Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: An exploratory randomized controlled trial.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an important occurrence in the natural history of idiopathic pulmonary fibrosis (IPF), associated with high hospitalization rates, high mortality and poor prognosis. At present, there is no effective treatment for AE-IPF. Chinese herbal medicine has some advantages in treating IPF, but its utility in AE-IPF is unclear. OBJECTIVE: The treatment of AE-IPF with Kangxian Huanji Granule (KXHJ), a compound Chinese herbal medicine, lacks an evidence-based justification. This study explores the efficacy and safety of KXHJ in patients with AE-IPF. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We designed a randomized, double-blind, placebo-controlled, exploratory clinical trial. A total of 80 participants diagnosed with AE-IPF were randomly assigned to receive KXHJ or a matching placebo; the treatment included a 10 g dose, administered twice daily for 4 weeks, in addition to conventional treatment. Participants were followed up for 12 weeks after the treatment. MAIN OUTCOME MEASURES: The primary endpoints were treatment failure rate and all-cause mortality. Secondary endpoints included the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, the modified British Medical Research Council (mMRC) score, and the St George's Respiratory Questionnaire for IPF (SGRQ-I) score. RESULTS: The rate of treatment failure at 4 weeks was lower in the intervention group compared to the control group (risk ratio [RR]: 0.22; 95% confidence interval [CI]: 0.051 to 0.965, P = 0.023). There was no significant difference in all-cause mortality at 16 weeks (RR: 0.75; 95% CI: 0.179 to 3.138; P > 0.999) or in the acute exacerbation rate during the 12-week follow-up period (RR: 0.69; 95% CI: 0.334 to 1.434; P = 0.317). The intervention group had a shorter length of hospitalization than the control group (mean difference [MD]: -3.30 days; 95% CI, -6.300 to -0.300; P = 0.032). Significant differences in the mean change from baseline in the mMRC (between-group difference: -0.67; 95% CI: -0.89 to -0.44; P < 0.001) and SGRQ-I score (between-group difference: -10.36; 95% CI: -16.483 to -4.228; P = 0.001) were observed after 4 weeks, and also in the mMRC (between-group difference: -0.67; 95% CI: -0.91 to -0.43; P < 0.001) and SGRQ-I (between-group difference: -10.28; 95% CI, -15.838 to -4.718; P < 0.001) at 16 weeks. The difference in the adverse events was not significant. CONCLUSION: KXHJ appears to be effective and safe for AE-IPF and can be considered a complementary treatment in patients with AE-IPF. As a preliminary exploratory study, our results provide a basis for further clinical research. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900026289). Please cite this article as: Li JS, Zhang HL, Guo W, Wang L, Zhang D, Zhao LM, Zhou M. Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: an exploratory randomized controlled trial. J Integr Med. 2023; 21(6): 543-549.

Electroacupuncture relieves chronic pain by promoting microglia M2 polarization in lumbar disc herniation rats.

Electroacupuncture has an effective analgesia on chronic pain caused by lumbar disc herniation (LDH) clinically, however, the underlying mechanism is unclear. In this study, we investigated whether electroacupuncture alleviated pain in LDH model rats by inducing spinal microglia M2 polarization. We established a noncompression LDH rat model by implanting autologous caudal nucleus pulposus into L5/L6 nerve root. Electroacupuncture (30 min/day) treatment on the ipsilateral side was started on the 8th postoperative day, once a day for consecutive 7 days. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were tested for pain behavior. Western blotting was used to detect the protein expression in lumbar enlargement (L5/L6). Immunofluorescence was used to detect iNOS+/Iba-1+ and Arg-1+/Iba-1+ and CB2R+/Iba-1+ in lumbar enlargement (L5/L6). We show that PWT and PWL decreased in the LDH group while Iba-1, iNOS, and TNF-α expression increased significantly in lumbar spinal dorsal horn (SDH) after LDH surgery, and revealing that microglia were activated and polarized towards proinflammatory M1 phenotype. Electroacupuncture treatment significantly increased PWT and PWL while reducing Iba-1, iNOS, and TNF-α expression, interestingly, Arg-1 and IL-10 expression were significantly increased. Moreover, electroacupuncture treatment led to CB2 receptors on microglia upregulation, while NF-κB and p-NF-κB expression in lumbar SDH downregulation. Our study indicated that electroacupuncture may reduce nociceptive hyperalgesia by inhibiting microglia activation and microglia M1 polarization and promoting microglia M2 polarization in lumbar SDH of LDH rats, which may be caused by the activation of CB2 receptors on microglia and inhibition of NF-κB pathway in lumbar SDH.

[Acupuncture and moxibustion in treatment of chronic obstructive pulmonary disease at stable stage: a network Meta-analysis].

The efficacy on chronic obstructive pulmonary disease (COPD) at stable stage treated with different methods of acupuncture and moxibustion was evaluated using network Meta-analysis method. The articles of the randomized controlled trial (RCT) on stable COPD treated with acupuncture and moxibustion were searched electronically in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Web of Science and Cochrane library. The search was conducted from the inception of the databases to March 20th, 2022. Data analysis was performed using R4.1.1, Stata16.0 and RevMan5.3 softwares. A total of 48 RCTs were included, involving 15 kinds of acupuncture and moxibustion interventions and a sample size of 3 900 cases. The results of network Meta-analysis showed that: ① For the forced expiratory volume in one second predicted (FEV1%), both the governor vessel moxibustion combined with conventional treatment (G+C therapy) and the yang-supplementing moxibustion combined with conventional treatment (Y+C therapy) obtained the better effect than that of the conventional treatment (P<0.05), and the G+C therapy was more effective compared with the thread-embedding therapy combined with conventional treatment (E+C therapy) and warm needling (P<0.05). ② Concerning to COPD assessment test (CAT) score, the results indicated that the Y+C therapy, and the mild moxibustion combined with conventional treatment (M+C therapy) were more effective when compared with the conventional treatment (P<0.05), and the effect of the Y+C therapy was better than that of the E+C therapy (P<0.05). ③ Regarding six-minute walking distance (6MWD), the effect of acupuncture combined with conventional treatment (A+C therapy) was better than that of either the E+C therapy or the conventional treatment (P<0.05). The effect of the G+C therapy was optimal for improving FEV1%, the Y+C therapy obtained the best effect for improving CAT score, and A+C therapy was the most effective for improving 6MWD. Due to the limitation of the quality and quantity of included studies, this conclusion needs to be further verified through high-quality RCT.

Folic acid relieves bone cancer pain by downregulating P2X2/3 receptors in rats.

BACKGROUND: Bone cancer pain (BCP) remains a clinical challenge due to the limited and side effects of therapeutic methods. Folic acid has been known as an FDA approved dietary supplement and proved to have an analgesic effect in neuropathic pain. Here we investigate the role and mechanism of folic acid in bone cancer pain of a rat model. METHODS: Walker 256 tumor cells were inoculated into the left tibia of rats to induce bone cancer pain model. Pain reflex were assessed by paw withdrawal threshold (PWT) response to Von Frey filaments and paw withdrawal latency (PWL) response to thermal stimulation. Folic acid was injected intraperitoneally to evaluate its analgesic effect in rats with bone cancer pain. Western blotting and qPCR were used to determine P2X2/3 receptor protein and mRNA levels in ipsilateral L4-6 dorsal root ganglion (DRG) and spinal dorsal horn (SDH). RESULTS: The PWT and PWL of rats with bone cancer pain were obviously decreased compared to the naïve and sham rats. Interestingly, continuous folic acid treatment significantly increased the PWT and PWL of rats with bone cancer pain. P2X2 and P2X3 receptors were clearly upregulated at both mRNA and protein expression in L4-6 DRG and SDH of rats with bone cancer pain. P2X2 and P2X3 receptors were mainly localized with CGRP (calcitonin gene-related peptide) or IB4 (isolectin B4) positive neurons in L4-6 DRG of rats with bone cancer pain. Notably, continuous folic acid treatment significantly reduced the expression of P2X2 and P2X3 receptors in L4-6 DRG and SDH of rats with bone cancer pain. Finally, intrathecal injection of A317491 (a selective antagonist of P2X2/3 receptors) markedly elevated the PWT and PWL of rats with bone cancer pain. CONCLUSION: These results suggest that folic acid has an effective antinociceptive effect on bone cancer pain, which is mediated by downregulating P2X2/3 receptors in L4-6 DRG and SDH of rats with bone cancer pain. Folic acid may be a novel therapeutic strategy in cancer patients for pain relief.

[Network Meta-analysis of heat-clearing and detoxifying Chinese medicine injections in treatment of acute exacerbation of chronic obstructive pulmonary disease].

This study aims to evaluate the efficacy and safety of heat-clearing and detoxifying Chinese medicine injections in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD). Randomized controlled trial(RCT) on the treatment of AECOPD with heat-clearing and detoxifying Chinese medicine injections were retrieved from 8 databases including CNKI and PubMed(from establishment to July 11, 2021). Related information in eligible articles was extracted, and the quality of the included articles was assessed by Cochrane collaboration's tool for assessing risk of bias. Stata SE 15.1 and ADDIS 1.16.6 were employed for data analysis. A total of 81 RCTs were screened out, involving 7 526 patients(3 782 in the experimental group and 3 744 in the control group). According to the statistical difference and network Meta-analysis, the injections are in the order of(1)Reduning Injection+conventional western medicine>Tanreqing Injection+conventional western medicine in improving the effective rate,(2)Reduning Injection+conventional western medicine>Tanreqing Injection+conventional western medicine in decreasing C-reactive protein(CRP),(3)Reduning Injection+conventional western medicine>Xiyanping Injection+conventional western medicine>Tanreqing Injection+conventional western medicine in reducing white blood cell count(WBC),(4)Yuxingcao Injection+conventional western medicine>Reduning Injection+conventional western medicine>Tanreqing Injection+conventional western medicine in lowering partial pressure of carbon dioxide(PaCO_2),(5)Yuxingcao Injection+conventional western medicine>Reduning Injection+conventional western medicine>Tanreqing Injection+conventional western medicine>Xiyanping Injection+conventional western medicine in improving partial pressure of oxygen(PaO_2), and(6)Qingkailing Injection+conventional western medicine>Tanreqing Injection+conventional western medicine in shortening mean hospital stay. In terms of safety, none of the five injections have serious adverse reactions. The five heat-clearing and detoxifying Chinese medicine injections are effective for AECOPD, but the mechanisms are different. Among them, Reduning Injection+conventional western medicine and Tanreqing Injection+conventional western medicine demonstrate better and more effects. Due to the differences in the quantity and quality of included studies, the conclusion needs to be further verified.

[Effects of root exudates C:N on soil physical and chemical characteristics and soil respiration in Robinia pseudoacacia plantation]. / æ ¹ç³»åˆ†æ³Œç‰©C∶N对刺槐林地土壤理化特征和土壤呼吸的影响.

We explored the effects of C:N ratio in root exudates of Robinia pseudoacacia plantations on soil nutrient cycling and microbial activity on the Loess Plateau. We collected in-situ soil from the R. pseudoacacia plantations with essentially identical habitat conditions and growing time of 15, 25, 35, and 45 years. By adding root exudates with different C:N ratios (N only, C:N=10, C:N=50, C:N=100, C only) to the soil and using deionized water as a control, we analyzed the effects of C:N ratio of root exudates on the physicochemical properties of elements such as carbon, nitrogen and phosphorus, soil pH, and soil respiration. The results showed that: 1) Organic carbon content was positively correlated with the C:N ratio of root exudates. Soil organic carbon (SOC) decomposition was faster when root exudates C:N=10. Higher C:N ratio of root exudates (C:N=100) could inhibit SOC decomposition, but only C addition had no significant effect on SOC. 2) Different root exudate C:N produced no significant influence on the total nitrogen. The addition of carbon promoted microbial uptake of ammonium nitrogen, while the addition of nitrogen promoted the nitrification of ammonium nitrogen. As the C:N ratio of root exudates increased, soil ammonium nitrogen content decreased. 3) The addition of nitrogen would reduce soil pH and increase soil total phosphorus content. 4) Soil respiration of R. pseudoacacia plantations was positively correlated with the C:N ratio of root exudates. With the increases of C:N ratio, the promoting effect of root exudates on soil respiration at 25 and 35 years R. pseudoacacia plantations was stronger. In conclusion, higher C:N ratio of root exudates will significantly promote the effect on soil respiration of R. pseudoacacia plantations. Our results improved the understan-ding of the root-soil-microbial interactions in forests.

New Frontier in Antiviral Drugs for Disorders of the Respiratory System.

BACKGROUND: COVID-19 is still soaring, and the new delta COVID-19 variant is on the rise and spreading around the world. OBJECTIVE: We conducted a patent analysis to better understand the therapeutic strategy developed for antivirals available for the disorders of the respiratory system. MATERIALS AND METHODS: European granted patents filed from January 2002 to June 2021 were analyzed. We used a combination of International patent classification (IPC) "A61p31/12" and "A61p11/00" to search the relevant documents. RESULTS: Our study showed R&D of antiviral drugs for disorders of the respiratory system to be decreasing over the past 20 years. Chemical drugs showed various chemical structures. The development of chemical drugs or herbal medicines appeared to commence earlier than the biological products. Also, the results indicated that large global companies play a leading role in developing kinase inhibitors as chemical drugs. CONCLUSION: There are three strategies for developing antiviral drugs for the disorders of the respiratory system, including chemical drugs, herbal medicines or natural products, and biological products. Herbal medicines may provide a new insight and approach to developing antiviral drugs for disorders of the respiratory system. A combination of chemical drugs and natural products may be a promising therapeutic method for treating patients with COVID- 19.

[Regularity of prescriptions for intermediate and advanced lung cancer based on latent structure combined with association rules].

The present study explored the regularity of prescriptions for the treatment of intermediate and advanced lung cancer to provide references for clinical medication. CNKI, Wanfang, VIP, and CBM were searched for the research papers on the treatment of lung cancer by Chinese medicine published from database inception to May 31, 2021. The relevant information of qualified papers was extracted to establish a database. The Chinese medicines with frequency >3% underwent analysis of the latent structure and association rules by Lantern 5.0 and SPSS Molder 14.1, respectively, and the prescription regularity in the treatment of intermediate and advanced lung cancer was analyzed based on the frequency description. A total of 713 papers were included, involving 327 Chinese medicines with a cumulative frequency of 12 794 and 106 prescriptions with a cumulative frequency of 824. The commonly used Chinese medicines were dominated by deficiency-tonifying, heat-clearing, phlegm-resolving, and cough/dyspnea-relieving drugs, such as Astragali Radix, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Ophiopogonis Radix, Poria, and Hedyotis Diffusa, which are cold, warm, and plain in nature and sweet, bitter, and pungent in flavor, and mainly act on lung, spleen, and stomach meridians. Commonly used prescriptions included Shashen Maidong Decoction, Liujunzi Decoction, and Baihe Gujin Decoction. The latent structure analysis revealed 32 latent variables and 65 hidden classes. Six comprehensive clustering models and 11 core prescriptions were obtained by professional knowledge inference. The common syndromes of intermediate and advanced lung cancer were inferred to be Qi and Yin deficiency in the lung, Qi deficiency in the lung and spleen, Yin deficiency in the liver and kidney, combined phlegm and stasis, phlegm-heat obstructing lung, and Qi stagnation and blood stasis. Forty-four strong associations were screened out by association rules analysis, including four pairwise strong associations(Polygonati Odorati Rhizoma→Ophiopogonis Radix, Polygonati Odorati Rhizoma→Glehniae Radix, Amomi Fructus→Atractylodis Macrocephalae Rhizoma, and Polygonati Rhizoma→Astragali Radix) and 40 triplet strong associations(such as Trichosanthis Radix+Glehniae Radix→Ophiopogonis Radix, Polygonati Odorati Rhizoma+Glehniae Radix→Ophiopogonis Radix, Trichosanthis Radix+Ophiopogonis Radix→Glehniae Radix, and Scutellariae Barbatae Herba+Codonopsis Radix→Hedyotis Diffusa). In the treatment of intermediate and advanced lung cancer, Qi-replenishing and Yin-nourishing drugs are mainly employed, assisted with cancer-resisting, toxin-removing, spleen-invigorating, phlegm/stasis-resolving, and blood-activating drugs based on syndrome differentiation. The roots were treated following the principles of tonifying lungs and replenishing the spleen, and symptoms following the principles of removing the toxin, dispelling stasis, and resolving phlegm.

[Study on the rule of acupoint selection in treatment of acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVE: To explore the characteristics and rule of clinical acupoint selection in treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: The clinical articles of acupuncture in treatment of AECOPD were retrieved from the databases of PubMed, EMbase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP and SinoMed, from the date of establishment to July 15, 2020. The articles were screened in accordance with the inclusion and exclusion criteria, the prescriptions of acupuncture and the relevant information of the acupoints and meridians were extracted to establish the database. The data mining methods i.e. Apriori association rule analysis and cluster analysis were used to analyse the using frequency, involving meridians, acupoint distributions, association rules and cluster of selected acupoints. RESULTS: A total of 54 articles were included, 67 acupuncture prescriptions were extracted, 69 acupoints were involved and the total using frequency was 475 times. The top 5 acupoints in frequency were Danzhong (CV 17), Feishu (BL 13), Zusanli (ST 36), Fenglong (ST 40) and Dingchuan (EX-B1). The main involved meridians were bladder meridian of foot-taiyang, conception vessel, stomach meridian of foot-yangming and lung meridian of hand-taiyin. The acupoints were mainly distributed in chest and abdomen, waist and dorsum. The mainly selected special points were five-shu points, front-mu points, convergent points and back-shu points. Twenty strong association rules were summarized by association rule analysis, including Fenglong (ST 40)Þ Zusanli (ST 36), Fengmen (BL 12)Þ Danzhong (CV 17), Tianshu (ST 25)Þ Zhongwan (CV 12), Dingchuan (EX-B1)+ Feishu (BL 13) Þ Danzhong (CV 17), Fenglong (ST 40)+ Feishu (BL 13) Þ Zusanli (ST 36), etc. Five cluster groups were summarized by cluster analysis, i.e. ①Feishu (BL 13), ② Dingchuan (EX-B1) and Danzhong (CV 17), ③ Chize (LU 5), Lieque (LU 7) and Fengmen (BL 12), ④Zusanli (ST 36) and Fenglong (ST 40), ⑤Tianshu (ST 25), Guanyuan (CV 4) and Zhongwan (CV 12). CONCLUSION: The local acupoints and acupoints along meridians are the main acupuncture prescriptions for AECOPD, and the special points are the predominated selection. The acupoint compatibility embodies the therapeutic principle of "strengthening vital qi to eliminate pathogenic factors and considering both the root cause and symptoms".

Camellia nitidissima Chi flower extract alleviates obesity and related complications and modulates gut microbiota composition in rats with high-fat-diet-induced obesity.

BACKGROUND: The aim of this study was to investigate the potential anti-obesity effects of Camellia nitidissima Chi flower extract (Cnfe) by examining its effects in terms of the regulation of lipid levels and modulation of gut microbiota in rats with high-fat-diet-induced obesity. RESULTS: Our results demonstrated that Cnfe significantly decreased weight gain by reducing appetite and decreasing high-fat food intake. Further, Cnfe restored normal lipid metabolism and improved insulin sensitivity and glucose tolerance in rats fed a high-fat diet. Real-time reverse transcription polymerase chain reaction and western blot results showed that Cnfe significantly decreased the expression of genes and proteins involved in adipogenesis and lipogenesis, and upregulated the expression of lipolysis genes. 16S ribosomal RNA sequencing of feces showed that Cnfe dramatically reversed dysbacteriosis in rats with high-fat-diet-induced obesity by decreasing the abundance of Firmicutes and increasing that of Bacteroidetes and Verrucomicrobia at the phylum level. CONCLUSION: The results demonstrate that Cnfe is a potential anti-obesity prebiotic nutrient that can prevent weight gain, ameliorate obesity-related dyslipidemia and hyperglycemia, inhibit liver fat accumulation, and modulate gut microbiota. © 2020 Society of Chemical Industry.

Effect of Comprehensive Therapy based on Chinese Medicine Patterns on Self-Efficacy and Effectiveness Satisfaction in Chronic Obstructive Pulmonary Disease Patients.

OBJECTIVE: To evaluate the effect of comprehensive therapy based on Chinese medicine (CM) patterns on self-efficacy and satisfaction with its effectiveness in patients with chronic obstructive pulmonary disease (COPD). METHODS: A total of 216 patients were randomly divided into the trial group (n =108) and the control group (n=108) based on the stratified and block randomization design. Patients in the trial group were treated with conventional Western medicine combined with Bufei Jianpi Granules (), Bufei Yishen Granules (), and Yiqi Zishen Granules () according to the CM patterns respectively, and patients in the control group were treated with conventional Western medicine. The COPD Self-Efficacy Scale (CSES) and the Effectiveness Satisfaction Questionnaire for COPD (ESQ-COPD) were employed in a 6-month treatment and in further 6 month follow-up visit. RESULTS: Among the 216 patients, 191 patients (97 in the trial group and 94 in the control group) fully completed the study. After 12-month treatment and follow-up, the mean scores of the trial group all continued to increase over time, which were significantly higher than those of the control group (P <0.05), and the improvement in the following trial group domain: negative affect domain (12.13%), intense emotional arousal domain (12.21%), physical exertion domain (11.72%), weather/environmental domain (13.77%), behavioral risk domain (7.67%) and total score (10.65%). The trial group also exhibited significantly higher mean scores in the ESQ-COPD (P <0.05) and the improvement in the following domain: capacity for life and work domain (30.59%), clinical symptoms domain (53.52%), effect of therapy domain (35.95%), convenience of therapy domain (35.54%), and whole effect domain (52.47%). CONCLUSIONS: Bufei Jianpi Granules, Bufei Yishen Granules and Yiqi Zishen Granules can improve the self-efficacy and satisfaction of COPD patients.

Three New Polyacetylene Glycosides from the Roots of Heracleum dissectum and Their Triglyceride Accumulating Activities in 3T3-L1 Cells.

Continually phytochemical study of the roots of Heracleum dissectum had led to the isolation of three previously undescribed polyacetylene glycosides (1-3), together with seven known compounds, including one polyacetylene (8) and six coumarins (4-7 and 9-10) using diverse chromatographic methods. The structures of these three new compounds were characterized and identified as deca-4,6-diyn-1-yl ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranoside (1), (8Z)-dec-8-ene-4,6-diyn-1-yl ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranoside (2), and (8E)-dec-8-ene-4,6-diyn-1-yl ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranoside (3) based on their physicochemical properties and extensive analyses of various spectroscopic data. Their triglycerides accumulating activities were assayed and the results showed that the three new polyacetylene glycosides (1-3) exhibited triglyceride accumulating activities in 3T3-L1 adipocytes.

A new cinnamic acid glycoside from roots of Heracleum dissectum.

From the roots of Heracleum dissectum Lebb., one new cinnamic acid glycoside derivative named dissectumoside (1), together with eight known compounds including three phenolics, three phenolic glycosides and two phenylpropanoic glycoside were isolated using various chromatographic methods. Among them compound 2-9 was isolated from the plant for the first time. Their structures were elucidated and identified on the basis of their physicochemical properties and by extensive analyses of NMR spectroscopy and high-resolution mass spectrometry. The results of triglyceride accumulation screening in 3T3-L1 cells showed that compounds 1, 5 and 9 exhibited significantly accelerating activities of adipogenesis in adipocytes.

An evaluation of activity tolerance, patient-reported outcomes and satisfaction with the effectiveness of pulmonary daoyin on patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Pulmonary Daoyin (PD) (evolved from ancient Chinese daoyin skills), is a rehabilitation technology that combines specially designed movements of the arms and body and controlled breathing exercises, to improve the physiological and psychological status of patients with chronic respiratory disease. Pulmonary rehabilitation is effective for patients with chronic obstructive pulmonary disease (COPD), and the efficacy of PD is unknown. The aim of this study is to investigate the effect of a PD program in enhancing activity tolerance, patient-reported outcomes and satisfaction with the effectiveness on patients with COPD. MATERIALS AND METHODS: The multi-center, randomized controlled trial was conducted from November 2011 to June 2012 in local communities in cities of the 11 research centers in China. It included COPD patients (moderate to very severe) who were recruited from an outpatient clinic. A randomized controlled study included 464 COPD patients who were randomly allocated either to the PD group, participating in a 3-month, ten times-weekly supervised PD-based pulmonary rehabilitation program, or to a control group continuing with regular medical treatment alone. Data were gathered using the 6-minute walking distance (6MWD) test, COPD patient-reported outcomes (COPD-PRO) and Effectiveness Satisfaction Questionnaire for COPD (ESQ-COPD), which was filled out at baseline and 3 months post-intervention. SAS 9.2 was used for statistical analysis. RESULTS: Of the 464 patients in the study, 461 were included in the full analysis set (FAS); 429 were in the per-protocol analysis set (PPS). After 3-month intervention, there was a significant difference between the two groups in 6MWD (FAS; P=0.049; PPS; P=0.041), total score and all domains of COPD-PRO (FAS; P=0.014; PPS; P=0.003) and ESQ-COPD (FAS; P=0.038; PPS; P<0.001). CONCLUSIONS: The PD program was able to improve the activity tolerance level and satisfaction of COPD patients because of its effectiveness.

A New Anti-Inflammatory Alkaloid from Roots of Heracleum dissectum.

Using various chromatographic methods, a new piperidinone alkaloid, (3S)-3-{4-[(1E)-3-hydroxyprop-1-en-1-yl]-2-methoxyphenoxy}piperidin-2-one (1), together with 10 known compounds, bergapten (2), xanthotoxol (3), isopimpinellin (4), isobergapten (5), heratomol-6-O-ß-d-glucopyranoside (6), scopoletin (7), apterin (8), 3-methoxy-4-ß-d-glucopyranosyloxypropiophenone, (praeroside; 9), tachioside (10) and coniferin (11), were isolated from roots of Heracleum dissectum Ledeb. Their structures were elucidated on the basis of physicochemical properties and the detailed interpretation of various spectroscopic data. All the isolated compounds were screened for anti-inflammatory activity in vitro. As the results, compound 1 and 8 showed significantly inhibitory activity on nitric oxide production in RAW264.7 cells.

Downregulation of miR-219 enhances brain-derived neurotrophic factor production in mouse dorsal root ganglia to mediate morphine analgesic tolerance by upregulating CaMKIIγ.

BACKGROUND: Increasing evidence suggests that microRNAs are functionally involved in the initiation and maintenance of pain hypersensitivity, including chronic morphine analgesic tolerance, through the posttranscriptional regulation of pain-related genes. We have previously demonstrated that miR-219 regulates inflammatory pain in the spinal cord by targeting calcium/calmodulin-dependent protein kinase II gamma (CaMKIIγ). However, whether miR-219 regulates CaMKIIγ expression in the dorsal root ganglia to mediate morphine tolerance remains unclear. RESULTS: MiR-219 expression was downregulated and CaMKIIγ expression was upregulated in mouse dorsal root ganglia following chronic morphine treatment. The changes in miR-219 and CaMKIIγ expression closely correlated with the development of morphine tolerance, which was measured using the reduction of percentage of maximum potential efficiency to thermal stimuli. Morphine tolerance was markedly delayed by upregulating miR-219 expression using miR-219 mimics or downregulating CaMKIIγ expression using CaMKIIγ small interfering RNA. The protein and mRNA expression of brain-derived neurotrophic factor were also induced in dorsal root ganglia by prolonged morphine exposure in a time-dependent manner, which were transcriptionally regulated by miR-219 and CaMKIIγ. Scavenging brain-derived neurotrophic factor via tyrosine receptor kinase B-Fc partially attenuated morphine tolerance. Moreover, functional inhibition of miR-219 via miR-219-sponge in naive mice elicited thermal hyperalgesia and spinal neuronal sensitization, which were both suppressed by CaMKIIγ small interfering RNA or tyrosine receptor kinase B-Fc. CONCLUSIONS: These results demonstrate that miR-219 contributes to the development of chronic tolerance to morphine analgesia in mouse dorsal root ganglia by targeting CaMKIIγ and enhancing CaMKIIγ-dependent brain-derived neurotrophic factor expression.

[Ethyl acetate-soluble chemical constituents from branch of Hypericum petiolulatum].

The stems and branches of Hypericum petiolulatum were extracted by alcohol and liquid-liquid extraction. Seven furofuran lignans were isolated from the ethyl acetate fraction of ethanol extract of H. petiolulatum by using silica gelchromatography, Sephadex LH-20 chromatography, medium-pressure liquid chromatography and preparative HPLC. Their structures were identified by the spectroscopic methods as pinoresinol (1), medioresinol (2), 8-acetoxypinoresinol (3), epipinoresinol (4), (+)-syringaresinol (5), (+)-1-hydroxysyringaresinol (6) and erythro-buddlenolE (7). All the isolates were firstly found in H. petiolulatum. In the bioassay, compound 7 showed remarkable antioxidative activity inhibiting Fe(+2)-cystine induced rat liver microsomal lipid peroxidation with inhibitory rate 38% at a concentration of 1 x 10(-6) mol · L(-1) (positive control Vit E with the inhibitory rate of 35% at the same concentration).

The effective evaluation on symptoms and quality of life of chronic obstructive pulmonary disease patients treated by comprehensive therapy based on traditional Chinese medicine patterns.

OBJECTIVE: To evaluate the efficacy of comprehensive interventions based on the three TCM patterns on symptoms and quality of life of COPD patients. DESIGN: An open-label, randomized, controlled trial. SETTING: Four hospitals in China. INTERVENTION: 352 patients were randomly divided into two groups. Patients in the trial group were given conventional Western medicine and Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules respectively; patients in the control group were given conventional Western medicine. Data collection was performed at baseline, in the 3rd and 6th month during the treatment period, and the 12th month during the follow-up period. OUTCOMES: Symptoms, including cough, sputum, pant, chest tightness, short of breath, lassitude, cyanosis and symptom total score; quality of life, measured by the WHOQOL-BREF questionnaire and adult COPD quality of life questionnaire (COPD-QOL). RESULTS: Of the 352 patients, 306 fully completed the study. After treatment and follow-up, there were significant differences between two groups in the following: cough, sputum, pant, chest tightness, shortness of breath, lassitude score and symptom total score (P<.05); physical, psychological, social and environment domain (P<.05) of the WHOQOL-BREF; daily living ability, social activity, depression symptoms and anxiety symptoms domain (P<.05) of the COPD-QOL. There were no differences between two groups in cyanosis and adverse events. CONCLUSION: Based on the TCM patterns, Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules have beneficial effects on symptoms and quality of life of COPD patients.

Ginsenoside Re reduces insulin resistance through activation of PPAR-γ pathway and inhibition of TNF-α production.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng is a well-known traditional Chinese medicine and has been used for treatment of various diseases for more than four thousand years in Asia. Ginseng saponins or ginsenosides, the active constituents are reported to possess antidiabetic activity, but their antihyperglycemic mechanisms are not fully elucidated. In the present study, the mechanisms of action of ginsenoside Re were investigated in vitro models. MATERIALS AND METHODS: 3T3-L1 cells were chosen as the model to investigate the molecular mechanisms of action of ginsenoside Re. Influence of ginsenoside Re on the adipogenesis was examined by determining TG levels in 3T3-L1 adipocytes by the method of TG oxidation enzyme. Glucose uptake in 3T3-L1 cells stimulated by insulin in the absence or presence of ginsenoside Re were quantified by measuring (3)H-2-deoxy-d-glucose levels. Cytokine proteins released into the medium including adiponectin and TNF-α were tested using respective ELISA kits. In addition, real time RT-PCR was conducted to investigate the expression changes of PPAR-γ and its responsive genes, ap2, adiponectin, IRS-1, GLUT4 and TNF-α. And western blot analysis was performed to determine the translocation of GLUT4. Finally, effects of ginsenoside Re on NO production in 3T3-L1 adipocytes and in macrophages were investigated through measurement of nitrite concentration by Griess reagent. RESULTS: Ginsenoside Re induced adipogenesis of 3T3-L1 adipocytes by accumulating TG, increased glucose uptake and up-regulated PPAR-γ2, IRS-1, ap2 and adiponectin genes expressions. Meanwhile, Re also increased production and release of adiponectin. Although having no effects on GLUT4 gene expression, Re facilitated GLUT4 protein translocation to the membranes. In addition, Re inhibited the expression and release of TNF-α. Finally, Re did not show inhibitory effects on NO production both in 3T3-L1 cells stimulated by LPS, TNF-α and IFN-γ and in LPS-stimulated mouse peritoneal macrophages. CONCLUSIONS: Ginsenoside Re exhibited the action of reducing insulin resistance through activation of PPAR-γ pathway by directly increasing the expressions of PPAR-γ2 and its responsive genes, adiponectin, IRS-1, ap2, inhibiting TNF-α production and facilitating the translocation of GLUT4 to promote glucose uptake and disposal in 3T3-L1 adipocytes.

Functional and psychosocial effects of pulmonary Daoyin on patients with COPD in China: study protocol of a multicenter randomized controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide. Pulmonary rehabilitation (PR) is an established intervention for the management of patients with COPD. Exercise training is an important part of PR, and its effectiveness in patients with COPD is well established. However, alternative methods of PR training such as Daoyin have not been appropriately studied. Hence, alternative forms of exercise training that require less exercise equipment and no specific training place should be evaluated. This paper describes the study protocol of a clinical trial that aims to determine if pulmonary Daoyin training will improve the exercise capacity and psychosocial function of patients with COPD in China. METHODS AND DESIGN: A multicenter, randomized, controlled trial will be conducted. A total of 464 patients meeting the inclusion criteria will be enrolled into this study with 232 patients in each of the trial group and the control group. Based on patient education, patients in the trial group will receive pulmonary Daoyin and continue with their usual therapy for three months. In the control group, patients will continue with their usual therapy. The primary outcome measures are exercise capacity assessed by the six-minute walking distance test and lung function. Secondary outcomes include dyspnea and quality of life. Measurements will be taken at baseline (month 0) and after the study period (month 3). DISCUSSION: It is hypothesized that pulmonary Daoyin will have beneficial effects in improving exercise capacity and psychosocial function of patients with stable COPD, and will provide an alternative form of exercise training that is accessible for the large number of people with COPD. TRIAL REGISTRATION: This trial has been registered in ClinicalTrials.gov. The identifier is NCT01482000.