Effects of mind-body exercise on knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effect of mind-body exercise on improving knee osteoarthritis (KOA) and thereby informing osteoarthritis exercise rehabilitation. METHODS: The China National Knowledge Infrastructure (CNKI), Wanfang, PubMed/Medline, Cochrane Library, Web of Science, EBSCO, Embase, Scopus, and ProQuest databases were searched to identify randomized controlled trials (RCTs) that involved tai chi, yoga, and baduanjin interventions for KOA. The search period ranged from inception to October 25, 2022. The methodological quality of the included studies was evaluated by the Cochrane risk of bias assessment tool, and the included data were statistically analyzed and plotted using Review Manager 5.3 and Stata 14.0 software. RESULTS: We included 17 articles with a total of 1122 patients. Compared with the control group, mind-body exercise significantly improved patient pain (standardized mean difference (SMD) = -0.65, 95% confidence interval (CI) [-0.87, -0.42], p < 0.00001), stiffness (SMD = -0.75, 95% CI [-1.05, -0.45], p < 0.00001), physical function (SMD = -0.82, 95% CI [-1.03, -0.62], p < 0.00001), mental health (SMD = 0.31, 95% CI [0.11, 0.51], p = 0.002), and depression (SMD = -0.32, 95% CI [-0.50, -0.15], p = 0.0003). In terms of motor ability, mind-body exercise significantly increased the 6-min walking distance (SMD = 18.45, 95% CI [5.80, 31.10], p = 0.004) and decreased timed up and go test time (SMD = -1.15, 95% CI [-1.71, -0.59], p < 0.0001). CONCLUSIONS: The current study showed that mind-body exercise is safe and effective for KOA patients. However, given the methodological limitations of the included studies, additional high-quality evidence is needed to support the conclusions of this study.

Tanshinone IIA induces ER stress and JNK activation to inhibit tumor growth and enhance anti-PD-1 immunotherapy in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) remains at the forefront of new cancer cases, and there is an urgent need to find new treatments or improve the efficacy of existing therapies. In addition to the application in the field of cerebrovascular diseases, recent studies have revealed that tanshinone IIA (Tan IIA) has anticancer activity in a variety of cancers. PURPOSE: To investigate the potential anticancer mechanism of Tan IIA and its impact on immunotherapy in NSCLC. METHODS: Cytotoxicity and colony formation assays were used to detect the Tan IIA inhibitory effect on NSCLC cells. This research clarified the mechanisms of Tan IIA in anti-tumor and programmed death-ligand 1 (PD-L1) regulation by using flow cytometry, transient transfection, western blotting and immunohistochemistry (IHC) methods. Besides, IHC was also used to analyze the nuclear factor of activated T cells 1 (NFAT2) expression in NSCLC clinical samples. Two animal models including xenograft mouse model and Lewis lung cancer model were used for evaluating tumor suppressive efficacy of Tan IIA. We also tested the efficacy of Tan IIA combined with programmed cell death protein 1 (PD-1) inhibitors in Lewis lung cancer model. RESULTS: Tan IIA exhibited good NSCLC inhibitory effect which was accompanied by endoplasmic reticulum (ER) stress response and increasing Ca2+ levels. Moreover, Tan IIA could suppress the NFAT2/ Myc proto oncogene protein (c-Myc) signaling, and it also was able to control the Jun Proto-Oncogene(c-Jun)/PD-L1 axis in NSCLC cells through the c-Jun N-terminal kinase (JNK) pathway. High NFAT2 levels were potential factors for poor prognosis in NSCLC patients. Finally, animal experiments data showed a stronger immune activation phenotype, when we performed treatment of Tan IIA combined with PD-1 monoclonal antibody. CONCLUSION: The findings of our research suggested a novel mechanism for Tan IIA to inhibit NSCLC, which could exert anti-cancer effects through the JNK/NFAT2/c-Myc pathway. Furthermore, Tan IIA could regulate tumor PD-L1 levels and has the potential to improve the efficacy of PD-1 inhibitors.

Transport dynamics of watershed discharged diffuse phosphorus pollution load to the lake in middle of Yangtze River Basin.

Diffuse pollution, including that in the lower and middle reaches of the Yangtze River, is the primary source of pollution in several agricultural watersheds globally. As the largest river basin in China, the Yangtze River Basin has suffered from total phosphorus (TP) pollution in the past decade owing to diffuse pollution and aquatic ecology destruction, especially in the midstream tributaries and mid-lower reaches of the lakes. However, the transport dynamics of diffuse pollutants, such as phosphorus (P) from land to water bodies have not been well evaluated, which is of great significance for quantifying nutrient loss and its impact on water bodies. In this study, diffuse pollution estimation with remote sensing (DPeRS) model coupled with Soil and Water Assessment Tools (SWAT) was utilized to simulate the transport dynamics of P, investigate the spatial heterogeneity and P sources in the Poyang Lake Basin. Additionally, the P transport mechanism from land to water and the migration process in water bodies were considered to investigate the impact of each loss unit on the water body and evaluate the load generated by diverse pollution types. The estimated diffuse TP loss was 6016 t P·yr-1, and the load to inflow rivers and to Poyang Lake were 11,619 and 9812 t P·yr-1, respectively. Gan River Basin (51.09%) contributed most TP to Poyang Lake among five inflow rivers, while waterfront area demonstrated the highest TP load per unit area with 0.057 t km-2·yr-1. Our study also identified P sources in the sub-basins and emphasized agricultural diffuse sources, especially planting, as the most significant factor contributing to TP pollution. Additionally, to improve the aquatic environment and water ecological conditions, further nutrient management should be applied using a comprehensive approach that encompasses the entire process, from source transportation to the water body.

[A new xanthone from hulls of Garcinia mangostana and its cytotoxic activity].

Eight compounds were isolated from ethyl acetate fraction of 80% ethanol extract of the hulls of Garcinia mangostana by silica gel, Sephadex LH-20 column chromatography, as well as prep-HPLC methods. By HR-ESI-MS, MS, 1D and 2D NMR spectral analyses, the structures of the eight compounds were identified as 16-en mangostenone E(1), α-mangostin(2), 1,7-dihydroxy-2-(3-methy-lbut-2-enyl)-3-methoxyxanthone(3), cratoxyxanthone(4), 2,6-dimethoxy-para-benzoquinone(5), methyl orselinate(6), ficusol(7), and 4-(4-carboxy-2-methoxyphenoxy)-3,5-dimethoxybenzoic acid(8). Compound 1 was a new xanthone, and compound 4 was a xanthone dimer, compound 5 was a naphthoquinone. All compounds were isolated from this plant for the first time except compounds 2 and 3. Cytotoxic bioassay suggested that compounds 1, 2 and 4 possessed moderate cytotoxicity, suppressing HeLa cell line with IC_(50) va-lues of 24.3, 35.5 and 17.1 µmol·L~(-1), respectively. Compound 4 also could suppress K562 cells with an IC_(50) value of 39.8 µmol·L~(-1).

Prevalence of and factors associated with symptoms consistent with a diagnosis of irritable bowel syndrome among resident physicians in standardised training in China: a cross-sectional study.

OBJECTIVES: This study aims to investigate the incidence of and factors associated with irritable bowel syndrome (IBS) among resident physicians in standardised training at eight traditional Chinese medicine (TCM) hospitals in China. DESIGN: A cross-sectional survey was administered to resident physicians in their first to third years of standardised training at eight TCM hospitals. PARTICIPANTS AND SETTING: A total of 514 resident physicians in standardised training were included. MEASURES: The questionnaire consisted of two sections, namely: section A collected basic information, and section B included the four-item Perceived Stress Scale (PSS-4), the Patient Health Questionnaire-4 (PHQ-4), the Pittsburgh Sleep Quality Index (PSQI) and the Rome IV criteria for IBS. Univariate and multivariate logistic regression models were constructed to assess the associations of age, sex, body mass index, stress, depression, anxiety, sleep quality and IBS. RESULTS: Of the included resident doctors, 77.2% were female, 20.4% were obese or underweight and 8.6% had symptoms consistent with a diagnosis of IBS. There were no statistically significant differences in lifestyle factors (night shift work, overtime work or working efficiency during the COVID-19 pandemic) between patients with IBS and participants without IBS (hereafter, non-IBS participants) (p=0.429, p=0.572 or p=0.464, respectively). Notably, compared with non-IBS participants, patients with IBS had significantly higher mean scores on the PSS-4 and PHQ-4 (p=0.028 and p=0.012, respectively); however, there was not a significant difference in PSQI scores between these two groups (p=0.079). Depression symptoms were significantly associated with IBS (unadjusted OR 0.498, 95% CI 0.265 to 0.935, p=0.030). CONCLUSION: These findings suggest that IBS is common among resident physicians in standardised training. Future studies should investigate emotional distress, especially stress and depression, in the development of prevention or treatment of IBS.

[Research progress of mechanisms of acupuncture in treating slow transit constipation].

As an important part of the traditional Chinese medicine treatment system, acupuncture therapy has been used in the treatment of slow transit constipation (STC) for a long time and has achieved good clinical effects. This article reviews research on the effects of acupuncture therapy on STC published in recent years, focusing on the mechanism of acupuncture on the enteric nervous system, neurotransmitters, interstitial cells of Cajal, smooth muscle cells, gastrointestinal motility, psychological factors and intestinal microecology of STC, in order to provide reference for the clinical application and mechanism research of acupuncture in the treatment of STC in the future.

A new xanthone from hulls of Garcinia mangostana and its cytotoxic activity / 中国中药杂志

Eight compounds were isolated from ethyl acetate fraction of 80% ethanol extract of the hulls of Garcinia mangostana by silica gel, Sephadex LH-20 column chromatography, as well as prep-HPLC methods. By HR-ESI-MS, MS, 1D and 2D NMR spectral analyses, the structures of the eight compounds were identified as 16-en mangostenone E(1), α-mangostin(2), 1,7-dihydroxy-2-(3-methy-lbut-2-enyl)-3-methoxyxanthone(3), cratoxyxanthone(4), 2,6-dimethoxy-para-benzoquinone(5), methyl orselinate(6), ficusol(7), and 4-(4-carboxy-2-methoxyphenoxy)-3,5-dimethoxybenzoic acid(8). Compound 1 was a new xanthone, and compound 4 was a xanthone dimer, compound 5 was a naphthoquinone. All compounds were isolated from this plant for the first time except compounds 2 and 3. Cytotoxic bioassay suggested that compounds 1, 2 and 4 possessed moderate cytotoxicity, suppressing HeLa cell line with IC_(50) va-lues of 24.3, 35.5 and 17.1 μmol·L~(-1), respectively. Compound 4 also could suppress K562 cells with an IC_(50) value of 39.8 μmol·L~(-1).

[Chemical constituents from Salacia polysperma].

Nine compounds were isolated from the 90% ethanol extract of Salacia polysperma by silica gel, Sephadex LH-20 column chromatography, together with preparative HPLC methods. Based on HR-ESI-MS, MS, 1D and 2D NMR spectral analyses, the structures of the nine compounds were identified as 28-hydroxy wilforlide B(1), wilforlide A(2), 1ß,3ß-dihydroxyurs-9(11),12-diene(3),(-)-epicatechin(4),(+)-catechin(5),(-)-4'-O-methyl-ent-galloepicatechin(6), 3-hydroxy-1-(4-hydroxy-3-methoxy-phenyl)propan-1-one(7),(-)-(7S,8R)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7,9-diol-7'-aldehyde(8), and vanillic acid(9). Compound 1 is a new oleanane-type triterpene lactone. Compounds 1, 3, 4, 7-9 were isolated from the Salacia genus for the first time. All compounds were assayed for their α-glucosidase inhibitory activity. The results suggested that compound 8 exhibited moderate α-glucosidase inhibitory activity, with an IC_(50) value of 37.2 µmol·L~(-1), and the other compounds showed no α-glucosidase inhibitory activity.

Manual acupuncture benignly regulates blood-brain barrier disruption and reduces lipopolysaccharide loading and systemic inflammation, possibly by adjusting the gut microbiota.

Background: Blood-brain barrier (BBB) disruption and gut microbiota dysbiosis play crucial roles in Alzheimer's disease (AD). Lipopolysaccharide (LPS) stimulation triggered by gut microbial dysbiosis is an important factor in BBB disruption and systemic inflammation, but the mechanism of acupuncture regulation of BBB disruption via the gut microbiota in AD is not clear. Objective: The current study evaluated the effect of manual acupuncture (MA) on BBB dysfunction in APP/PS1 mice and examined the mechanism of gut microbiota by acupuncture in AD. Methods: Acupoints were applied to Baihui (GV20), Yintang (GV29), and Zusanli (ST36) in the MA group. Mice in the manual acupuncture plus antibiotics (MAa) group received antibiotics and acupuncture, while mice in the probiotics (P) group received probiotics. Alterations in spatial learning and memory, the gut microbiota, tightly connected structure and permeability of BBB, and the expression of LPS and inflammatory factors in each group were assessed. Results: Compared to the normal (N) group, cognitive ability was significantly impaired, the gut microbiota composition was markedly altered, the BBB was significantly disrupted, and the expression of LPS in serum and brain, serum TNF-α, and IL-1ß were significantly increased in the AD group (p < 0.01). These changes were inhibited in the MA and P groups (p < 0.01 or p < 0.05), and antibiotics reversed the benign regulatory effects of MA (p < 0.01 or p < 0.05). Conclusion: Manual acupuncture benignly modulated the gut microbiota and BBB dysfunction, reduced LPS, TNF-α, and IL-1ß. These effects were comparable to probiotics. The decrease in LPS load and systemic inflammation may play important roles in the regulation of BBB dysfunction by acupuncture, and the gut microbiota may be a potential target for the benign regulation of BBB disruption by acupuncture.

Benign regulation of the gut microbiota: The possible mechanism through which the beneficial effects of manual acupuncture on cognitive ability and intestinal mucosal barrier function occur in APP/PS1 mice.

Background: Gut microbiota dysbiosis and intestinal barrier injury play vital roles in Alzheimer's disease (AD) onset and development. Our previous studies have demonstrated that manual acupuncture (MA) could improve the cognitive abilities of APP/PS1 mice. However, the effect of MA on the intestinal mucosal barrier and the gut microbiota mechanism through which this effect occurs remain to be clarified. Methods: In the APP/PS1 manual acupuncture (Am) group, MA was applied in Baihui (GV20), Yintang (GV29), and Zusanli (ST36). Mice in the APP/PS1 antibiotic + manual acupuncture (Aa) group were treated with an antibiotic mixture and MA at the same time. Probiotics were delivered to the APP/PS1 probiotics (Ap) group. Alterations in spatial learning and memory, the gut microbiota, the intestinal barrier function, and the expression of glial fibrillary acidic protein (GFAP), lipopolysaccharide (LPS), and TNF-α were evaluated in each group. Results: Compared with the C57BL/6 control (Cc) group, cognitive ability was significantly decreased, the gut microbiota structure was obviously disrupted, intestinal barrier integrity was drastically impaired, and the intestinal inflammatory response was enhanced in the APP/PS1 control (Ac) group (P < 0.01). These changes were reversed by MA and probiotics (P < 0.01 or P < 0.05), whereas antibiotics inhibited the benign regulation by MA (P < 0.01 or P < 0.05). Conclusion: Manual acupuncture can benignly modulate gut microbiota dysbiosis, significantly reduce intestinal inflammation, and effectively alleviate the destruction of the intestinal mucosal barrier in APP/PS1 mice, and the effects are comparable to those of probiotics. The gut microbiota may play an important role in the improvement of the cognitive function and intestinal barrier function by MA.

Acupuncture for Patients With Chronic Tension-Type Headache: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Whether acupuncture is effective for chronic tension-type headache (CTTH) is inconclusive. We aimed to examine the effectiveness of acupuncture with a follow-up period of 32 weeks. METHODS: We conducted a randomized controlled trial, and 218 participants who were diagnosed with CTTH were recruited from June 2017 to September 2020. The participants in the intervention group received 20 sessions of true acupuncture (TA group) over 8 weeks. The acupuncture treatments were standardized across participants, and each acupuncture site was needled to achieve deqi sensation. Each treatment session lasted 30 minutes. The participants in the control group received the same sessions and treatment frequency of superficial acupuncture (SA group)-defined as a type of sham control by avoiding deqi sensation at each acupuncture site. The main outcome was the responder rate at 16 weeks after randomization (week 16) and was followed up at week 32. A responder was defined as a participant who reported at least a 50% reduction in the monthly number of headache days (MHDs). RESULTS: Our study included 218 participants (mean age: 43.1 years, mean disease duration: 130 months, MHDs: 21.5 days). The responder rate was 68.2% in the TA group (n=110) versus 48.1% in the SA group (n=108) at week 16 (odds ratio, 2.65; 95%CI, 1.5 to 4.77; p<0.001); and it was 68.2% in the TA group versus 50% in the SA group at week 32 (odds ratio, 2.4; 95%CI, 1.36 to 4.3; p<0.001). The reduction in MHDs was 13.1±9.8 days in the TA group versus 8.8±9.6 days in the SA group at week 16 (mean difference, 4.3 days; 95%CI, 2.0 to 6.5; p<0.001), and the reduction was 14±10.5 days in the TA group versus 9.5±9.3 days in the SA group at week 32 (mean difference, 4.5 days; 95%CI, 2.1 to 6.8; p<0.001). Four mild adverse events were reported; three in the TA group versus one in the SA group. CONCLUSION: The 8-week TA treatment was effective for the prophylaxis of CTTH. Further studies might focus on the cost-effectiveness of the treatment. TRIAL: Registration Information: ClinicalTrials.gov: NCT03133884 (https://clinicaltrials.gov/ct2/show/NCT03133884) CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that acupuncture (achieving deqi sensation) reduces mean headache days (per month) in patients with chronic tension-type headache.

Three new polyketides from vasR2 gene over-expressed mutant strain of Verrucosispora sp. NS0172.

Over-expression of the pathway specific positive regulator gene is an effective way to activate silent gene cluster. In the curret study, the SARP family regulatory gene, vasR2, was over-expressed in strain Verrucosispora sp. NS0172 and the cryptic gene cluster responsible for the biosynthesis of pentaketide ansamycin was partially activated. Two tetraketides (1 and 2) and a triketide (3) ansamycins, together with five known compounds (4-8), were isolated and elucidated from strain NS0172OEvasR2. Their NMR data were completely assigned by analysis of their HR-ESI-MS and 1H, 13C NMR, HMQC, HMBC and 1H-1H COSY spectra.

A brief discussion on evidence-based clinical research of traditional Chinese medicine.

BACKGROUND: The evaluation of clinical efficacy of traditional Chinese medicine (TCM) is the focus of the development of Chinese medicine, but at present there is no internationally recognized clinical efficacy evaluation system, which prevents TCM going abroad. Evidence-based medicine (EBM) research methods have achieved good results in the evaluation of TCM, but there are still some problems. How to use EBM methods in accordance with China's national conditions and develop evidence-based TCM that meets its own characteristics is the key to the current discussion. METHODS: Search websites such as PubMed, China National Knowledge Infrastructure, Wanfang Data and VIP by computer, and search papers related to evidence-based clinical research of TCM. RESULTS: A total of 15 high quality representative research papers published in internationally renowned journals were selected for example, including 4 randomized controlled trials (RCTs) related to Chinese medicine, 9 RCTs related to acupuncture, and 2 observational studies on the safety of TCM. CONCLUSIONS: EBM method is suitable for clinical research of TCM. There are differences between "disease" and "syndromes" in the use of TCM. Based on the further standardization of syndromes and classification of TCM, modern clinical research methods can be reasonably applied. However, the quality of clinical research related to TCM is not high, and there is a lack of research related to the safety of it, which should be paid attention to and improved in future research.

Shunt products of aminoansamycins from aas1 overexpressed mutant strain of Streptomyces sp. S35.

Constitutively expression of the pathway-specific activators is an effective method to activate silent gene clusters and improve natural product production. In this study, nine shunt products of aminoansamycins (1-9) were identified from a recombinant mutant strain S35-LAL by overexpressed the large-ATP-binding regulator of the LuxR family (LAL) gene aas1 in Streptomyces sp. S35. All the compounds showed no anti-microbial, anti-T3SS and cytotoxic activities.

[Systematic review and Meta-analysis of efficacy and safety of Compound Congrong Yizhi Capsules on vascular cognitive impairment].

To analyze the efficacy and safety of Compound Congrong Yizhi Capsules in treatment of vascular cognitive impairment. Databases, such as CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library, ClinicalTrials were electronically retrieved for relevant randomized controlled trials about the effect of Compound Congrong Yizhi Capsules in treatment of vascular cognitive impairment. Two researchers independently screened the literatures and extracted data according to the inclusion criteria, and used the risk of bias assessment tool in the Cochrane evaluation manual for quality assessment. The Cochrane systematic evaluation software RevMan 5.3 was used for data analysis. Totally 12 articles including 1 279 patients were included. The intervention measure was Compound Congrong Yizhi Capsules used alone or combined with Western medicine, and the control measure was the Western medicine alone or the blank control. According to the findings, for patients of vascular cognitive impairment no dementia, Compound Congrong Yizhi Capsules was better than the blank control in improving MoCA scale score and serum NO levels and reducing serum ET-1 levels. For vascular dementia patients, Compound Congrong Yizhi Capsules combined with Western medicine was better than Western medicine alone in improving MMSE and MoCA scale score. Five studies reported adverse events, but no significant adverse reaction was found. In conclusion, Compound Congrong Yizhi Capsules alone could alliviate early cognitive impairment in patients of vascular cognitive impairment no dementia; Compound Congrong Yizhi Capsules combined with Western medicine is superior to Western medicine alone in improving cognitive impairment. No obvious adverse reaction was found. Compound Congrong Yizhi Capsules can be recommended in clinical use. This conclusion needs to be further confirmed in high-quality clinical trials in the future.

[Clinical effect and safety of acupuncture in treatment of cardiac neurosis:a systematic review and meta-analysis].

OBJECTIVE: To systematically evaluate the clinical effect and safety of acupuncture in the treatment of cardiac neurosis. METHODS: Chinese databases (including SinoMed, VIP, CNKI, and Wanfang Data) and English databases (including PubMed and The Cochrane Library) were searched for randomized controlled trials (RCTs) on acupuncture in the treatment of cardiac neurosis published up to March 2019. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of included studies, and then RevMan 5.3 was used to perform a meta-analysis. RESULTS: A total of 7 RCTs were included, with 491 patients with cardiac neurosis. The results of the meta-analysis showed that compared with the conventional western medicine group, the acupuncture group had a significantly higher total effective rate (risk ratio ［RR］=1.16, 95% CI［1.05,1.28］, P=0.005) and had significantly greater improvements in Hamilton Anxiety Scale score (mean difference ［MD］=-3.22, 95% CI［-6.05, -0.39］, P=0.03). There were no significant differences between the two groups in Hamilton Depression Scale score (MD=-1.92, 95% CI［-4.76, -0.91］, P=0.18)，traditional Chinese medicine symptom score (MD=-5.49, 95% CI［-11.55, 0.56］, P=0.08), somatization symptom score (MD=-0.91, 95% CI［-3.28, 1.46］, P=0.45), and adverse reactions (RR=0.67, 95% CI［0.26,1.78］, P=0.42). CONCLUSION: Acupuncture can alleviate the symptoms and is safe in the treatment of cardiac neurosis.

[Efficacy of Shensong Yangxin Capsules in treating bradycardia combined with premature beat: a systematic review and Meta-analysis of randomized clinical trials].

To analyze the efficacy and safety of Shensong Yangxin Capsules in treatment of bradycardia combined with premature beat. Databases, such as CNKI, VIP, WanFang, SinoMed, PubMed, Cochrane Library, ClinicalTrials were retrieved by computers for relevant randomized controlled trials of Shensong Yangxin Capsules in treatment of bradycardia combined with premature beat. Two researchers independently screened out the literatures, extracted data according to the inclusion criteria, and applied the Risk of Bias assessment tool in assessing the methodological quality. The Cochrane systematic evaluation software RevMan 5.3 was used for data analysis. Totally 9 randomized controlled trials including 706 subjects were included. The intervention measure was the single administration with Shensong Yangxin Capsules, and the control measure was the blank control. The results showed that Shensong Yangxin Capsules had an obvious effect on average heart rate(MD=6.59, 95%CI[3.87, 9.31], I~2=90%), premature beat efficacy(RR=1.72, 95%CI[1.53, 1.93], I~2=0%), heart rate efficacy(RR=1.74, 95%CI[1.40, 2.17], I~2=47%), and objective efficacy(RR=1.50, 95%CI[1.31, 1.70], I~2=31%). Eight studies reported safety events, with no significant adverse reaction. In conclusion, the single administration with Shensong Yangxin Capsules may have a certain effect in improving heart rate, controlling premature beats and alleviating clinical symptoms in patients with bradycardia combined with premature beat, with no obvious adverse reaction. Shensong Yangxin Capsules can be used in clinic. This potential conclusion needs to be confirmed in future trials using rigorous methodology.

[Discussion on design of clinical trial scheme for doctor-patient co-construction of traditional Chinese medicine and Western medicine under concept of narrative medicine].

With the continuous improvement of modern medical technology, medical practice has become more and more procedural. The medical process is often dominated by doctors, while the value orientation of patients is often ignored, lacking effective communication between doctors and patients. In response to this phenomenon, Charon R proposed the concept of narrative medicine, which has been recognized by all walks of life. In recent years, the value of medical humanism has attracted more attention, and the research on narrative medicine at home and abroad is increasing gradually. But at present, most of the research on narrative medicine is in terms of theory, lacking clinical research. How to make narrative medicine applied in the real world is the focus of current research. Following the concept of narrative medicine, and taking the study on doctor-patient parallel medical record to evaluate the real clinical efficacy of traditional Chinese medicine(TCM) and Western medicine(WM) in the treatment of digestive diseases as an example, this study is to explore the design contents and key points of the clinical trial scheme of doctor-patient co-construction of TCM and WM under narrative medicine, and discuss the activity form and clinical efficacy evaluation method under narrative medicine. Clinical trial design includes four aspects: medicine, ethics, statistics and trial management. This study explored the design of the doctor-patient co-construction clinical trial scheme under narrative medicine from both theoretical and practical aspects, providing reference for the design and research of future doctor-patient co-construction scheme, and expecting to establish a better efficacy evaluation method of TCM and WM.

ACT001 modulates the NF-κB/MnSOD/ROS axis by targeting IKKß to inhibit glioblastoma cell growth.

Glioblastomas are high-grade brain tumors with poor prognoses, and new therapeutic approaches for these tumors are critically needed. This study revealed the underlying mechanisms of a new orphan drug, ACT001, that is currently in clinical trials for the treatment of advanced glioblastoma in Australia and China. ACT001 significantly suppressed glioma cell proliferation and induced apoptosis and cell cycle arrest in vitro, as determined by Cell Counting Kit-8 assays and flow cytometry. In addition, U-118 MG cells with high expression of p-IKKß were sensitive to ACT001. Changes in the oxidative stress pathway in U-118 MG cells were detected with the isobaric tags for relative and absolute quantitation (iTRAQ) method. We further verified that ACT001 elevated the levels of reactive oxygen species (ROS) by regulating NF-κB-targeted MnSOD. ACT001 markedly inhibited NF-κB activation by directly binding IKKß and inhibiting its phosphorylation. Overexpression of IKKß markedly attenuated the changes in MnSOD and NOX1, indicating that ACT001 increased the levels of ROS by reducing the protein expression of p-IKKß. Furthermore, ACT001 reduced cyclin B1/CDC2 expression and triggered G2/M phase arrest by increasing ROS production. ACT001 also upregulated the expression of Bax and Bim and induced apoptosis in a ROS-dependent manner. ACT001 effectively suppressed the growth of U-118 MG tumors in BALB/c nude mice and GL-261-luciferase tumors in C57BL/6 J mice. Finally, ACT001 downregulated the expression of p-p65, MnSOD, cyclin B1, CDC2, and Ki67 in U-118 MG tumor tissues. Patients with activated NF-κB signaling should thus be given priority for enrollment in future phase II clinical trials. KEY MESSAGES: ACT001 directly bind to IKKß and inhibited its phosphorylation. The inhibition of p-IKKß induced the generation of ROS. ACT001 promoted the generation of ROS by regulating MnSOD expression to induce G2/M phase arrest.

Identification of Parthenolide Dimers as Activators of Pyruvate Kinase M2 in Xenografts of Glioblastoma Multiforme in Vivo.

Herein we detail the discovery of a series of parthenolide dimers as activators of PKM2 and evaluation of their anti-GBM activities. The most promising compound 5 showed high potency to activate PKM2 with an AC50 value of 15 nM, inhibited proliferation and metastasis, and induced apoptosis of GBM cells. Compound 5 could promote tetramer formation of PKM2 and reduce nucleus translocation of PKM2 in GBM cells without influence on the expression of total PKM2, thereby inhibiting the STAT3 signal pathway in vitro and in vivo. PKM2 knockdown assay demonstrated that the anti-GBM effect of 5 mainly depended on the expression of PKM2 in vitro and in vivo. Compound 16, a prodrug of 5, markedly suppressed U118 tumor xenograft growth and reduced the weight of tumor. On the basis of these investigations, we propose that 16 might be considered as a promising lead compound for discovery of anti-GBM drugs.