New 5-methyl-4-hydroxycoumarin polyketide derivatives from Gerbera delavayi with anti-inflammatory activity.

Five new 5-methyl-4-hydroxycoumarin polyketide derivatives (MPDs), delavayicoumarins A-E (1-5), were isolated from the whole plants of Gerbera delavayi. Among them, compounds 1-3 are the common monoterpene polyketide coumarins (MPCs), while 4 is a modified MPC with both the lactone ring contracted to a five-membered furan ring and a carboxyl at C-3, and 5 is a pair of unusual phenylpropanoid polyketide coumarin enantiomers (5a and 5b), featuring a phenylpropanoid unit at C-3. The planar structures were elucidated by spectroscopic methods and biosynthetic arguments, and the absolute configurations of 1-3, 5a and 5b were confirmed by calculated electronic circular dichroism (ECD) experiment. Furthermore, compounds 1-3, (+)-5 and (-)-5 were tested for the nitric oxide (NO) inhibitory activity by using lipopolysaccharide (LPS)-induced RAW 264.7 cells in vitro. The results showed that compounds 1-3, (+)-5 and (-)-5 remarkably inhibited NO production at the concentration of 10.0 µM, exhibiting that they have significant anti-inflammatory activity.

Effectiveness and Safety of Chinese Medicine at Shenque (CV 8) for Primary Dysmenorrhea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Primary dysmenorrhea (PD) is the most common complaint associated with menstruation and affects up to three-quarters of women at some stage of their reproductive life. In Chinese medicine, navel therapy, treatment provided at Shenque (CV 8), is used as a treatment option for PD. OBJECTIVE: To evaluate the effect of navel therapy on pain relief and quality of life in women with PD, compared with Western medicine (WM). METHODS: China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), SinoMed and Wanfang Database, MEDLINE, the Cochrane Library, Embase, Web of Science, and the International Clinical Trial Registry of the U.S. National Institutes of Health were searched from their inceptions to April 1, 2021. Randomized controlled trials (RCTs) assessing therapeutic effects of navel therapy on PD were eligible for inclusion. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool. RESULTS: Totally 24 RCTs involving 2,614 participants were identified. Interventions applied to acupuncture point CV 8 included: herbal patching, moxibustion or combined navel therapy (using at least 2 types of stimulation). Compared to placebo, there was a significant effect in favor of navel therapy on reducing overall menstrual symptom scores at the end of treatment [mean difference: -0.82, 95% confidence interval (CI): -1.00 to -0.64, n=90; 1 RCT]. As compared with Western medicine, navel therapy had a superior effect on pain intensity as assessed by Visual Analogue Scale at the end of treatment [standardized mean difference (SMD): -0.64, 95% CI: -1.22 to -0.06, I2=80%, n=262; 3 RCTs]; on symptom resolution rate at 3-month follow-up (risk ratio: 1.94, 95% CI: 1.47 to 2.56, n=1527, I2=38%; 13 RCTs); and on global menstrual symptoms score at the end of treatment (SMD: -0.67, 95% CI: -0.90 to -0.45, I2=63%, n=990; 12 RCTs). Subgroup analyses showed either a better or an equivalent effect comparing navel therapy with Western medicine. No major adverse events were reported. The methodological quality of included trials was poor overall. CONCLUSIONS: Navel therapy appears to be more effective than Western medicine in decreasing menstrual pain and improving overall symptoms of PD. However, these findings need to be confirmed by well-designed clinical trials with adequate sample size (Systematic review registration at PROSPERO, No. CRD42021240350).

[Meta-analysis of Bailing Capsules in improvement of microinflammation and nutritional status among maintenance hemodialysis patients].

This Meta-analysis was designed to evaluate the effects of Bailing Capsules on microinflammation and nutritional status of maintenance hemodialysis patients, and to determine its efficacy and safety. The randomized controlled trials concerning the intervention of microinflammation and nutritional status in maintenance hemodialysis patients with Bailing Capsules were searched from Chinese and English databases including CNKI, Wanfang, VIP, PubMed, EMbase, and Cochrane Library. A total of 16 articles were obtained, involving 1 095 cases. As revealed by Meta-analysis,(1)Bailing Capsules lowered the levels of serum high sensitivity C-reactive protein(SMD=-0.92, 95%CI[-1.05,-0.80], P<0.000 01), interleukin-6(SMD=-1.49, 95%CI[-1.96,-1.02], P<0.000 01), and tumor necrosis factor-α(SMD=-1.48, 95%CI[-1.68,-1.28], P<0.000 01) in patients with maintenance hemodialysis, thus alleviating microinflammation.(2)Bailing Capsules elevated the levels of serum hemoglobin(SMD=1.37, 95%CI[1.21, 1.54], P<0.000 01), albumin(SMD=0.78, 95%CI[0.57, 0.98], P<0.000 01), and triglyceride(SMD=0.29, 95%CI[0.07, 0.50], P=0.01) in patients with hemodialysis to improve their nutritional status.(3)Bailing Capsules reduced the incidence of cardiovascular events(RR=0.45, 95%CI[0.34, 0.59], P<0.000 01).(4)A total of six patients presented with mild gastrointestinal discomfort after receiving Bailing Capsules, and no serious adverse reactions were observed. The sequential analysis showed that the sample size of this Meta-analysis had reached the expected value. Meanwhile, the grade of evidence quality suggested that the outcome indicators were mainly low or extremely low in quality. In conclusion, Bailing Capsules might have potential advantages in alleviating microinflammation, improving nutritional status, and reducing the incidence of cardiovascular events. However, in view of the low quality and evidence of the included literature, high-quality clinical trials are needed to further confirm the efficacy and safety of Bailing Capsules.

Reynoutria japonica Houtt for Acute Respiratory Tract Infections in Adults and Children: A Systematic Review.

Introduction: Respiratory tract infections (RTIs) are a major cause of morbidity and mortality in some high-risk groups including children and older adults. There is evidence that Chinese herbal medicine has an effect on RTIs. Reynoutria japonica Houtt (better known under its synonym Fallopia japonica (Houtt.) Ronse Decr.) (F. japonica), a commonly used Chinese herbal medicine, has a high content of resveratrol and glycosides. In traditional Chinese medicine theory, F. japonica has the effect of clearing heat in the body, improving blood and qi circulation, eliminating phlegm, and relieving cough, so it may have an effect on RTIs. Methods: This systematic review was registered under PROSPERO CRD42020188604. Databases were searched for randomized controlled trials of F. japonica as a single herb, or as a component of a complex herbal formula for RTIs. Quality of methodology was assessed by two reviewers independently using the Cochrane Risk of Bias Tool. The primary outcome was symptom improvement rate. The secondary outcome measures were fever clearance time, Murray lung injury score and incidence of adverse effects. The extracted data were pooled and meta-analysed by RevMan 5.3 software. Results: Eight RCTs with 1,123 participants with acute RTIs were included in this systematic review, and all the RCTs used F. japonica as part of a herbal mixture. Only one included trial used F. japonica in a herbal mixture without antibiotics in the treatment group. The findings showed that herbal remedies that included F. japonica could increase the symptom improvement rate (risk ratio 1.14, 95% confidence intervals [1.09, 1.20], I2 = 0%, p < 0.00001, n = 7 trials, 1,013 participants), shorten fever duration, reduce Murray lung injury score and did not increase adverse events (RR 0.33, 95% CI [0.11, 1.00], I2 = 0%, p = 0.05, n = 5 trials, 676 participants). Conclusion: There is limited but some evidence that F. japonica as part of a herbal mixture may be an effective and safe intervention for acute RTIs in clinical practice. In future studies it would be preferable to evaluate the effectiveness and safety of using F. japonica without antibiotics for acute RTIs.

Buzhong Tiaogan Formula for delaying colorectal liver metastasis (liver depression spleen deficient type): A multicenter randomized controlled trial: A study protocol.

INTRODUCTION: Colorectal cancer has been ranked third among the most common cancers worldwide and raised to the second leading cause of cancer death with nearly one-tenth of cancer-related deaths globally, and nearly half of colorectal cancer patients present with or develop colorectal cancer liver metastasis (CRLM). Buzhong Tiaogan Formula (BTF) has been proven to treat CRLM in our team, but there are lacking of evidence on its effective in delaying colorectal liver metastasis (liver depression spleen deficiency type), so we will evaluate the efficacy and safety of BTF in preventing the occurrence of CRLM. METHODS: This randomized controlled trial (RCT) will be carried out in 3 different hospitals in Shanxi Province planning to recruit 150 CRLM patients with the type of liver depression spleen deficiency. The control group will be treated by basic antitumor therapy and the treatment group will use BTF plus basic antitumor therapy. The primary outcomes will be quality of life of included patients, the time of occurrence of liver metastasis, the score of traditional Chinese medicine symptom for the type of liver depression spleen deficiency; and the secondary outcomes will include overall survival, progression-free survival, DFS, tumor microenvironment and immune state of the included patient. Safety evaluation will be recorded during the whole study. All data in this RCT will be analyzed by SPSS 23.0 software. This study has been approved by the Clinical Research Ethics Committee of Shanxi Province Hospital of Traditional Chinese medicine (2021Y-06016). DISCUSSION: The results of this RCT will contribute to BTF for delaying colorectal liver metastasis (liver depression spleen deficient type). And the results from this RCT will be published in a relevant journal after finished. TRIAL REGISTRATION: ChiMCTR2100005268 (September 4, 2021).

The efficacy and safety of modified Gegenqinlian Fomular for advanced colorectal cancer (damp heat accumulation type): A multicenter randomized controlled trial.

INTRODUCTION: CRC, the incidence of the fourth highest among males and the third among females, is one of the malignant tumors that seriously threaten human health. The principle of treatment for advanced stage CRC is a multidisciplinary and comprehensive treatment based on chemotherapy, which always bring significant toxic side effects. CHM has advantages in the treatment of tumors with the effect on improving clinical symptoms and reducing side effects. GGQL formula is mainly used for treating abnormal defecates caused by damp-heat, so we will evaluate the clinical efficacy and safety of modified GGQL formula for patients with advanced CRC with the type of damp-heat in this study. METHODS: Multicenter RCT with two parallel groups in three hospitals planning to recruit 120 CRC patients with the type of damp-heat will be conducted. The control group will be treated by basic antitumor therapy and the treatment group will use modified GGQL formula plus basic antitumor therapy. The primary outcomes will be quality of life, TCM symptom score, PFS and OS, and the secondary outcomes will be performance status, size of tumor, tumor marker in the serum, tumor microenvironment and immune status. All analyses will be based on an intention-to-treat principle. This study was approved by the Human Research Ethics Committee of Shanxi Province Hospital of Traditional Chinese medicine (2021Y-06017). The results will be published in relevant journal. DISCUSSION: The results of this RCT will contribute to Chinese herbal medicine for treating CRC patients with the type of damp heat accumulation. TRIAL REGISTRATION: ChiCTR2100050754 (September 4, 2021).

Electroacupuncture Improves Clearance of Amyloid-ß through the Glymphatic System in the SAMP8 Mouse Model of Alzheimer's Disease.

Background: Memory loss and cognitive impairment characterize the neurodegenerative disorder, Alzheimer's disease (AD). Amyloid-ß (Aß) is the key factor that triggers the course of AD, and reducing the deposition of Aß in the brain has been considered as a potential target for the treatment of AD. In clinical and animal studies, electroacupuncture (EA) has been shown to be an effective treatment for AD. In recent years, substantial evidence has accumulated suggesting the important role of the glymphatic system in Aß clearance. Objective: The purpose of this study was to explore whether EA modifies the accumulation of Aß through the glymphatic system and may thus be applied to alleviate cognitive impairments. Methods: Seven-month-old SAMP8 mice were randomized into a control group (Pc) and an electroacupuncture group (Pe). Age-matched SAMR1 mice were used as normal controls (Rc). Mice in the Pe group were stimulated on Baihui (GV20) and Yintang (GV29) for 10 min and then pricked at Shuigou (GV26) for ten times. EA treatment lasted for 8 weeks. In each week, EA would be applied once a day for the first five consecutive days and ceased at the remaining two days. After EA treatment, Morris water maze (MWM) test was used to evaluate the cognitive function; HE and Nissl staining was performed to observe the brain histomorphology; ELISA, contrast-enhanced MRI, and immunofluorescence were applied to explore the mechanisms underlying EA effects from Aß accumulation, glymphatic system function, reactivity of astrocytes, and AQP4 polarization, respectively. Results: This EA regime could improve cognition and alleviate neuropathological damage to brain tissue. And EA treatment might reduce Aß accumulation, enhance paravascular influx in the glymphatic system, inhibit the reactivity of astrocytes, and improve AQP4 polarity. Conclusion: EA treatment might reduce Aß accumulation from the brain via improving clearance performance of the glymphatic system and thereby alleviating cognitive impairment.

Bupleuri radix for Acute Uncomplicated Respiratory Tract Infection: A Systematic Review of Randomized Controlled Trials.

Objective: To evaluate the efficacy, clinical effectiveness, and safety of the Chinese herb Bupleuri radix for the treatment of acute uncomplicated respiratory tract infections (ARTIs). Methods: Four English and four Chinese databases were searched from their inception to June 2021. Randomized controlled trials (RCTs) assessing therapeutic effects of Bupleuri radix on ARTI were eligible for inclusion. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. RevMan 5.4 software was used for data analyses with effects estimated as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). The certainty of the evidence was assessed using the online GRADEpro tool. Results: Seven randomized trials involving 910 patients with acute upper respiratory tract infection (AURTI) were included. The review identified Bupleuri radix agents with four administration routes (oral, acupoint injection, intramuscular injection, nebulized inhalation). Bupleuri radix acupoint injection compared with placebo showed statistically significant effects in reducing fever resolution time (MD: -33.32 h, 95%CI: -35.71, -30.93), and in increasing the proportion of participants with fever resolved within 48 h from treatment onset (RR: 14, 95%CI: 1.96, 99.94). Bupleuri radix acupoint injection combined with usual care is more effective in reducing the temperature at day 1 from treatment onset (MD: -1.00°C, 95%CI: -1.19, -0.81) compared with usual care alone. Bupleuri radix pills showed similar antipyretic effects to acetaminophen. However, Bupleuri radix intramuscular injection plus vitamins failed to demonstrate an effect in reducing fever, when compared with ribavirin plus vitamins. It suggested that oral administration of Bupleuri radix solution for injections, pills, and Bupleuri radix decoction have a similar effect on improving global AURTI symptoms including two key symptoms (nasal discharge and cough), when compared with usual care alone. Only two trials reported whether or not there were any AEs and found no occurrence of adverse events in the herbal group. Conclusion: Low-certainty or very low-certainty evidence demonstrated that Bupleuri radix (solution for injections and pills) has an antipyretic effect on febrile patients with AURTI, but it has no effect on other AURTI symptoms. However, these findings need to be further confirmed by well-designed clinical trials with adequate sample sizes. Systematic review registration: (https://www.crd.york.ac.uk/prospero/#recordDetails), PROSPERO registration number: CRD42021234066.

[Characteristics of seed rain on abandoned slopes in the hilly-gullied Loess Plateau, Northwest China].

The objective of this study was to analyze the dynamic characteristics of seed rain on abandoned slopes in the hilly-gullied Loess Plateau region and identify the relationship between seed rain and standing vegetation. Three abandoned slopes were chosen as sampling sites in Zhifanggou watershed. Thirty traps were installed at each site to collect seed rain from October 2010 to April 2013. Standing vegetation was surveyed to identify dominant species in August 2011 and 2012, respectively. Thirty-seven species belonging to seventeen families were identified in the seed rain, and the dominant species, i.e., Lespedeza davurica, Astragalus scaberrimus, Setaria viridis, Cleistogenes squarrosa, Stipa bungeana, Bothriochloa ischcemum, Artemisia scoparia, A. gmelinii, and Heteropappus altaicus, took up to 95.8% of the total seed rain. Three species in seed rain were not found in the standing vegetation. The Sorensen similarity index between seed rain and standing vegetation was 0.77. Seed rain densities were 3737 and 6449 seeds · m(-2) in May 2011-April 2012 and May 2012-April 2013, respectively, and alternate bearing existed. During the study period, seed rain from different positions varied from 3853 to 37923 seeds · m(-2) and belonged to 7-15 species. The results indicated the space limitation of seed dispersal. Seed rain densities were in the middle of the pack compared with similar ecosystems in other studies. High temporal and spatial heterogeneity of seed rain was observed because of rainfall, microtopography and so on.

Flax seed oil inhibits metastatic melanoma and reduces lung tumor formation in mice.

PURPOSE: Cancer is one of the leading causes of mortality worldwide. Tumor cells circulating in the blood evidence the migration of tumor from the site of origin to another site leading to the formation of new metastatic lesion and establishment of metastatic tumors. In the present study, cultured metastatic tumor cells were injected into the C57BL/6 mice through tail-vein injection (TVI) and the anti-metastatic properties of flax seed oil (FSO) were evaluated. METHODS: Pre-administration of FSO in a dose of 0.3 ml/mice/day was performed for 15 days. On 16th and 21st day, mice were challenged with 2x105 /100 µl murine B10 melanoma (YAC-1 suspended in sterile PBS) cells and continued with FSO administration until the end of the experimental period (40 days) to assess the effect on lung metastasis. At the end of experimental period, mice were sacrificed for plasma and lung tissue samples for biochemical and marker studies. Activities of marker enzymes (AST and ALT), enzymic antioxidants (superoxide dismutase/SOD and catalase/CAT), levels of non/enzymic antioxidants (glutathione), oxidation/stress marker (malondialdehyde/MDA) and cytokines (TNF-alpha, IL-2, IFN-gamma and MMP-9) were assessed. RESULTS: Elevated marker enzyme activities in serum and altered enzymic and non-enzymic antioxidants were recovered during FSO treatment. Altered metastatic markers levels favoring the formation of metastatic lesions were observed in the disease group. FSO administration re-altered the levels of these markers in the treatment group contributing to better control of metastasis development. CONCLUSION: These results support the protective role of FSO against lung cancer metastasis.