill (ZGW-RS) significantly up-regulated Oct-4 and SCP3 and significantly down-regulated GDF-9 and Stra8; the rat drug serum of Yougui pill (ZGW-RS) significantly up-regulated Oct-4, GDF-9, Mvh and SCP3 and significantly down-regulated Stra8, Itga6 and Itgb1; the rat drug sera for the common composition of Zuogui pill and Yougui pill (ZGWYGW-RS) significantly up-regulated Oct-4, SCP3 and ZP3 and significantly down-regulated GDF-9, Stra8, Itga6 and Itgb1.</p><p><b>CONCLUSION</b>ZGW-RS can initiate the change towards meiosis, but can not start the reproductive differentiation of MESC-1B10; YGW-RS can initiate the change towards meiosis, and can also start the reproductive differentiation of MESC-1B10 towards female germ cells; ZGWYGW-RS can initiate the change towards meiosis, and can lightly start the reproductive differentiation of MESC-1B10 towards female germ cells but the inductive effect is smaller than YGW-RS. The experimental results, on one hand, strengthen the knowledge about the influence of the relative compositions of Zuogui pill and Yougui pill on the reproductive differentiation of stem cells, on the other hand, help to explain the mechanism of the treatment of the infertility by Zuogui pill and Yougui pill.</p>

Dimethyl Cardamonin Exhibits Anti-inflammatory Effects via Interfering with the PI3K-PDK1-PKCalpha Signaling Pathway

Consumption of herbal tea [flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae)] is associated with health beneficial effects against multiple diseases including diabetes, asthma, and inflammatory bowel disease. Emerging evidences have reported that High mobility group box 1 (HMGB1) is considered as a key "late" proinflammatory factor by its unique secretion pattern in aforementioned diseases. Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone, DMC) is a major ingredient of C. operculatus flower buds. In this study, the anti-inflammatory effects of DMC and its underlying molecular mechanisms were investigated on lipopolysaccharide (LPS)-induced macrophages. DMC notably suppressed the mRNA expressions of TNF-alpha, IL-1beta, IL-6, and HMGB1, and also markedly decreased their productions in a time- and dose-dependent manner. Intriguingly, DMC could notably reduce LPS-stimulated HMGB1 secretion and its nucleo-cytoplasmic translocation. Furthermore, DMC dose-dependently inhibited the activation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), and protein kinase C alpha (PKCalpha). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-alpha, IL-1beta, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKCalpha signaling pathway.

Epigenetic modification of spinal miR-219 expression regulates chronic inflammation pain by targeting CaMKIIγ.

Emerging evidence has shown that miRNA-mediated gene expression modulation contributes to chronic pain, but its functional regulatory mechanism remains unknown. Here, we found that complete Freund's adjuvant (CFA)-induced chronic inflammation pain significantly reduced miRNA-219 (miR-219) expression in mice spinal neurons. Furthermore, the expression of spinal CaMKIIγ, an experimentally validated target of miR-219, was increased in CFA mice. Overexpression of spinal miR-219 prevented and reversed thermal hyperalgesia and mechanical allodynia and spinal neuronal sensitization induced by CFA. Concurrently, increased expression of spinal CaMKIIγ was reversed by miR-219 overexpression. Downregulation of spinal miR-219 in naive mice induced pain-responsive behaviors and increased p-NMDAR1 expression, which could be inhibited by knockdown of CaMKIIγ. Bisulfite sequencing showed that CFA induced the hypermethylation of CpG islands in the miR-219 promoter. Treatment with demethylation agent 5'-aza-2'-deoxycytidine markedly attenuated pain behavior and spinal neuronal sensitization, which was accompanied with the increase of spinal miR-219 and decrease of CaMKIIγ expression. Together, we conclude that methylation-mediated epigenetic modification of spinal miR-219 expression regulates chronic inflammatory pain by targeting CaMKIIγ.