OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Aim To investigate the mechanisms of Ke-chuanting granules(KCT)inhibiting the IL-33/ILC2s pathway and pathogenic T cells to intervene in allergic airway inflammation.Methods Network pharmacolo-gy was utilized to analyze the potential targets and mechanisms of KCT-treated asthma.Allergic asthma models were induced in mice using OVA.Lung histo-pathology was conducted to observe injury changes.ELISA and quantitative PCR were utilized to measure key inflammatory factors and their mRNA expression levels in Th2-type asthma.Western blot was used to detect the phosphorylation levels of relevant proteins in the MAPK pathway.Flow cytometry was performed to evaluate the proportions of ILC2s,Th1,Th 17,Th2 and Treg cells.Results Network pharmacology iden-tified 227 main active components and 143 key targets of KCT in treating asthma,primarily enriched in signa-ling pathways such as MAPK and IL-17.Further vali-dation experiments demonstrated that KCT significantly alleviated lung inflammatory injury in asthmatic mice,reduced the number of B cells,production of I L-4,TNF-α and TGF-β,downregulated JNK phosphoryla-tion levels in lung tissue,as well as mRNA levels of Il-33,Bcl11b,Rorα,Tcf-7,Jun,Mapk3 and Mapk14.KCT intervention reduced the numbers of ILC2s and Th 17 cells in lungs and spleens of mice,and inhibited Th2 cell infiltration in lungs.Conclusions KCT ex-hibits therapeutic effects on allergic airway inflamma-tion in asthma,closely associated with the inhibition of the IL-33/ILC2s pathway,pathogenic T cell subsets,and JNK-MAPK signaling pathway.

Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived car-diomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a po-tential reagent for repairing damaged hearts.

Aim To develop an LC-MS/MS method for the determination of prucalopride(PCP)in human plasma.Methods Prucalopride -13CD3(dPCP)was used as the internal standard.The analytes were extracted from human plasma through liquid-liquid extraction method using ethyl acetate, followed by being dried, and then the reconstitution was injected into LC-MS/MS systems.Agilent ZORBAX SB C18(3.0×100 mm, 3.5 μm)column and isocratic elution system composing of methanol and 1 mmol·L-1 ammonium acetate(80:20, V/V)provided chromatographic separation of PCP and dPCP.AB Sciex API4000 mass spectrometer equipped with an electrospray ionization source in positive ion mode was employed for mass detection, and data acquisition was carried out in multiple reaction monitoring(MRM)mode.The mass transition ion-pair was followed as m/z 368.4/196.0 for PCP and m/z 374.4/198.0 for dPCP.Results PCP and dPCP were eluted at 3.6 min, with no interference in human blank plasma.PCP in human plasma showed good linearity over the concentration range of 0.058 96-7.547 μg·L-1 with the correlation coefficient of 0.996 3-0.999 6.The lower limit of quantitation of this method was 0.058 96 μg·L-1.The intra-batch and inter-batch accuracy ranged from 98.29% to 108.2%, with good precision(CV<5.2%).The average matrix factors of normal, haemolysed and lipaemic matrix human samples all ranged from 96.48% to 106.3% with CV less than 8.39%.The average extraction recoveries of PCP at low, medium and high concentrations were 89.88%, 95.27% and 94.52% respectively, with CV less than 7.21%.PCP was stable in human samples after 6 h at room temperature, 60 h at -20 ℃, 56 days or three freeze-thaw cycles at -80 ℃; meanwhile, the processed plasma samples remained stable after being stored for 24 hours in autosampler at 8 ℃.Furthermore, PCP in human blood samples was proved to be stable after 4 h at room temperature.Conclusions The present LC-MS/MS method for the determination of PCP in human plasma was convenient, accurate, sensitive, stable, specific and reproducible and was proved to be suitable for the clinical pharmacokinetics and bioequivalence studies of PCP preparations.

OBJECTIVE: To observe the effect of five-element music therapy of traditional Chinese medicine (TCM) on the clinical symptoms and the quality of life in the patients with suboptimal health status (SHS) of liver stagnation and spleen deficiency and explore the corresponding specificity changes in the temperature of acupoints when zangfu functions are of dysfunction and recovered to be balanced, separately. METHODS: Sixty patients with SHS of liver stagnation and spleen deficiency were randomized into an observation group and a control group, 30 cases in each one. In the control group, the conventional health education was provided. In the observation group, on the base of the therapeutic regimen as the control group, the patients received the five-element music therapy to pacify the liver qi and strengthen the spleen functions, once every two days, 30 min each time, 3 treatments a week. The course of treatment consisted of 4 weeks. Before and after treatment, the TCM syndrome score and the MOS 36-item short form healthy survey (SF-36) score were compared between the two groups and the clinical therapeutic effect was evaluated. Using infrared thermal imaging, the temperature at the acupoints of the affected organs (liver, spleen), the related organs (gallbladder, stomach) and the other non-related zangfu organs (pericardium, lung) was detected before and after treatment in the two groups. RESULTS: After treatment, the TCM syndrome scores were reduced when compared with those before treatment in the two groups (P<0.01, P<0.05); the reduction in the observation group was larger than that of the control group (P<0.01). The score of each domain for the SF-36 in the observation group and the score of role-emotional domain in the control group were all increased when compared with the scores before treatment (P<0.01, P<0.05); and the score of each domain for the SF-36 in the observation group was higher than that in the control group (P<0.01). The total effective rate was 66.7% (20/30) in the observation group, which was higher than 10.0% in the control group (3/30, P<0.05). In the observation group, the temperature of the yuan-primary point, the back-shu point and the front-mu point related to the liver, as well as those related to the gallbladder after treatment was reduced when compared with the temperature before treatment; and the changes were larger than those of the control group (P<0.01). The temperature of the yuan-primary point, the back-shu point and the front-mu point related to the spleen, as well as the back-shu point and the front-mu point related to the stomach in the observation group was increased when compared with the temperature before treatment (P<0.01); and the changes were larger than those of the control group (P<0.01). For the temperature of the non-specific points related to the liver and spleen, as well as the yuan-primary point, the back-shu point and the front-mu point related to the pericardium and the lung, there was no significant differences when compared with the temperature at the above-mentioned acupoints before and after treatment (P>0.05). CONCLUSION TCM five-element music therapy associated with the conventional health education may effectively relieve the clinical symptoms and improve the quality of life in the patients with suboptimal health status of liver stagnation and sleep deficiency; and the therapeutic effect is better than the simple health education. The changes in the temperature of acupoints may reflect the functional regulation of the related zangfu organs in the body.
Humans ; Acupuncture Points ; Medicine, Chinese Traditional ; Spleen ; Music Therapy ; Quality of Life ; Temperature ; Liver ; Health Status

Objective: To learn the results of MNA ( mini nutritional assessment ） nutrition screening and influencing factors in the elderly living at home, so as to provide basis for improving the nutritional status of the elderly living at home. Methods: The elderly people at home were recruited from Yinzhou District, Yiwu City and Changshan County in Zhejiang Province by the multi-stage random sampling method. Their demographic information, living habits and nutritional status were collected by the MNA scale and the questionnaire for nutrition and health status surveillance. The multivariate linear regression model was used to analyze influencing factors for the nutritional status. Results: Of 374 study subjects, 186 ( 49.73% ) were males and 188 ( 50.27% ) were females. The age was ( 69.63±6.68 ) years ( range, 60-90 years ). The average score of MNA scale was 25.26±2.81. The prevalence of malnutrition risk in the elderly living at home was 20.59%. Age ( β'=-0.140), marital status ( β'=0.110 ), annual income ( β'=0.155 ), active physical exercise ( β'= 0.104 ), eating health products/nutritional supplements ( β'= 0.110 ) and satiety ( full diet β'=0.196 ) were influencing factors for MNA scores ( P<0.05 ）. Conclusion The prevalence of malnutrition risk among the elderly living at home is 20.59%. The prevalence increases with age. Having a spouse, doing active physical exercise, eating health products/nutritional supplements, having healthy eating habits are conducive to maintaining the nutritional health of the elderly.

Professor
Acupuncture ; Acupuncture Points ; Acupuncture Therapy ; Facial Paralysis/therapy* ; Humans ; Meridians ; Moxibustion

This study was aimed to develop a simple, rapid and reliable method for identifying Armeniacae Semen Amarum from different processed products and various rancidness degrees. The objective odor information of Armeniacae Semen Amarum was obtained by electronic nose. 105 batches of Armeniacae Semen Amarum samples were studied, including three processed products of Armeniacae Semen Amarum, fried Armeniacae Semen Amarum and peeled Armeniacae Semen Amarum, as well as the samples with various rancidness degrees: without rancidness, slight rancidness, and rancidness. The discriminant models of different processed products and rancidness degrees of Armeniacae Semen Amarum were established by Support Vector Machine(SVM), respectively, and the models were verified based on back estimation of blind samples. The results showed that there were differences in the characteristic response radar patterns of the sensor array of different processed products and the samples with different rancidness degrees. The initial identification rate was 95.90% and 92.45%, whilst validation recognition rate was 95.38% and 91.08% in SVM identification models. In conclusion, differentiation in odor of different processed and rancidness degree Armeniacae Semen Amarum was performed by the electronic nose technology, and different processed and rancidness degrees Armeniacae Semen Amarum were successfully discriminated by combining with SVM. This research provides ideas and methods for objective identification of odor of traditional Chinese medicine, conducive to the inheritance and development of traditional experience in odor identification.
Drugs, Chinese Herbal ; Electronic Nose ; Medicine, Chinese Traditional ; Semen ; Support Vector Machine

To discuss the effect of deterioration on the quality of Armeniacae Semen Amarum by observing the changes of macroscopic characteristics, active components and rancidness degrees of Armeniacae Semen Amarum in deterioration process. The traditional macroscopic identification was used to observe, identify and classify the morphologic and organleptic characteristics of Armeniacae Semen Amarum. The contents of amygdalin and fatty oil(two representatives of active components) were detected by HPLC and general rule 0713 in Chinese Pharmacopoeia, respectively. Acid value and peroxide value of the samples were selected as the representative indices of different rancidness degrees, and the general rule 2303 was adopted as the method for quantitative analysis. Then principal component analysis(PCA), partial least square analysis discrimination analysis(PLS-DA) were further utilized to establish the discriminative models of samples with different rancidness degrees, and also to screen out the largest contribution factors. In sensory evaluation, Armeniacae Semen Amarum samples were divided into three groups: non-rancid, slightly-rancid, and noticeably-rancid. The color of seed coat, cotyledon and surface of noticeably-rancid samples was deepened, and the odor differed much from non-rancid samples. Average content of amygdalin and fatty oil in non-rancid samples was 4.12% and 67.77%, respectively, both meeting the requirements of Chinese Pharmacopoeia; and decreased to some extent in slightly-rancid samples. However, the content of amygdalin sharply dropped to 0.074% in noticeably-rancid samples. The acid value and peroxide value were increased significantly with the intensifying of the rancidness degree, from only 1.363 and 0.016 74 in non-rancid samples to 1.865 and 0.023 70 in slightly-rancid samples, even doubled in noticeably-rancid samples(2.167 and 0.033 82). The discriminative models established by PCA and PLS-DA could complete the task of distinguishing the non-rancid samples from noticeably-rancid ones. The contribution degree of amygdalin content as one of the input attributes of discriminative model was higher than 1. Rancidness affected the quality of Armeniacae Semen Amarum, resulting in appearance changes, decrease in content of active components, and increase in acid value and peroxide value. Obviously, noticeably-rancid samples were non-conforming to Chinese Pharmacopoeia and no longer suitable for medicinal use. Rancidness can significantly reduce the quality of Armeniacae Semen Amarum, and even could possibly produce toxicity, which should attach more attention.
Amygdalin ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Semen

Objective To discuss the application of 3D laser scanner and computer technology in restoration of the accident scene and reconstruction of the accident process, as well as identification of the driver-passenger relationship. Methods The scene of a traffic accident, the accident vehicle and the vehicle of the same type as accident vehicle were scanned using 3D laser scanner. The accident scene, traces and accident vehicle were integrated using computer technology to restore the accident scene, and the accident process was reconstructed and analyzed by combining the characteristics of the body injuries. Results By restoring the accident scene and reconstructing the accident process with 3D laser scanner, it was determined that Wu was in the driving seat at the time of the accident. Conclusion It is more objective and scientific to use 3D laser scanning technology to restore the accident scene, reconstruct the accident process and analyze the moving track of the driver and passengers in the vehicle. It will help to improve the accuracy of forensic identification of road traffic accidents.
Accidents, Traffic ; Computer Simulation