Willingness to use acupuncture: Knowledge, attitudes, beliefs, and practices among allergic rhinitis patients.

This study aims to assess knowledge, attitudes, beliefs, and practices (KABP) among China mainland allergic rhinitis (AR) participants regarding their willingness to use acupuncture. Little is known about the understanding, attitudes, beliefs and practices of people with AR in China. A questionnaire was designed and administered to AR participants in mainland China to gather information about KABP regarding acupuncture use. A total of 324 valid questionnaires were collected from 30 provinces on the Chinese mainland. We recorded basic information and data about AR. The questionnaire designed according to KABP theory and with excellent reliability (Cronbach α coefficient: 0.725) and validity (KMO: 0.819). Knowledge: Fifty-five percent (179) of respondents reported knowing about acupuncture. The majority (172) knew that acupuncture was used for AR; 119 had received acupuncture for AR, and about 66% were aware of acupuncture. Attitudes and beliefs: Seventy percent of patients were willing to recommend acupuncture for AR to family and friends. Practice: Approximately 75% of respondents were willing to undergo acupuncture if they knew it was effective for AR. Approximately 25% of the respondents answered "Do it a few times and see how it works," "Do several treatments depending on how much they can afford," or "It is up to the doctor to decide". Correlation analysis: Those who identified with traditional Chinese medicine showed a robust willingness to recommend acupuncture for treating other diseases to family and friends (R = 0.718, P < .01) and a robust willingness to recommend acupuncture for AR to their families and friends (R = 0.564, P < .01). Acupuncture for AR has shown excellent awareness, recommendation and acceptance in mainland China. Efficacy, affordability, and trust in doctors were the 3 key factors that led respondents to choose acupuncture for their AR. Identification with traditional Chinese medicine culture significantly influenced attitudes, leading to AR recommendations and acceptance of acupuncture.

Metabolism of Paeoniae Radix Rubra and its 14 constituents in mice.

Objective: Paeoniae Radix Rubra (PRR) is a commonly used traditional Chinese medicine with the effects of clearing away heat, cooling the blood, and relieving blood stasis. To 1) elucidate the metabolites and metabolic pathways of PRR and its 14 main constituents in mice and 2) reveal the possible origins of the known effective forms of PRR and their isomers, the metabolism of PRR in mice was systematically studied for the first time. Methods: PRR and its 14 constituents were administered to mice by gavage once a day for seven consecutive days, respectively. All urine and feces were collected during the 7 days of dosing, and blood was collected at 1 h after the last dose. Metabolites were detected and identified using high performance liquid chromatography with diode array detector and combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry (HPLC-DAD-ESI-IT-TOF-MSn). Results: In total, 23, 16, 24, 17, 18, 30, 27, 17, 22, 17, 33, 3, 8, 24, and 31 metabolites of paeoniflorin, albiflorin, oxypaeoniflorin, benzoylpaeoniflorin, hydroxybenzoylpaeoniflorin, benzoyloxypaeoniflorin, galloylpaeoniflorin, lactiflorin, epicatechin gallate, catechin gallate, catechin, ellagic acid, 3,3'-di-O-methylellagic acid, methylgallate, and PRR were respectively identified in mice; after eliminating identical metabolites, a total of 195 metabolites remained, including 8, 11, 25, 17, 18, 30, 27, 17, 21, 17, 1, 2, 8, 20, and 20 newly identified metabolites, respectively. The metabolic reactions of PRR and its 14 main constituents in mice were primarily methylation, hydrogenation, hydrolysis, hydroxylation, glucuronidation, and sulfation. Conclusion: We elucidated the metabolites and metabolic pathways of PRR and its 14 constituents (e.g., paeoniflorin, catechin, ellagic acid, and gallic acid) in mice and revealed the possible origins of the 10 known effective forms of PRR and their isomers. The findings are of great significance to studying the mechanism of action and quality control of PRR.

A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study).

PURPOSE: To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription. RESULTS: The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70-1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only. CONCLUSIONS: High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation.

Effect of astragaloside IV and salvianolic acid B on antioxidant stress and vascular endothelial protection in the treatment of atherosclerosis based on metabonomics.

Vascular endothelial cells and oxidation reduction system play an important role in the pathogenesis of atherosclerosis (AS). If these conditions are disordered, it will inevitably lead to plaque formation and even rupture. Astragaloside IV (AsIV) and salvianolic acid B (Sal B) are the main active ingredients of Astragalus membranaceus and Salvia miltiorrhiza, respectively, and found to ameliorate vascular endothelial dysfunction and protect against oxidative stress in recent studies. However, it is still unknown if the combination of AsIV and Sal B (AsIV + Sal B) can inhibit the development of plaque through amplifying the protective effect of vascular endothelial cells and anti-oxidative stress effect. To clarify the role of AsIV + Sal B in AS, we observed the efficacy of each group (Control, Model, AsIV, Sal B, and AsIV + Sal B) by biomolecular assays, such as observing the pathological morphology of the aorta by oil red O staining, evaluating the level of oxidative stress and endothelial cells in the serum by the Elisa test, and analyzing the changes of all small molecule metabolites in liver tissue by UPLC-QTOF-MS. Results showed that AsIV, Sal B and AsIV + Sal B decreased the deposition of lipid in the arterial wall, so as to exert the effect of anti-oxidant stress and vascular endothelial protection, where the inhibitory effect of AsIV + Sal B was the most obvious. Metabonomics analysis showed that Sal B regulated the metabolic pathways of arginine and proline. AsIV regulated glycerol metabolism and saturated fatty acid biosynthesis metabolism. AsIV + Sal B is mainly related to the regulation of the citrate cycle (TCA cycle), alanine, aspartic acid, and glutamate metabolism, cysteine, and methionine metabolism. Succinic acid and methionine are synergistic metabolites that exert an enhancing effect when AsIV and Sal B were used in combination. In conclusion, we demonstrated that AsIV acompanied with Sal B can be successfully used for anti-oxidative stress and vascular endothelial protection of AS, and succinic acid and methionine are the synergistic metabolites.

Compassionate Use of Yuanjiang Decoction, a Traditional Chinese Medicinal Prescription, for Symptomatic Bradyarrhythmia.

Background: No effective medication is available for symptomatic bradyarrhythmia, particularly in low socioeconomic status (SES) population. Objective: To explore the safety and efficacy of Yuanjiang decoction, a traditional Chinese medicinal prescription, for symptomatic bradyarrhythmia on a compassionate-use basis. Methods: This compassionate-use study was conducted in Beijing, China between January 2019 and January 2020. Eligible participants were recruited and treated with Yuanjiang decoction (composed of 6 Chinese herbal medicines), 200 ml twice daily for 16 weeks. Analyses were done with the intention-to-treat (ITT) approach. The primary outcome measure was the proportion of participants who achieved a favorable treatment outcome at 16 weeks. Results: As of January 2020, 184 patients were included. After 16-weeks treatment, 12 participants were lost to contact while 21 participants were terminated from this study, with a drop-out rate of 17.93%. The most common treatment-related adverse events were xerostomia (6.52%), constipation (6.45%) and sleepiness (3.26%). The proportion of participants with favorable treatment outcome was 65.22% at 4 weeks, 59.78% at 8 weeks (OR: 1.11, 95% CI: 0.71-1.73), 61.41% at 12 weeks (OR: 1.16, 95% CI: 0.92-1.45) and 60.87% at 16 weeks (OR: 1.15, 95% CI: 0.98-1.35). In the multifactor regression analysis, the favorable treatment outcome at 16 weeks was significantly associated with completing at least 8 weeks treatment (OR: 2.053, 95% CI: 1.064-3.560), while unfavorable treatment outcome was significantly associated with an atrioventricular block (OR: 0.255, 95% CI: 0.083-0.784), current smoking (OR: 0.343, 95% CI: 0.027-0.487), and syncope in the month before treatment (OR: 0.321, 95%CI: 0.114-0.904). Conclusion: This compassionate-use study showed encouraging outcomes of treatment with Yuanjiang decoction, without serious adverse events. This study identified several key factors that may affect outcomes. These findings helped inform the design and assess the feasibility of a large-scale randomized clinical trial.

Based on proteomics to explore the mechanism of mecobalamin promoting the repair of injured peripheral nerves.

Mecobalamin is commonly used in the adjuvant intervention of various peripheral nerve injuries. Actin cytoskeleton plays a role in the regeneration of myelin and axon. Therefore, the purpose of this study was to explore the possibility of mecobalamin regulating actin cytoskeleton in repairing nerve injury. In this study, a crush injury on the right sciatic nerve of two groups of rats (12 in each group) was established. The control group was only given normal saline (i.g.), and the intervention group was given mecobalamin 1 mg/kg (i.g.). The rats were sacrificed on 28th day and the injured nerves were collected for proteomics. The result shows that regulation of actin cytoskeleton pathway changed significantly. The expression of protein Vav1 was verified by Western blot and immunofluorescence. In the intervention group, the nerve fiber structure was complete, the axons were dense and symmetrical, and the myelin sheath was compact and uniform in thickness. The positive rate of myelin basic protein and ßⅢ-tubulin was higher than that in the control group. The findings of the study show that mecobalamin regulates the actin cytoskeleton in the repair of nerve damage and upregulates Vav1 in the regulation of actin cytoskeleton pathway.

Combining electroacupuncture and transcranial direct current stimulation as an adjuvant therapy enhances spontaneous conversation and naming in subacute vascular aphasia: A retrospective analysis.

OBJECTIVE: Emerging evidence shows the effectiveness of speech and language therapy (SLT); however, precise therapeutic parameters remain unclear. Evidence for the use of adjunctive transcranial direct current stimulation (tDCS) to treat post-stroke aphasia (PSA) is promising; however, the utility of combining tDCS and electroacupuncture (EA) has not yet been analyzed. This study assessed the therapeutic consequences of EA and tDCS coupled with SLT in subacute PSA patients who were also undergoing hyperbaric oxygen therapy (HBOT). METHODS: A retrospective analysis was conducted on subacute (< 6 months) PSA patients who were divided into three groups: patients who received EA plus tDCS (acupuncture group), patients who underwent tDCS (tDCS group), and patients who experienced conventional therapy (HBOT + SLT). All subjects underwent 21 days of treatment and also received conventional treatment. The aphasia battery of Chinese (ABC) was used to score pre- and post-intervention status. RESULTS: The analysis comprised 238 patients. Cerebral infarction was the most frequent stroke type (137 [57.6%]), while motor (66 [27.7%]) and global aphasia (60 [25.2%]) were the most common types of aphasia. After 21 days of intervention, the ABC scores of all patients were improved. The acupuncture group had the highest ABC scores, but only repetition, naming, and spontaneous speech were statistically improved (P < 0.01). Post-hoc tests revealed significant improvement in word retrieval in the acupuncture and tDCS groups (P < 0.01, P = 0.037), while the acupuncture group had additional significant improvement in spontaneous conversation (P < 0.01). CONCLUSION: Combining acupuncture and tDCS as an adjuvant therapy for subacute PSA led to significant spontaneous speech and word retrieval improvements. Future prospective, multi-ethnic, multi-center trials are warranted.

[Effect of electroacupuncture on GLP-1R/PI3K/Akt protein pathway in mice with Parkinson's disease].

OBJECTIVE: To observe the effect of electroacupuncture(EA) on glucagon-like peptide-1 receptor (GLP-1R)/ phosphatidylinositol 3-kinase (PI3K)/ protein kinase B(Akt) protein pathway in the substantia nigra of mice with Parkinson's di-sease (PD)，so as to explore its underlying mechanisms in treatment of PD. METHODS: Forty-eight C57BL/6 male mice were randomly divided into normal, model, EA and inhibitor groups, with 12 mice in each group. PD mouse model was established by intragastrical administration of rotenone for 4 weeks. In the EA group, EA was applied at "Fengfu"(GV16), "Taichong"(LR3) and"Zusanli"(ST36) for 30 min, once daily, for 2 weeks. The mice of the inhibitor group received gavage of dipeptidyl peptidase-4 inhibitor ligliptin (10 mg·kg-1·d-1) once a day for 2 weeks. The behavioral scores of mice in each group were observed. The levels of tyrosine hydroxylase (TH) in serum and substantia nigra were detected by ELISA, and the protein relative expression levels of GLP-1R, phosphorylation of PI3K (p-PI3K) and phosphorylation of Akt (p-Akt) in substantia nigra of midbrain of mice were detected by Western blot. RESULTS: Compared with the normal group, the behavioral scores were significantly increased (P<0.01), TH levels in serum and substantia nigra, protein expression levels of GLP-1R, p-PI3K and p-Akt of the substantia nigra in the model group were significantly decreased (all P<0.01). After intervention and in comparison with the model group, the behavioral scores were significantly decreased (P<0.01), TH levels and the protein expression levels of GLP-1R, p-PI3K and p-Akt in both EA and inhibitor groups were significantly increased (all P<0.01). There were no significant differences in the abovementioned indexes between EA group and inhibitor group (all P>0.05), except for TH levels which were considerably down-regulated in the EA group relative to the inhibitor group (P<0.01, P<0.05). CONCLUSION: EA at GV16, LR3 and ST36 may increase the level of TH in serum and substantia nigra by up-regulating the activity of GLP-1R/PI3K/Akt protein pathway, and improve the behavioral performance of PD induced by rotenone.

Combining electroacupuncture and transcranial direct current stimulation as an adjuvant therapy enhances spontaneous conversation and naming in subacute vascular aphasia: A retrospective analysis / 中西医结合学报

OBJECTIVE@#Emerging evidence shows the effectiveness of speech and language therapy (SLT); however, precise therapeutic parameters remain unclear. Evidence for the use of adjunctive transcranial direct current stimulation (tDCS) to treat post-stroke aphasia (PSA) is promising; however, the utility of combining tDCS and electroacupuncture (EA) has not yet been analyzed. This study assessed the therapeutic consequences of EA and tDCS coupled with SLT in subacute PSA patients who were also undergoing hyperbaric oxygen therapy (HBOT).@*METHODS@#A retrospective analysis was conducted on subacute (< 6 months) PSA patients who were divided into three groups: patients who received EA plus tDCS (acupuncture group), patients who underwent tDCS (tDCS group), and patients who experienced conventional therapy (HBOT + SLT). All subjects underwent 21 days of treatment and also received conventional treatment. The aphasia battery of Chinese (ABC) was used to score pre- and post-intervention status.@*RESULTS@#The analysis comprised 238 patients. Cerebral infarction was the most frequent stroke type (137 [57.6%]), while motor (66 [27.7%]) and global aphasia (60 [25.2%]) were the most common types of aphasia. After 21 days of intervention, the ABC scores of all patients were improved. The acupuncture group had the highest ABC scores, but only repetition, naming, and spontaneous speech were statistically improved (P < 0.01). Post-hoc tests revealed significant improvement in word retrieval in the acupuncture and tDCS groups (P < 0.01, P = 0.037), while the acupuncture group had additional significant improvement in spontaneous conversation (P < 0.01).@*CONCLUSION@#Combining acupuncture and tDCS as an adjuvant therapy for subacute PSA led to significant spontaneous speech and word retrieval improvements. Future prospective, multi-ethnic, multi-center trials are warranted.

[Effects of ophiopogonin D on fatty acid metabolic enzymes in cardiomyocytes].

To explore the effect of ophiopogonin D on main fatty acid metabolic enzymes in human cardiomyocyte AC-16,so as to provide reference for cardiovascular protection mechanism and safe clinical application of Ophiopogon japonicus.CCK-8 (cell counting kit-8) was used to detect the effect of different concentrations of ophiopogonin D on the viability of cardiomyocytes.Meanwhile,the effect of different concentrations of ophiopogonin D on the morphology and quantity of cardiomyocytes was observed under microscope.The effect of ophiopogonin D on the mRNA expression of CYP2J2,CYP4F3,CYP4A11,CYP4A22 and CYP4F2 in cardiomyocytes was detected by RT-PCR.Western blot was used to detect the protein expression of CYP4F3 in different concentrations of ophiopogonin D.Compared with the control group,low-concentration ophiopogonin D had no effect on the viability of cardiomyocytes.However,ophiopogonin D with a concentration of higher than 20µmol·L~(-1)could promote the viability.Under the microscope,ophiopogonin D with a concentration of below 100µmol·L~(-1)had no significant effect on the morphology and number of cardiomyocytes.RT-PCR results showed that compared with the control group,5µmol·L~(-1)ophiopogonin D could slightly up-regulate mRNA expressions of CYP2J2 and CYP4F3,while high-concentration ophiopogonin D (10 and 20µmol·L~(-1)) could significantly induce mRNA expressions of CYP2J2and CYP4F3 in a dose-dependent manner (P<0.05).The same concentration of ophiopogonin D had a little effect on the mRNA expressions of CYP4A11,CYP4A22 and CYP4F2.Western blot results showed that 20µmol·L~(-1)ophiopogonin D could significantly induce the protein expression of CYP4F3 in a dose-dependent manner (P<0.05).Based on the above results,ophiopogonin D (less than100µmol·L~(-1)) has no effect on the viability of AC-16 cardiomyocytes.Ophiopogonin D (less than 100µmol·L~(-1)) can selectively induce the expressions of CYP2J2 and CYP4F3,regulate the metabolic pathway of fatty acid signaling molecules,and thus protecting the cardiovascular system.

Advances in Research on Pharmacological Effect of Astragaloside Ⅳ on Cardiovascular and Cerebrovascular Diseases / 中国实验方剂学杂志

Astragalus membranaceus has the effect of tonifying Qi and solid surface， diuretic support poison， discharging pus and astringent sores to produce muscle. It is not only used for syndromes such as deficiency of lung and temper， deficiency of spleen and diarrhea， but also for stroke， chest obstruction and other diseases. Due to the complex chemical composition and diverse pharmacological effect of Astragalus membranaceus， and the main role in invigorating qi and activating blood circulation has not been clarified. Astragaloside Ⅳ is one of its main active ingredients. In recent years， more and more studies on Astragaloside Ⅳ have been conducted at home and abroad. It has been reported that it has the medicinal value of enhancing immune function， strengthening heart and lowerin blood glucose， diuresis， anti-aging and anti-fatigue， et al， and has extensive pharmacological activity. Among them， the role of cardiovascular and cerebrovascular diseases in particular has attracted increasing attention. Cardiovascular and cerebrovascular diseases are ischemic or hemorrhagic diseases occurring in the heart， brain and systemic tissues due to blood viscosity， atherosclerosis， hypertension， hyperlipidemia， etc.， including cardiovascular and cerebrovascular diseases. Such diseases are a serious threat to mankind and are the leading cause of death worldwide. At present， western medicine is the main treatment， with many adverse reactions and poor long-term prognosis. TCM believes that the imbalance of qi and blood is the basic pathogenesis of this kind of disease. Qi deficiency and blood stasis are more common.At present， Astragaloside Ⅳ in the treatment of cardiovascular and cerebrovascular diseases in a number of studies， and achieved some results， but this review in recent years， Astragaloside Ⅳ in the treatment of cardiovascular and cerebrovascular diseases play the pharmacological activity， in order to explore whether Astragaloside Ⅳ is the main role of astragalus qi to find a theoretical basis for material basis， but also for the innovation of traditional Chinese medicine drug research and development of theoretical basis and practical guidance.

Differences in the Hemolytic Behavior of Two Isomers in Ophiopogon japonicus In Vitro and In Vivo and Their Risk Warnings.

Ophiopogonin D (OPD) and Ophiopogonin D' (OPD') are two bioactive ingredients in Ophiopogon japonicus. Previously published studies have often focused on the therapeutic effects related to OPD's antioxidant capacity but underestimated the cytotoxicity-related side effects of OPD', which may result in unpredictable risks. In this study, we reported another side effect of OPD', hemolysis, and what was unexpected was that this side effect also appeared with OPD. Although hemolysis effects for saponins are familiar to researchers, the hemolytic behavior of OPD or OPD' and the interactions between these two isomers are unique. Therefore, we investigated the effects of OPD and OPD' alone or in combination on the hemolytic behavior in vitro and in vivo and adopted chemical compatibility and proteomics methods to explain the potential mechanism. Meanwhile, to explain the drug-drug interactions (DDIs), molecular modeling was applied to explore the possible common targets. In this study, we reported that OPD' caused hemolysis both in vitro and in vivo, while OPD only caused hemolysis in vivo. We clarified the differences and DDIs in the hemolytic behavior of the two isomers. An analysis of the underlying mechanism governing this phenomenon showed that hemolysis caused by OPD or OPD' was related to the destruction of the redox balance of erythrocytes. In vivo, in addition to the redox imbalance, the proteomics data demonstrated that lipid metabolic disorders and mitochondrial energy metabolism are extensively involved by hemolysis. We provided a comprehensive description of the hemolysis of two isomers in Ophiopogon japonicus, and risk warnings related to hemolysis were presented. Our research also provided a positive reference for the development and further research of such bioactive components.

[Immediate effect of acupuncture and moxibustion at Guanyuan (CV 4) and Zusanli (ST 36) on heart rate variability in patients with qi deficiency syndrome].

OBJECTIVE: To compare the immediate effect of acupuncture and moxibustion at Guanyuan (CV 4) and Zusanli (ST 36) on heart rate variability index in patients with qi deficiency syndrome. METHODS: Ninety patients with qi deficiency syndrome were randomly divided into an acupuncture group, a moxibustion group and a blank group, 30 patients in each group. The patients in the acupuncture group were treated with acupuncture at Guanyuan (CV 4) and Zusanli (ST 36) for 15 min; acupuncture was given once. The patients in the moxibustion group were treated with moxibustion with identical acupoints and treatment duration. The patients in the blank group received no intervention. The symptom scores of qi deficiency syndrome in each group before and after treatment were recorded. The average heart rate and index of heart rate variability including total power, low frequency (LF), high frequency (HF) and logarithm of LF/HF (log LF/HF) were tested 5 min before treatment, 5 min, 10 min, 15 min into treatment, and 5 min after treatment. RESULTS: The symptom scores of qi deficiency syndrome were reduced in the acupuncture group and moxibustion group after treatment (P<0.05). Compared before treatment, in the acupuncture group, the HF was increased 5 min into treatment (P<0.05), but was reduced 15 min into treatment and 5 min after treatment (P<0.05, P<0.01). The log LF/HF was increased 5 min and 10 min into treatment and 5 min after treatment (P<0.01). The difference of average heart rate between 5 min before treatment and 5 min after treatment in the acupuncture group was higher than that in the moxibustion group and blank group (P<0.05), and the difference of log LF/HF was higher than that in the moxibustion group and blank group (P<0.05, P<0.01). CONCLUSION: Acupuncture and moxibustion has immediate effects on heart rate variability in patients with qi deficiency syndrome, and the effect of acupuncture is superior to moxibustion, which may be related to the benign regulation of acupuncture on autonomic nervous system.

[Simultaneous determination and analysis of amino acids and nucleosides in Dendrobium by UHPLC-QTRAP-MS/MS].

By using multivariate statistical analysis to evaluate essential quality, and provide scientific basis for their comprehensive utilization, we established an UHPLC-QTRAP-MS/MS method for the fast, precise, efficient determination of 21 kinds of amino acids and 10 kinds of nucleosides in different species of Dendrobium. The analysis was performed on a Waters XBridge Amide column(2.1 mm×100 mm,3.5 µm) with elution by mobile phase of 0.2% formic acid in water-0.2% formic acid in acetonitrile at a flow rate of 0.2 mL·min~(-1) with the column temperature at 30 ℃. The target compounds were analyzed by the positive ion multiple reaction monitoring(MRM) mode. The comprehensive evaluation of different species of Dendrobium was carried out by PCA and TOPSIS analysis. All 21 kinds of amino acids and 10 nucleosides showed good linearity among certain concentration range(r>0.999), the RSDs of the stability, precision, and repeatability tests were less than 3.0%. The recovery rate was in the range from 93.31% to 107.5%, and RSD was in the range of 1.1%-3.7%. The comprehensive evaluation index obtained with PCA showed that D. huoshanense was significantly higher than others regarding amino acids and D. officinale has higher nucleosides than other species. The biggest C_i difference of TOPSIS was 68.7%, and comprehensive evaluation showed that D. huoshanense produced the highest comprehensive quality. The method is precise, fast and efficient and can provide reliable basis for further researches and intrinsic quality control of Dendrobium.

Preferences heterogeneity of health care utilization of community residents in China: a stated preference discrete choice experiment.

BACKGROUND: To tackle the issue with the low usage of primary healthcare service in China, it is essential to align resource distribution with the preferences of the community residents. There are few academic researches for describing residents' perceived characteristics of healthcare services in China. This study aims to investigate the preferences of healthcare services utilization in community residents and explore the heterogeneity. The findings will be useful for the policy makers to take targeted measures to tailor the provision of healthcare services. METHODS: The face-to-face interviews and surveys were conducted to elicit four key attributes (care provider; mode of services; cost; travel time) of the preference from community residents for healthcare utilization. A rational test was presented first to confirm the consistency, and then 16 pairs of choice tasks with 12 sociodemographic items were given to the respondents. Two hypothetical options for each set, without an opt-out option, were presented in each choice task. The latent class analysis (LCA) was used to analyse the data. RESULTS: Two thousand one hundred sixty respondents from 36 communities in 6 cities were recruited for our study. 2019 (93.47%) respondents completed valid discrete choice experiment (DCE) questionnaires. The LCA results suggested that four groups of similar preferences were identified. The first group (27.29%) labelled as "Comprehensive consideration" had an even preference of all four attributes. The second group (37.79%) labelled as "Price-driven" preferred low-price healthcare services. The third group labelled as "Near distance" showed a clear preference for seeking healthcare services nearby. The fourth group (34.18%) labelled as "Quality seeker" preferred the healthcare service provided by experts. Willingness to pay (WTP) results showed that people were willing to accept CNY202.12($29.37) for Traditional Chinese Medicine (TCM) services and willing to pay CNY604.31($87.81) for the service provided by experts. CONCLUSIONS: Our study qualitatively measures the distinct preferences for healthcare utilization in community residents in China. The results suggest that the care provider, mode of services, travel time and cost should be considered in priority setting decisions. The study, however, reveals substantial disagreement in opinion of TCM between different population subgroups.

Effect of Astragali Radix Membranaceus in Promoting Blood Circulation and Its Modern Pharmacology Research / 中国实验方剂学杂志

Astragali Radix membranaceus is first recorded in Shennong Bencaojing, which has the effect in replenishing Qi and rising Yang, strengthening the body surface resistance, inducing diuresis to alleviate edema, and supporting for detoxication and tissue generation. As an essential medicine for invigorating Qi and invigorating the spleen, it is often used in diseases, such as Qi deficiency and fatigue, spleen deficiency diarrhea and so on, and has been well known by doctors. In recent years, scholars have a comprehensive understanding of the mechanisms in replenishing Qi, invigorating spleen and promoting water. However, Tao Hongjing first recorded that Astragali Radix membranaceus can " clear the evil blood between the five organs" . In Bencaojing Jizhu, this herbal medicine has the effect in promoting blood circulation at the same time. At present, traditional Chinese medicine often explains the mechanism of this herbal medicine in promoting blood circulation based on the theory of " replenishing Qi and activating blood circulation" and " blood circulation due to Qi circulation" , which however is not equivalent to the fact that this herbal medicine has no blood circulation effect. By summarizing the records of Astragali Radix membranaceus in the herbal literatures of the previous dynasties, it was found that its promoting blood circulation effect was widely used. In summary of the applications of traditional prescriptions and modern prescriptions in promoting blood circulation, Astragali Radix membranaceus can remove obstruction and activate blood circulation, activate blood and promote diuresis, activate blood circulation and strengthen the body resistance, which can best reflect the effect in activating blood circulation of this medicine. Modern pharmacology shows that Astragali Radix membranaceus has a good regulatory effect on the molecular mechanism of blood stasis pathological indexes by activating blood circulation. Due to no in-depth research, there is still room for study. Therefore, this paper thoroughly explores the mechanism of action of Astragali Radix membranaceus in promoting blood circulation by summarizing the effects of Astragali Radix membranaceus in literatures of previous dynasties and modern pharmacological studies, in order to expand the clinical application of Astragali Radix membranaceus and provide theoretical guidance for clinical treatment.

Role of Cellular Biomolecules in Screening, Diagnosis and Treatment of Colorectal Cancer.

BACKGROUND: Prevention is the primary strategy to avoid the occurrence and mortality of colorectal cancer. Generally, the concentrations of tumor markers tested during the diagnosis and believed to assist the detection of disease in the early stages of cancer. Some of the biomarkers are also important during treatment and real-time monitoring of the progress of treatment. METHODS: We considered a rationale search of key references from the database of peer-reviewed research and review literatures of colorectal cancer. The topic of search was focused on the novel methods and modern techniques of Screening, Diagnosis, and Treatment of colorectal cancer. The screened publications were critically analysed using a deductive content analysis and the matter was put in separate headings and sub headings. RESULTS: It was found that endoscopic examination, early detection, and surgery are some of the common strategies to manage colorectal cancer because late stages are difficult to treat due to the high-cost requirement and fewer chances of survival. As far as chemotherapy is concerned, systemic chemotherapy has been shown to offer the maximum benefit to patients with cancer metastasis. Among different chemotherapy measures, primary colorectal cancer prevention agents involve pharmaceuticals, phytochemicals, and dietary supplements are some of the standard options. CONCLUSION: In this review article, we have provided a comprehensive analysis of different biomarkers for the detection of colorectal cancer as well as different formulations developed for efficient treatment of the disease. The use of dietary supplements, the combinatorial approach, and nanotechnology-based strategies for colorectal cancer diagnosis and treatment are some of the recent and modern methods of cancer management.

Hesperetin derivative-12 (HDND-12) regulates macrophage polarization by modulating JAK2/STAT3 signaling pathway / 中国天然药物

Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as macrophage polarization, of which play an important role in the pathogenesis of many diseases. Numerous studies have proved that Hesperidin (HDN), a traditional Chinese medicine, extracted from fruit peels of the genus citrus, play key roles in anti-inflammation, anti-tumor, anti-oxidant and so on. However, the role of HDN in macrophage polarization has never been reported. Additional, because of its poor water solubility and bioavailability. Our laboratory had synthesized many hesperidin derivatives. Among them, hesperidin derivatives-12 (HDND-12) has better water solubility and bioavailability. So, we evaluated the role of HDND-12 in macrophage polarization in the present study. The results showed that the expression of Arginase-1 (Arg-1), interleukin-10 (IL-10), transforming growth factor β (TGF-β) were up-regulated by HDND-12, whereas the expression of inducible Nitric Oxide Synthase (iNOS) was down-regulated in LPS- and IFN-γ-treated (M1) RAW264.7 cells. Moreover, the expression of p-JAK2 and p-STAT3 were significantly decreased after stimulation with HDND-12 in M1-like macrophages. More importantly, when we taken AG490 (inhibitor of JAK2/STAT3 signaling), the protein levels of iNOS were significantly reduced in AG490 stimulation group compare with control in LPS, IFN-γ and HDND-12 stimulation cells. Taken together, these findings indicated that HDND-12 could prevent polarization toward M1-like macrophages, at least in part, through modulating JAK2/STAT3 pathway.

[Effect of six components in Polygoni Multiflori Radix on regulation of CYP3A4 mediated by human pregnane X receptor].

This paper aimed to study the six chemical components of Polygoni Multiflori Radix (gallic acid, quercetin, luteolin, kaempferol, resveratrol, apigenin). By the established pregnane X receptor (human pregnant X receptor, PXR) CYP3A4 mediated drug induced rapid screening technique, the effect of chemical components on the cell activity was detected by MTS cell method, and the value of IC50 was calculated. The dual luciferase reporter system was used to co-transfect PXR reporter gene expression vector containing transcriptional regulation and CYP3A4 with HepG2 cells, with 10 µmol·L⁻¹ rifampicin (RIF) as a positive control, and 10 µmol·L⁻¹ of ketoconazole (TKZ) as negative control. Gallic acid, quercetin, luteolin, kaempferol, apigenin, resveratrol(5, 10, 20 µmol·L⁻¹) were used to incubate for 24 h, and the luciferase activity was detected. The results showed that when plasmid pcDNA3.1 was co-transfected with pGL4.17-CYP3A4, gallic acid and resveratrol had an inhibitory effect on the regulation of CYP3A4, and quercetin, luteolin, kaempferol had an inductive effect on CYP3A4; when pcDNA3.14-PXR was co-transfected with pGL4.17-CYP3A4, quercetin, luteolin, kaempferol, apigenin, resveratrol had an inductive effect. To sum up, the 6 reported liver injury components had inhibitory or activating effects on CYP3A4. After PXR plasmid was involved, 5 components had an inductive effect on CYP3A4, and the inductive effects of 2 components were significantly different. In this experiment, we found that 2 kinds of potential liver injury components in Polygoni Multiflori Radix had been induced by CYP3A4, which was achieved through PXR regulation. It suggested that attention shall be paid to potential drug interactions when combined with Polygoni Multiflori Radix, so as to improve the safety and efficacy.

[Complex enzyme combined with ultrasound extraction technology, physicochemical properties and antioxidant activity of Hedysarum polysaccharides].

In this study, complex enzymes combined with ultrasonic extraction technology（MC） were used, to select optimal extraction combinations by single factor and orthogonal test, with Hedysarum polysaccharides yield and content as the comprehensive indexes. The components, physicochemical properties and antioxidant activity of Hedysarum polysaccharides from complex enzyme combined with ultrasonic extraction（HPS-MC）and the Hedysarum polysaccharides from hot water extraction（HPS-R）were analyzed. The results showed that：complex enzymes had significant effect on the yield and content of Hedysarum polysaccharides, and the ultrasonic power could significantly improve the content of Hedysarum polysaccharides. The optimum technological parameters were as follows: complex enzyme ratio 1:1, ultrasonic power 105 W, ultrasonic time 60 min, and enzymatic hydrolysis pH 5, achieving （14.01±0.64）% and （92.45±1.47）% respectively for the yield and content of Polysaccharides. As compared with HPS-R, the molecular weight, absolute viscosity and protein content of HPS-MC were decreased, while the content of uronic acid was increased. In the antioxidant system, the concentration of polysaccharide was within the range of 1-7 g·L⁻¹; the antioxidant activity of HPS-MC was higher than that of HPS-R, and HPS-MC (80%) with the lowest molecular weight showed a significant dose effect relationship with the increase of the experimental concentration. In conclusion, MC is a simple, convenient, economical and environmentally friendly extraction technology, and the Hedysarum polysaccharides extracted by this method have obvious antioxidant activity.