Danlou Tablet Protects Against Myocardial Infarction Through Promoting eNOS-Dependent Endothelial Protection and Angiogenesis.

Myocardial infarction (MI) is one of the leading causes of death worldwide. Danlou tablet (Dan) is an effective traditional Chinese medicine for cardiac protection, although the underlying mechanism was not fully understood. In this study, we used a murine MI model and demonstrated that Dan administration effectively attenuated myocardial apoptosis, cardiac remodeling, and heart failure post MI. Dan increased CD31-positive capillaries in MI hearts, and reduced the apoptosis and oxidative stress in human umbilical vein endothelial cells after oxygen-glucose deprivation stress, simultaneously with the activated HIF-1α/VEGFA/eNOS signaling. Moreover, inhibition of eNOS by L-NAME attenuated Dan-induced protection against MI, and abolished its effect in promoting angiogenesis and reducing endothelial apoptosis and oxidative stress. Collectively, Dan is beneficial to promote eNOS-dependent endothelial protection and angiogenesis thus protecting against MI. A deep understanding of Dan-induced protection might help promote clinical usage of Dan in MI treatment.

Liquid metal microspheres with an eddy-thermal effect for magnetic hyperthermia-enhanced cancer embolization-immunotherapy.

Patients with hepatocellular carcinoma (HCC) display poor prognosis because HCC involves a high rate of metastasis and regrowth. Herein, we present an effective strategy to treat HCC using magnetic hyperthermia therapy (MHT)-enhanced cancer immunotherapy combined with transcatheter arterial embolization (TAE). Uniform liquid metal microspheres (LM MSs) obtained by microfluidic technology with powerful eddy-thermal effects could be used as both MHT and TAE agents for effective cancer therapy. The eddy-thermal effect of LM MSs demonstrated effective MHT, whereas LM MS-induced MHT boosted the immune system, promoted immune cell infiltration, and further stimulated powerful immune responses to suppress the growth of distant tumors, together with immune checkpoint blockade therapy. Furthermore, LM MS-lipiodol dispersion displayed excellent efficacy of the combined MHT-TAE in the orthotopic rabbit liver cancer model. Our work not only highlighted that LM MSs could act as effective MHT agents to achieve MHT-enhanced immunotherapy but also presented the significant promise of combining MHT with TAE for the efficient treatment of large orthotopic liver tumors.

Consensus co-expression network analysis identifies AdZAT5 regulating pectin degradation in ripening kiwifruit.

INTRODUCTION: Cell wall degradation and remodeling is the key factor causing fruit softening during ripening. OBJECTIVES: To explore the mechanism underlying postharvest cell wall metabolism, a transcriptome analysis method for more precious prediction on functional genes was needed. METHODS: Kiwifruits treated by ethylene (a conventional and effective phytohormone to accelerate climacteric fruit ripening and softening as kiwifruits) or air were taken as materials. Here, Consensus Coexpression Network Analysis (CCNA), a procedure evolved from Weighted Gene Co-expression Network Analysis (WGCNA) package in R, was applied and generated 85 consensus clusters from twelve transcriptome libraries. Advanced and comprehensive modifications were achieved by combination of CCNA and WGCNA with introduction of physiological traits, including firmness, cell wall materials, cellulose, hemicellulose, water soluble pectin, covalent binding pectin and ionic soluble pectin. RESULTS: As a result, six cell wall metabolisms related structural genes AdGAL1, AdMAN1, AdPL1, AdPL5, Adß-Gal5, AdPME1 and four transcription factors AdZAT5, AdDOF3, AdNAC083, AdMYBR4 were identified as hub candidate genes for pectin degradation. Dual-luciferase system and electrophoretic mobility shift assays validated that promoters of AdPL5 and Adß-Gal5 were recognized and trans-activated by transcription factor AdZAT5. The relatively higher enzyme activities of PL and ß-Gal were observed in ethylene treated kiwifruit, further emphasized the critical roles of these two pectin related genes for fruit softening. Moreover, stable transient overexpression AdZAT5 in kiwifruit significantly enhanced AdPL5 and Adß-Gal5 expression, which confirmed the in vivo regulations between transcription factor and pectin related genes. CONCLUSION: Thus, modification and application of CCNA would be powerful for the precious phishing the unknown regulators. It revealed that AdZAT5 is a key factor for pectin degradation by binding and regulating effector genes AdPL5 and Adß-Gal5.

Innovative ochre processing and tool use in China 40,000 years ago.

Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding1-4. Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown1,5-7. Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens, such as the Initial Upper Palaeolithic8-10. The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture2,3,6,11.

Effects of early vitamin D supplementation on the prevention of bronchopulmonary dysplasia in preterm infants.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a respiratory dysfunction caused by poor lung bronchial development, which may lead to long-term lung disease, threatening the lives of children. Studies have shown that premature infants with low vitamin D are highly associated with BPD. In this study, we aim to obtain insights into whether early vitamin D supplementation could prevent BPD in preterm infants. METHODS: A total of 112 preterm infants were randomly divided into two groups: the control and vitamin D supplementation (VD) group. The VD group received vitamin D (800 IU/day) within 48 h at birth for consecutively 28 days. The serum levels of 25(OH)D3 and C-reactive protein (CRP), IL6, and TNF-α were measured using ELISA assay. The arterial partial pressure of oxygen (PaO2 ) and carbon dioxide (PaCO2 ) was measured using an i-STAT analyzer. RESULTS: The occurrence of BPD was decreased in the VD group compared with the control. The decreased serum 25(OH)D3 was significantly elevated by supplementation with vitamin D. In addition, the serum inflammation factors (CRP, IL6, and TNF-α) were significantly reduced by vitamin D supplementation. CONCLUSION: We demonstrated that early vitamin D supplementation could significantly reduce BPD incidence in preterm infants. We showed that early vitamin D supplementation could significantly increase serum level of 25(OH)D3 and reduce inflammatory response thereby preventing and reducing neonatal BPD. LIMITATION: Firstly, a larger sample size will be needed to be included to gain a comprehensive understanding of the protective effects of vitamin D and BPD mechanistically in preterm infants. Secondly, the pathophysiological process of BPD will need to be studied. In addition, the pathways that vitamin D is responsible for, need to be further researched.

O-glycosyltransferases from Homo sapiens contributes to the biosynthesis of Glycyrrhetic Acid 3-O-mono-ß-D-glucuronide and Glycyrrhizin in Saccharomyces cerevisiae.

Glycyrrhizin (GL) and Glycyrrhetic Acid 3-O-mono-ß-D-glucuronide (GAMG) are the typical triterpenoid glycosides found in the root of licorice, a popular medicinal plant that exhibits diverse physiological effects and pharmacological manifestations. However, only few reports are available on the glycosylation enzymes involved in the biosynthesis of these valuable compounds with low conversion yield so far. In mammals, glycosyltransferases are involved in the phase II metabolism and may provide new solutions for us to engineer microbial strains to produce high valued compounds due to the substrate promiscuity of these glycosyltransferases. In this study, we mined the genomic databases of mammals and evaluated 22 candidate genes of O-glycosyltransferases by analyzing their catalytic potential for O-glycosylation of the native substrate, glycyrrhetinic acid (GA) for its glycodiversification. Out of 22 selected glycosyltransferases, only UGT1A1 exhibited high catalytic performance for biosynthesis of the key licorice compounds GL and GAMG. Molecular docking results proposed that the enzymatic activity of UGT1A1 was likely owing to the stable hydrogen bonding interactions and favorite conformations between the amino acid residues around substrate channels (P82~R85) and substrates. Furthermore, the complete biosynthesis pathway of GL was reconstructed in Saccharomyces cerevisiae for the first time, resulting in the production of 5.98 ± 0.47 mg/L and 2.31 ± 0.21 mg/L of GL and GAMG, respectively.

Mechanisms exploration of Angelicae Sinensis Radix and Ligusticum Chuanxiong Rhizoma herb-pair for liver fibrosis prevention based on network pharmacology and experimental pharmacologylogy.

Angelicae Sinensis Radix (Danggui) and Ligusticum Chuanxiong Rhizoma (Chuan Xiong) herb-pair (DC) have been frequently used in Traditional Chinese medicine (TCM) prescriptions for hundreds of years to prevent vascular diseases and alleviate pain. However, the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear. In the present study, the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model. Based on the network pharmacological analysis of 13 bioactive ingredients found in DC, a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained, which was associated with mitogen-activated protein kinase (MAPK) signal pathway, hepatic inflammation and fibrotic response. Furthermore, this hypothesis was verified using carbon tetrachloride (CCl4)-induced fibrosis model. Measurement of liver functional enzyme activities and histopathological examination showed that DC dramatically reduced bile acid levels, inflammatory cell infiltration and collagen deposition caused by CCl4. The increased expression of liver fibrosis markers, such as collagen 1, fibronectin, α-smooth muscle actin (α-SMA) and transforming growth factor-ß (TGF-ß), and inflammatory factors, such as chemokine (C-C motif) ligand 2 (MCP-1), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and IL-6 in fibrotic mice were significantly downregulated by DC herb-pair through regulation of extracellular signal-regulated kinase 1/2 (ERK1/2)-protein kinase B (AKT) signaling pathways. Collectively, these results suggest that DC prevents the development of liver fibrosis by inhibiting collagen deposition, decreasing inflammatory reactions and bile acid accumulation, which provides insights into the mechanisms of herb-pair in improving liver fibrosis.

Tea Polyphenol Attenuates Oxidative Stress-Induced Degeneration of Intervertebral Discs by Regulating the Keap1/Nrf2/ARE Pathway.

OBJECTIVE: Intervertebral disc degeneration (IDD) and low back pain caused by IDD have attracted public attention owing to their extremely high incidence and disability rate. Oxidative stress is a major cause of IDD. Tea polyphenols (TP) are natural-derived antioxidants extracted from tea leaves. This study explored the protective role of TP on the nucleus pulposus cells (NPCs) of intervertebral discs and their underlying mechanism. METHODS: An in vitro model of H2O2-induced degeneration of NPCs was established. RT-qPCR and western blotting were used to detect the mRNA and protein expression of the targets. An in vivo model of IDD was established via acupuncture of the intervertebral disc. Radiological imaging and histological staining were performed to evaluate the protective role of TP. RESULTS: H2O2 contributed to NPC degeneration by inducing high levels of oxidative stress. TP treatment effectively increased the expression of nucleus pulposus matrix-associated genes and reduced the expression of degeneration factors. Further mechanistic studies showed that TP delayed H2O2-mediated NPC degeneration by activating the Keap1/Nrf2/ARE pathway. In vivo experiments showed that TP delayed the degeneration of NPCs in rats through the Keap1/Nrf2/ARE pathway. CONCLUSION: Our study confirmed that TP activates the Keap1/Nrf2/ARE pathway to exert an antioxidative stress role, ultimately delaying the degeneration of intervertebral discs.

Effect of Rhythm of Music Therapy on Gait in Patients with Stroke.

AIM: This study aims to analyze the effects of rhythm of music therapy on gait in patients with ischemic stroke, and explore the value of music therapy in walking training in stroke. METHODS: The present study is a prospective clinical study. Sixty patients with ischemic stroke, who were admitted to our hospital from October 2017 to December 2018, were enrolled. These patients were divided into two groups, according to the method of the random number table, with thirty patients in each group: control group and study group. Patients in the control group received conventional drug therapy, rehabilitation training and walking training, while the patients in the study group were given music therapy on the basis of the above mentioned therapies for four weeks, during which Sunday was regarded as a rest day, and the music therapy was suspended. The main outcome measures included indexes in evaluating the walking ability of patients in these two groups. At each time point, the Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS) and stroke rehabilitation treatment satisfaction questionnaire were used. RESULTS: The results revealed that the stride length, cadence and maximum velocity were higher in patients in the study group, when compared to patients in the control group, at the second week and end of the therapy, and the difference in step length between the affected side and healthy side was significantly lower in the study group than in the control group. These differences were statistically significant (P < 0.05). In the second week of therapy and at the end of therapy, the FMA and BBS scores were higher in the study group than in the control group, and the difference was statistically significant (P < 0.05). The total satisfaction rate was higher in the study group than in the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Under the stimulation of music rhythm, applying music therapy to patients with ischemic stroke can improve their gait, walking ability, lower limb motor function, balance ability and treatment satisfaction.

Efficacy and safety of Shexiang Baoxin pill (MUSKARDIA) in patients with stable coronary artery disease: a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial.

BACKGROUND: The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD. METHODS: A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency. RESULTS: In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio = 0.80; 95% confidence interval: 0.45-1.07; P  = 0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P = 0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P = 0.8785). CONCLUSIONS: As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD. TRIAL REGISTRATION: chictr.org.cn, No. ChiCTR-TRC-12003513.

[Analysis of theoretical basis and clinical application of dog-days moxibustion].

The present situation of the clinical application of dog-days moxibustion (moxibustion applied in the three periods of the hot season) is summarized so as to provide the guide for the theoretic study and clinical application of dog-days moxibustion. The intervention time of dog-days moxibustion is on the 1st day of each of the three periods of the hot season. Simultaneously, the geographic factors are considered. The disorders of lung system are mostly dominant among the indications of dog-days moxibustion, complicated with spleen and stomach disorders as well as cold and deficiency syndromes/patterns. The acupoints are mainly selected from the front-mu points on the chest and the back-shu points on the back, in combination with the differentiation of diseases, symptoms/patterns and the disorder stages. The duration of treatment is ranged from 1 to 3 years. The clinical therapeutic effect is improved constantly along with the increase of treatment periods by years.

Seasonal Zinc Storage and a Strategy for Its Use in Buds of Fruit Trees.

Bud dormancy allows deciduous perennial plants to rapidly grow following seasonal cold conditions. Although many studies have examined the hormonal regulation of bud growth, the role of nutrients remains unclear. Insufficient accumulation of the key micronutrient zinc (Zn) in dormant buds affects the vegetative and reproductive growth of perennial plants during the subsequent year, requiring the application of Zn fertilizers in orchard management to avoid growth defects in fruit trees. However, the mechanisms of seasonal Zn homeostasis in perennial plants remain poorly understood. Here, we provide new insights into Zn distribution and speciation within reproductive and vegetative buds of apple (Malus domestica) and four other deciduous fruit trees (peach [Amygdalus persica], grape [Vitis vinifera], pistachio [Pistacia vera], and blueberry [Vaccinium spp.]) using microscopic and spectroscopic characterization techniques comprising synchrotron-based x-ray fluorescence and x-ray absorption near-edge-structure analyses. By establishing a link between bud development and Zn distribution, we identified the following important steps of Zn storage and use in deciduous plants: Zn is preferentially deposited in the stem nodes subtending apical and axillary buds; Zn may then be sequestered as Zn-phytate prior to dormancy; in spring, Zn effectively releases for use during budbreak and subsequent meristematic growth. The mechanisms of Zn homeostasis during the seasonal cycles of plant growth and dormancy described here will contribute to improving orchard management, and to selection and breeding of deciduous perennial species.

Clinical Practice Guideline of Integrative Chinese and Western Medicine for Acute Myocardial Infarction.

With increasing morbidity and mortality, acute myocardial infarction (AMI) has become one of the major causes of human death, leading to heavy burdens to individuals, families and society. Previous researches have found that though large amount of resources and great effort were devoted, no significant improvements were achieved in reducing the in-hospital mortality of AMI patients. Meanwhile, extensive studies about Chinese medicine (CM) have found that CM has special advantages in treating AMI patients. However, there is no standardized and unified clinical practice guideline (CPG) of CM for AMI. Therefore, a CPG with strict standard and generally acknowledgement is urgent to be established. This guideline was developed following the methodological process established by the World Health Organization Handbook for Guideline Development. Extensive search on clinical evidences including systematic review (SR), randomized controlled trial (RCT), observational study and case reports was launched, covering evidence of CM for AMI on several aspects, such as diagnosis, CM patterns, CM interventions on AMI and complications, cardiac rehabilitation and clinical pathway management. Besides, the application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach enabled the evaluation of evidence and formulation of grade of recommendation (GOR) and level of evidence (LOE). With the help of GOR and LOE, this CPG recommends the integrative CM and WM treatment method in AMI patients and provides useful information on medical decision for clinical physicians.

Effect of integrated control intervention on soil-transmitted helminth infections in Jiangxi province in southeast China.

Soil transmitted helminths (STHs) burden was enormous in China several decades ago, however, rigorous control efforts have been successful with appreciable reduction in diseases burden. Here, we assessed provincial-level data derived from cross sectional surveys, executed in 1989, 2002 and 2014, on the prevalence of STHs among populations in Jiangxi province, China. This study, also, reported STHs integrated control intervention aimed at reducing STHs transmission and worm burden among population at county-level. The intervention strategies included mass drug administration (MDA), health education, improved water supply for drinking, improved sanitary facilities and environmental modification in Guixi municipality. The overall infection rate of STHs in Jiangxi province decreased from 77.7% (1989) to 6.3% (2014), while Ascaris lumbricoides, hookworm and Trichuris trichiura decreased from 71.1%, 17.6% and 17.0% (1989) to 0.9%, 4.7% and 1.0% (2014), respectively. STHs infection rates in female population were higher than male in the three surveys. Reduction in STHs prevalence was observed in all age groups, but the decline was less in higher age group. STHs prevalence in Guixi intervention region indicated remarkable reduction from 31.8% (2006) to 6.1% (2009) (χ2＝255.22, P＜0.01). A. lumbricoides, hookworm and T. trichiura infection rates decreased from 10.4%, 17.0% and 7.1% (2006) to 0.1%, 4.1% and 2.2%, respectively (2009) (X2A.l = 110.23, P<0.01; X2hk = 103.57, P < 0.01; X2T.t = 32.0, P < 0.01). A. lumbricoides infection rate declined the most of all STHs. Following control efforts with integrated control intervention strategies, STHs prevalence in Jiangxi province experienced remarkable trend in decline between 1989 and 2014. Consolidating control efforts with sustained integrated control strategies is, therefore, important to achieving STHs elimination in China.

[Effects of herbal-cake-separated moxibustion on the repair of vascular endothelial and SDF-1 in rabbits with atherosclerosis].

OBJECTIVE: To observe the effects of herbal-cake-separated moxibustion on the repair of damaged vascular endothelium structure and the content of stromal cells derived factor 1 (SDF-1) in rabbits with atherosclerosis. METHODS: A total of 75 rabbits were randomly divided into a normal group, a model group, a direct moxibustion group, an atorvastatin calcium group and a herbal-cake-separated moxibustion group, 15 rabbits in each one. The rabbits in the normal group were fed with normal diet, and the remaining rabbits were fed with high-cholesterol diet for 12 weeks to prepare atherosclerotic model. Two groups of acupoints, one was "Juque" (CV 14), "Tianshu" (ST 25) and "Fenglong" (ST 40), the other one was "Xinshu" (BL 15), "Ganshu" (BL 18) and "Pishu" (BL 20), were applied in the direct moxibustion group and herbal-cake-separated moxibustion group; the two groups of acupoints were selected alternatively every other day. The moxibustion was given for 30 min per treatment, once a day for 4 weeks. The rabbits in the atorvastatin calcium group were treated with atorvastatin calcium tablets (1.96 mg•kg-1•d-1) which were crushed into powder and mixed into breakfast. After modeling, the rabbits in the normal group and model group received no treatment, and immobilized at the time when moxibustion was applied in other three groups. The levels of total cholesterol (TC) and triglyceride (TG) were measured by enzymic method; the low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by colorimetric method; the morphological structure of aortic wall was observed under optical microscope; the serum level of SDF-1 was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: After treatment, compared with the normal group, the levels of TC, TG and LDL-C were significantly increased in the model group (all P<0.01), and the level of HDL-C was decreased (P<0.01). Compared with the model group, the levels of TC, TG and LDL-C were significantly decreased (all P<0.01), and the level of HDL-C was significantly increased in the direct moxibustion group, atorvastatin calcium group and herbal-cake-separated moxibustion group (P<0.01, P<0.05). Compared with the normal group, the morphological structure of aortic wall was significantly damaged in the model group. Compared with the model group, the vascular endothelial structure was improved in the atorvastatin calcium group and herbal-cake-separated moxibustion group, and the pathological change of aorta endothelial in the direct moxibustion group was relieved. After treatment, compared with the model group, the level of SDF-1 was increased in the direct moxibustion group, atorvastatin calcium group and herbal-cake-separated moxibustion group (P<0.05, P<0.01); the level of SDF-1 in the herbal-cake- separated moxibustion group was higher than that in the direct moxibustion group (P<0.05). CONCLUSION: The herbal- cake-separated moxibustion can promote the expression of SDF-1 in serum and repair the damaged aortic endothelial structure.

Observational Study of Chinese Medicine Syndrome Distribution in Patients with Acute Myocardial Infarction and Its Impact on Prognosis.

OBJECTIVE: To investigate the distribution of Chinese medicine (CM) syndrome in patients with acute myocardial infarction (AMI) on admission and its impact on prognosis. METHODS: A total of 525 AMI patients were prospectively recruited and classifified into 4 groups based on their clinical characteristics: excess-heat, excess-cold, deficiency-heat and deficiency-cold syndromes. Major adverse cardiovascular events (MACEs) were followed up. RESULTS: The excess syndrome was more common than deficiency syndrome (72.95% vs. 27.05%; P<0.05). Totally 495 (94.29%) of 525 AMI patients were followed up (median 277 days). There were 59 (11.92%) MACEs. After adjusted with confounding factors in Cox regression models, the hazard ratio (95% confifidence interval) of excess-heat, excess-cold, defificiency-heat and defificiency-cold syndrome groups were 1, 1.25 (0.63, 2.49; P<0.05), 2.37 (1.14, 4.94; P<0.05), 3.76 (1.71, 8.28; P<0.05), respectively. CONCLUSIONS: Excess syndrome was more common in AMI patients and had better prognosis, while defificiency-cold syndrome had the poorest prognosis. CM syndrome was of value in predicting long-term outcomes in AMI patients.

Clinical practice guideline of integrative Chinese and Western medicine for acute myocardial infarction

With increasing morbidity and mortality, acute myocardial infarction (AMI) has become one of the major causes of human death, leading to heavy burdens to individuals, families and society. Previous researches have found that though large amount of resources and great effort were devoted, no significant improvements were achieved in reducing the in-hospital mortality of AMI patients. Meanwhile, extensive studies about Chinese medicine (CM) have found that CM has special advantages in treating AMI patients. However, there is no standardized and unified clinical practice guideline (CPG) of CM for AMI. Therefore, a CPG with strict standard and generally acknowledgement is urgent to be established. This guideline was developed following the methodological process established by the World Health Organization Handbook for Guideline Development. Extensive search on clinical evidences including systematic review (SR), randomized controlled trial (RCT), observational study and case reports was launched, covering evidence of CM for AMI on several aspects, such as diagnosis, CM patterns, CM interventions on AMI and complications, cardiac rehabilitation and clinical pathway management. Besides, the application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach enabled the evaluation of evidence and formulation of grade of recommendation (GOR) and level of evidence (LOE). With the help of GOR and LOE, this CPG recommends the integrative CM and WM treatment method in AMI patients and provides useful information on medical decision for clinical physicians.

A novel therapeutic vaccine composed of a rearranged human papillomavirus type 16 E6/E7 fusion protein and Fms-like tyrosine kinase-3 ligand induces CD8+ T cell responses and antitumor effect.

The development of cervical cancer is mainly caused by infection with high risk genotypes of human papillomavirus, particularly type 16 (HPV16), which accounts for more than 50% of cervical cancer. The two early viral oncogenes, E6 and E7, are continuously expressed in cervical cancer cells and are necessary to maintain the malignant cellular phenotype, thus providing ideal targets for immunotherapy of cervical cancer. In this study, a novel vaccine strategy was developed based on a rationally shuffled HPV16 E6/E7 fusion protein, the addition of Fms-like tyrosine kinase-3 ligand (Flt3L) or the N domain of calreticulin (NCRT), and the usage of a CpG adjuvant. Four recombinant proteins were constructed: m16E6E7 (mutant E6/E7 fusion protein), rm16E6E7 (rearranged mutant HPV16 E6/E7 fusion protein), Flt3L-RM16 (Flt3L fused to rm16E6E7), and NCRT-RM16 (NCRT fused to rm16E6E7). Our results suggest that Flt3L-RM16 was the most potent of these proteins in terms of inducing E6- and E7-specific CD8+ T cell responses. Additionally, Flt3L-RM16 significantly induced regression of established E6/E7-expressing TC-1 tumors. Higher doses of Flt3L-RM16 trended toward higher levels of antitumor activity, but these differences did not reach statistical significance. In summary, this study found that Flt3L-RM16 fusion protein is a promising therapeutic vaccine for immunotherapy of HPV16-associated cervical cancer.

Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial.

Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events. Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration: clinicaltrials.gov Identifier: NCT01573858.

Circadian Rhythm Influences the Promoting Role of Pulsed Electromagnetic Fields on Sciatic Nerve Regeneration in Rats.

Circadian rhythm (CR) plays a critical role in the treatment of several diseases. However, the role of CR in the treatment of peripheral nerve defects has not been studied. It is also known that the pulsed electromagnetic fields (PEMF) can provide a beneficial microenvironment to quicken the process of nerve regeneration and to enhance the quality of reconstruction. In this study, we evaluate the impact of CR on the promoting effect of PEMF on peripheral nerve regeneration in rats. We used the self-made "collagen-chitosan" nerve conduits to bridge the 15-mm nerve gaps in Sprague-Dawley rats. Our results show that PEMF stimulation at daytime (DPEMF) has most effective outcome on nerve regeneration and rats with DPEMF treatment achieve quickly functional recovery after 12 weeks. These findings indicate that CR is an important factor that determines the promoting effect of PEMF on peripheral nerve regeneration. PEMF exposure in the daytime enhances the functional recovery of rats. Our study provides a helpful guideline for the effective use of PEMF mediations experimentally and clinically.