Role and mechanism of the p-JAK2/p-STAT3 signaling pathway in follicular development in PCOS rats.

OBJECTIVE: To identify the association between the phosphorylated Janus kinase 2/phosphorylated signal transducer and activator of transcription (p-JAK2/p-STAT3) signaling pathway and follicular development in polycystic ovary syndrome (PCOS) rats, and explore the underlying mechanism. To evaluate the role of exogenous JAK2 inhibitor AG490 in the model and the associations among luteinizing hormone/choriogonadotropin receptor (LHCGR), follicle-stimulating hormone receptor (FSHR), cytochrome P450 17α (CYP17a), cytochrome P450 19 (CYP19), and PCOS. RESULTS: Rat models of PCOS was established. PCOS rats were intraperitoneally treated with double-distilled water (ddH2O)/DMSO/AG490. The rate of ovarian morphological recovery in the AG490 group was significantly higher compared with the DMSO group (83.3 % vs 9.1 %, X2 = 12.68, P < 0.001). Moreover, the short in the time the estrous cycle was resumed in the AG490 group (hazard ratio = 16.32, P < 0.001) compared with the DMSO group. Compared with the controls, p-JAK2, p-STAT3, LHCGR, and CYP17a expression levels were increased whereas that of FSHR and CYP19 were decreased in the ovaries of PCOS rats. However, an opposite trend was observed after treatment with AG490. Software prediction revealed that the p-STAT3 bound to the promoter regions of LHCGR, FSHR, CYP17a, and CYP19 genes. This finding was confirmed by results of correlation analysis (R = 0.834, -0.836, 0.875 and -0.712, respectively, all P < 0.001). CONCLUSION: This study demonstrated that the p-JAK2/p-STAT3 signaling pathway was involved in follicular development in PCOS rats by upregulating LHCGR and CYP17a expression, and downregulating that of FSHR and CYP19. AG490 treatment exerted beneficial effects. LHCGR, FSHR, CYP17a, and CYP19 are candidate genes associated with follicular development in PCOS rats.

CiteSpace knowledge map of gut microbiota research involving traditional Chinese medicine in recent twenty years / 中国中药杂志

We employed bibliometrics to comprehensively study the hotspots and frontiers of gut microbiota research involving traditional Chinese medicine(TCM), aiming to provide new ideas for the subsequent research in this field. The studies of gut microbiota with TCM published from January 1, 2002 to December 31, 2021 were retrieved from CNKI, Wanfang, VIP and Web of Science(WoS). After data screening and cleaning, CiteSpace 5.8.R3 was used to visualize and analyze the authors, journals, and keywords. A total of 1 119 Chinese articles and 815 English articles were included in the study. The period of 2019-2021 witnessed the surge in the number of articles published in this field, being the peak research period. TAN Zhou-jin and DUAN Jin-ao were the authors publishing the most articles in Chinese and English, respectively. The two authors ranked top in both Chinese and English articles, playing a central role in this research field. The top five Chinese and English journals in this field had a large influence in the international research field. High-frequency keywords and keyword clustering showed that the research hotspots in this field were concentrated in four areas: trial and clinical research on the regulation of gut microbiota in disease treatment by TCM, metabolic transformation of Chinese medicines by gut microbiota, and the effect of TCM added to feed on the gut microbiota and growth performance of animals. The study of gut microbiota structure in patients with different TCM syndromes, as well as that of TCM combined with probiotics/flora transplantation in the treatment of diseases, can provide new ideas for clinical diagnosis and traditional drug treatment of diseases and has great research space and research value in the future.

Effect of Zuogui Jiangtang Tongmai Prescription on SCFAs/GPR43/GLP-1/GLP-1R Signaling Pathway in Rats with Diabetes Mellitus Complicated with Cerebral Infarction / 中国实验方剂学杂志

ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Tongmai prescription （ZJT） in the treatment of diabetes mellitus complicated with cerebral infarction （DM-CI） in rats based on the short-chain fatty acids （SCFAs）/G protein-coupled receptor 43 （GPR43）/glucagon-like peptide-1 （GLP-1）/GLP-1 receptor （GLP-1R） signaling pathway. MethodSixty SD rats were randomly divided into sham operation group， model group， low- and high-dose ZJT groups （12， 24 g·kg-1）， western medicine group （140 mg·kg-1 pioglitazone metformin tablets + 27 mg·kg-1 enteric-coated aspirin tablets）. Except for the sham operation group， all other groups were fed a high-sugar high-fat diet for 4 weeks and then subjected to intraperitoneal injection of 1% streptozotocin at 35 mg·kg-1 combined with middle cerebral artery occlusion （MCAO） to establish a DM-CI rat model. The corresponding interventions were performed with distilled water， low-dose ZJT， high-dose ZJT， pioglitazone metformin tablets， and enteric-coated aspirin tablets. After surgery， National Institutes of Health Stroke Scale （NIHSS） scoring and triphenyltetrazolium chloride （TTC） staining to measure the rat's cerebral infarct volume were carried out. Random blood glucose levels were measured， and hematoxylin-eosin （HE） staining was used to observe histopathological changes in rat brain tissues. Gas chromatography was employed to detect the content of SCFAs in the cecum contents. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure serum GLP-1 level. Western blot was used to detect the protein expression of GPR43 in rat ileal tissues and GLP-1R in the ischemic brain tissues. ResultCompared with the sham operation group， the model group showed significantly increased NIHSS scores， random blood glucose levels， and cerebral infarct volumes （P<0.01）， and significantly decreased SCFAs content， GLP-1 levels， and GPR43 and GLP-1R protein expression （P<0.01）. Compared with the model group， the high-dose ZJT group and the western medicine group exhibited significantly reduced NIHSS scores， random blood glucose levels， and cerebral infarct volumes （P<0.05， P<0.01）， and significantly increased SCFAs content， GLP-1 levels， and GPR43 and GLP-1R protein expression （P<0.01）. ConclusionZJT can improve glucose metabolism disorder and reduce neurological damage in DM-CI rats， and its mechanism may be related to the increase in SCFAs content and the upregulation of the GPR43/GLP-1/GLP-1R signaling pathway.

Experimental study on the improvement of inflammatory response in rats with cerebral ischemia by Chinese ultrasound drug permeation electrotherapy device / 国际中医中药杂志

Objective:To observe the effects of Traditional Chinese Medicine (TCM)ultrasound drug permeation electrotherapy device on the inflammatory response of rats with cerebral ischemia, and to provide an experimental basis for the clinical application of TCM ultrasound drug permeation electrotherapy device in the treatment of cerebral ischemia.Methods:A total of 72 SD rats were randomly divided into sham-operation group (12 rats) and modeling group (60 rats). The middle cerebral artery occlusion (MCAO) model was prepared by thread embolism in the model group. The rats were divided into model group, Chinese medicine tablet group, blank tablet + TCM ultrasound drug permeation electrotherapy group (hereinafter referred to as "blank tablet + electrotherapy group"), Chinese medicine tablet + TCM ultrasound drug permeation electrotherapy group (hereinafter referred to as "Chinese medicine tablet + electrotherapy group") and butylphthalide group according to the random number table method, with 12 rats in each group. The corresponding treatment was given continuously for 7 days. The neurological function was scored using Longa method evaluation criteria; TTC staining was used to observe the infarct volume and calculate the percentage of infarct volume; HE staining was used to observe the cell morphology of cortical area in each group of rats; ELISA was used to detect the serum TNF-α and IL-1β levels in each group of rats; TLR4, MyD88 and NF-κBp65 protein expressions in hippocampal tissue of each group of rats on the infarct side were detected by Western blot method.Results:Compared with the model group, the neurological function scores of rats in the blank tablet + electrotherapy group, the herbal tablet + electrotherapy group, and the butylphthalein group significantly decreased ( P<0.05), the percentage of cerebral infarct volume significantly decreased ( P<0.05), the contents of serum TNF-α and IL-1β significantly decreased ( P<0.05), and the expressions of TLR4 (0.42±0.07, 0.31±0.07, 0.19±0.04 vs. 0.68±0.14), MyD88 (0.39±0.12, 0.30±0.07, 0.23±0.11 vs. 0.67±0.10), NF-κBp65 (0.32±0.03, 0.27±0.02, 0.17±0.03 vs. 0.57±0.12) protein in hippocampal tissue significantly decreased ( P<0.05). Conclusion:The TCM ultrasound drug permeation electrotherapy device can inhibit TLR4, MyD88, NF-κBp65 protein expressions and reduce the release of serum inflammatory factors TNF-α and IL-1β, thus exerting cerebral ischemic protective effects.

Evaluation of Myocardial Perfusion Classification for Interventional Treatment of Chronic Total Occlusion of Coronary Artery / 中山大学学报(医学科学版)

【Subjects】 To investigate the clinical application value of myocardial contrast echocardiography （MCE） in selecting CTO-PCI patients. MethodsFrom February 2019 to March 2020， a total of 50 patients with chronic coronary artery occlusion were consecutively selected as the research subjects. MCE and two-dimensional speck-tracking echocardiography were completed before and 12 months after interventional therapy. The primary end point was major adverse cardiovascular events. Patients were divided into groups according to the preoperative myocardial perfusion level of MCE. The improvement of left ventricular function was evaluated by two-dimensional echocardiography and left ventricular global longitudinal strain. ResultsCompared with the abnormal perfusion group， the improvement of GLS in the normal perfusion group was greater （P=0.028）. The wall motion score index （WMSI） of the abnormal perfusion group before PCI was higher than that of the normal perfusion group （P=0.002）. WMSI in the abnormal perfusion group was higher than that in the normal perfusion group one year after PCI （P<0.001）. The left ventricular GLS（P=0.008）.WMSI（P=0.016） and left ventricular end-diastolic volume（P=0.032） in the normal perfusion group were improved compared with those before operation； The postoperative perfusion score of patients with abnormal perfusion was significantly improved （ P=0.032）. ConclusionMCE has clinical application value in optimizing the selection of CTO-PCI patients. CTO patients with different myocardial perfusion types have different benefits after PCI.

Mechanism of Xumingtang in Gu Jin Lu Yan for Treatment of Ischemic Stroke Based on HIF-1α/NLRP3 Pathway-mediated Pyroptosis / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Xumingtang in Gu Jin Lu Yan （《古今录验》） in regulating cell pyroptosis through the hypoxia-inducible factor-1α （HIF-1α）/NOD-like receptor pyrin domain-containing protein 3 （NLRP3） pathway in ischemic stroke （IS）. MethodSD rats were randomly divided into a sham operation group， a model group， low- and high-dose Xumingtang groups， and a metformin group， with 20 rats in each group. Oral administration was performed for 3 days， and tissue samples were collected. Differential messenger RNA （mRNA） was screened using high-throughput sequencing， and Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analyses were performed on key differentially expressed genes. The modified neurological severity score （mNSS） and 2，3，5-triphenyltetrazolium chloride （TTC） staining were used to evaluate the effect of brain infarction. Hematoxylin-eosin （HE） staining was used for pathological morphological observation of brain tissue. Enzyme-linked immunosorbent assay （ELISA） was used to compare the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in the ischemic cortical region. Double staining immunohistochemistry was used to detect the co-localization of HIF-1α and NLRP3. Real-time quantitative polymerase chain reaction （PCR） was performed to detect the mRNA expression of NLRP3， HIF-1α， Caspase-1 （CASP-1）， and gasdermin D （GSDMD）. Western blot was used to detect the protein expression of HIF-1α， NLRP3， CASP-1， and GSDMD. ResultA total of 5 705 differentially expressed genes （2 733 downregulated and 2 972 upregulated） were obtained by mRNA sequencing. After conversion to homologous genes and intersection with the pyroptosis gene set， 95 key differentially expressed pyroptosis genes were obtained. Compared with the sham operation group， the model group showed significantly increased mNSS scores， larger brain infarction areas （P<0.01）， diverse neuronal morphology， disordered arrangement， widened cell gaps， significantly increased levels of IL-1β and IL-18 in the ischemic cortical region （P<0.01）， enhanced co-localization fluorescence intensity， and significantly increased mRNA and protein expression levels of HIF-1α， NLRP3， CASP-1， and GSDMD （P<0.01）. Compared with the model group， the high-dose Xumingtang group showed the most significant improvement in neurological function scores and brain infarction areas （P<0.01）. The neuronal integrity and arrangement were more complete， and the cell gaps were narrower in all groups with drug treatment， with significantly reduced co-localization fluorescence intensity. Xumingtang could reduce the levels of IL-1β， IL-18， and the mRNA and protein expression of HIF-1α， NLRP3， CASP-1， and GSDMD （P<0.05， P<0.01）， with the high-dose Xumingtang group showing the most significant effect （P<0.01）. ConclusionXumingtang in Gu Jin Lu Yan can inhibit cell pyroptosis and promote neurological function recovery after IS， which may be related to the inhibition of the HIF-1α/NLRP3 pathway.

Curcumin Alleviates Hyperandrogenism and Promotes Follicular Proliferation in Polycystic Ovary Syndrome Rats: Insights on IRS1/PI3K/GLUT4 and PTEN Modulations.

OBJECTIVE: To explore the effect of curcumin on the insulin receptor substrate 1 (IRS1)/phosphatidylinositol-3-kinase (PI3K)/endometrial expression of glucose 4 (GLUT4) signalling pathway and its regulator, phosphatase and tensin homolog (PTEN), in a rat model of polycystic ovarian syndrome (PCOS). METHODS: PCOS model was induced by letrozole intragastric administration. Sprague-Dawley rats were randomized into 4 groups according to a random number table: (1) control group; (2) PCOS group, which was subjected to PCOS and received vehicle; (3) curcumin group, which was subjected to PCOS and treated with curcumin (200 mg/kg for 2 weeks); and (4) curcumin+LY294002 group, which was subjected to PCOS, and treated with curcumin and LY294002 (a specific PI3K inhibitor). Serum hormone levels (17 ß-estradiol, follicle stimulating hormone, luteinizing hormone, progesterone, and testosterone) were measured by enzyme linked immunosorbent assay, and insulin resistance (IR) was assessed using the homeostasis model assessment of IR. Ovarian tissues were stained with haematoxylin and eosin for pathological and apoptosis examination. Expression levels of key transcriptional regulators and downstream targets, including IRS1, PI3K, protein kinase B (AKT), GLUT4, and PTEN, were measured via reverse transcription polymerase chain reaction and Western blot, respectively. RESULTS: The PCOS group showed impaired ovarian morphology and function. Compared with the PCOS group, curcumin treatment exerted ovarioprotective effects, down-regulated serum testosterone, restored IR, inhibited inflammatory cell infiltration in ovarian tissues, decreased IRS1, PI3K, and AKT expressions, and up-regulated GLUT4 and PTEN expressions in PCOS rats (P<0.05 or P<0.01). In contrast, IRS1, PI3K, AKT, and PTEN expression levels were not significantly different between PCOS and curcumin+LY294002 groups (P>0.05). CONCLUSION: The beneficial effects of curcumin on PCOS rats included the alteration of serum hormone levels and recovery of morphological ovarian lesions, in which, PTEN, a new target, may play a role in regulating the IRS1/PI3K/GLUT4 pathway.

Relationship Between NLRP3 Inflammasome and Ischemic Stroke and Intervention Effect of Traditional Chinese Medicine / 中国实验方剂学杂志

Ischemic stroke， also known as cerebral infarction， is the most common type of stroke. Ischemic stroke is extremely harmful with high rates of morbidity， incidence， disability， and mortality， bringing a huge burden on society and families. As a result， finding new and effective prevention and treatment methods is critical. The pathological mechanism of ischemic stroke is very complex and superimposed， with inflammatory response serving as a critical pathological link in the ischemic stroke cascade injury process. NOD-like receptor 3 （NLRP3） is an intracellular sensor， and the inflammatory cascade mediated by the activated NLRP3 inflammasome can exacerbate ischemic stroke injury through the release of inflammatory factors. Taking the NLRP3 inflammasome as the entry point， a large number of experimental studies on the intervention of traditional Chinese medicine （TCM） in the assembly and activation of NLRP3 inflammasome have been carried out， which proved that Chinese medicinal monomers or prescriptions with the main functions of tonifying deficiency， clearing heat and removing toxin， eliminating phlegm， promoting circulation and resolving stasis can interfere with the assembly and activation of NLRP3 inflammasome， reduce the inflammatory response， and relieve ischemic stroke. This study reviewed the assembly and activation of NLRP3 inflammasome， the mechanism of NLRP3 inflammasome in ischemic stroke， and the prevention and treatment of ischemic stroke by TCM through regulation of the NLRP3 inflammasome， which provides a new entry point for the pathological mechanism of ischemic stroke and a direction for the development of new treatments for ischemic stroke.

Relationship Between NLRP3 Inflammasome and Ischemic Stroke and Intervention Effect of Traditional Chinese Medicine / 中国实验方剂学杂志

Ischemic stroke， also known as cerebral infarction， is the most common type of stroke. Ischemic stroke is extremely harmful with high rates of morbidity， incidence， disability， and mortality， bringing a huge burden on society and families. As a result， finding new and effective prevention and treatment methods is critical. The pathological mechanism of ischemic stroke is very complex and superimposed， with inflammatory response serving as a critical pathological link in the ischemic stroke cascade injury process. NOD-like receptor 3 （NLRP3） is an intracellular sensor， and the inflammatory cascade mediated by the activated NLRP3 inflammasome can exacerbate ischemic stroke injury through the release of inflammatory factors. Taking the NLRP3 inflammasome as the entry point， a large number of experimental studies on the intervention of traditional Chinese medicine （TCM） in the assembly and activation of NLRP3 inflammasome have been carried out， which proved that Chinese medicinal monomers or prescriptions with the main functions of tonifying deficiency， clearing heat and removing toxin， eliminating phlegm， promoting circulation and resolving stasis can interfere with the assembly and activation of NLRP3 inflammasome， reduce the inflammatory response， and relieve ischemic stroke. This study reviewed the assembly and activation of NLRP3 inflammasome， the mechanism of NLRP3 inflammasome in ischemic stroke， and the prevention and treatment of ischemic stroke by TCM through regulation of the NLRP3 inflammasome， which provides a new entry point for the pathological mechanism of ischemic stroke and a direction for the development of new treatments for ischemic stroke.

Lower trapezius myocutaneous flap with latissimus dorsi for repairing parietal and occipital defect after cancer surgery / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the functional outcomes of repairing parietal and occipital defect after surgery for cancer by lower trapezius myocutaneous flap with latissimus dorsi. Methods: Retrospective analyses of eight patients were performed who underwent repairing parietal and occipital defects with dural exposure after surgeries for cancers from January 2015 to January 2020 in Tianjin Institute of Occupational Disease Control and Prevention (Tianjin Workers Hospital) and the Second Hospital of Tianjin Medical University, including 6 males and 2 females aged from 26 to 68 years old. The method for harvesting the lower trapezius myocutaneous flap was improved and thus the lower trapezius myocutaneous flaps with latissimus dorsi were used for repairing the parietal and occipital defects. The area of myocutaneous flap depended on the size of defect. Results: The defects were repaired with the flaps with areas ranging from 12 cm×8 cm to 17 cm×15 cm. Seven flaps survived after surgery and the wounds were healed. Blisters and bruise were observed at the distal end of one flap 2 days after operation, which were cured with dressing change for 10 days. All cases were followed-up for six months, with normal functions of the shoulder joints, aside from mild hypertrophic scar in donor site on the back. Conclusion: It is feasible to use the lower trapezius myocutaneous flap with latissimus dorsi to repair the parietal and occipital defect after surgery for cancer, and the clinical effect is satisfactory.

Mechanistic insights of the controlled release capacity of polar functional group in transdermal drug delivery system: the relationship of hydrogen bonding strength and controlled release capacity

Background@#Hydrogen bonding interaction was considered to play a critical role in controlling drug release from transdermal patch. However, the quantitative evaluation of hydrogen bonding strength between drug and polar functional group was rarely reported, and the relationship between hydrogen bonding strength and controlled release capacity of pressure sensitive adhesive (PSA) was not well understood. The present study shed light on this relationship.@*Methods@#Acrylate PSAs with amide group were synthesized by a free radical-initiated solution polymerization. Six drugs, , etodolac, ketoprofen, gemfibrozil, zolmitriptan, propranolol and lidocaine, were selected as model drugs. drug release and skin permeation experiments and pharmacokinetic experiment were performed. Partial correlation analysis, fourier-transform infrared spectroscopy and molecular simulation were conducted to provide molecular details of drug-PSA interactions. Mechanical test, rheology study, and modulated differential scanning calorimetry study were performed to scrutinize the free volume and molecular mobility of PSAs.@*Results@#Release rate of all six drugs from amide PSAs decreased with the increase of amide group concentrations; however, only zolmitriptan and propranolol showed decreased skin permeation rate. It was found that drug release was controlled by amide group through hydrogen bonding, and controlled release extent was positively correlated with hydrogen bonding strength.@*Conclusion@#From these results, we concluded that drugs with strong hydrogen bond forming ability and high skin permeation were suitable to use amide PSAs to regulate their release rate from patch.

Quality Evaluation of Physical Properties of Ultrafine Granular Powder of Salviae Miltiorrhizae Radix et Rhizoma / 中国实验方剂学杂志

Objective:Taking ultrafine granular powder of Salviae Miltiorrhizae Radix et Rhizoma （UGPSMR） as the research object， to establish a method for evaluating its physical properties. Method:A method was established for measuring the particle size distribution and specific surface area of UGPSMR， and the methodological investigation was carried out. A total of 15 physical indicators ［D90 （particle size value when the cumulative particle distribution reaches 90%）， particle size distribution range， particle size distribution width， bulk density， tap density， intergranular porosity， Carr index， specific surface area， pore volume， angle of repose， tablet angle， Hausner ratio， black to white degree L*， red to green degree a*， yellow to blue degree b*］ were used to characterize the quality attributes of UGPSMR and to construct the physical fingerprint. Multivariate statistical analysis methods such as similarity analysis， cluster analysis （CA）， principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA） were used to evaluate the quality of 11 batches of UGPSMR （S1-S11） produced in different years， and to find out the difference index between samples from different batches. Result:The method for measuring the particle size distribution and specific surface area of UGPSMR was feasible and repeatable. The similarities between the physical fingerprint of 10 batches of samples （S1-S3， S5-S11） from production and control fingerprint of UGPSMR were above 0.85， but the similarity between sample S4 and the control fingerprint was only 0.488. There were some differences in physical property indicators between different batches of UGPSMR， and the characteristic difference indicators were intergranular porosity， specific surface area， pore volume， b*， L*， Carr index， particle size distribution width， respectively. Conclusion:This method can comprehensively evaluate the physical quality attributes of UGPSMR， and can reflect the effect of differences in material basis of the medicinal materials or production process on the physical properties of finished products， and can evaluate quality consistency between batches from the physical state level， which provides new ideas for the quality control of ultrafine granular powder of herbal medicine.

Quality evaluation of angelica broken wall powder based on QbD concept of traditional Chinese medicine / 中国中药杂志

In this paper, angelica broken wall powder(ABWP) was taken as the research object, HPLC fingerprint combined with multi-component determination(ferulic acid, senkyunolide I, coniferyl ferulate, ligustilide and 3-butylidenephthalide), physical fingerprint(D_(90), particle size distribution range, particle size distribution width, bulk density, tap density, inter-particle porosity, Carr index, specific surface area, pore volume, angle of repose, Hausner ratio, loss on drying and hygroscopicity)were used to characterize the quality attribute of ABWP; similarity analysis, cluster analysis, principal component analysis and orthogonal partial least squares discriminant analysis were conducted to construct the quality evaluation method of holographic analysis based on traditional Chinese medicine QbD "4 H mode", in order to evaluate the quality of ABWP from different sources and find out differentiated indicators. The quality evaluation method could be used for scientific, comprehensive evaluation of the quality attribute of ABWP, and the quality consistency evaluation of cell-wall-broken powder of different sources or different processes.It provides new ideas for quality control and research of ultrafine granular powders of traditional Chinese medicine.

Effects of Gait Retraining on Impact Forces, Lower Limb Biomechanics and Leg Stiffness / 医用生物力学

Objective By establishing the intervention mode of 12-week gait retraining (GR) (with the specific aim of changing the habitual running gait), to determine the changes of vertical ground reaction force (vGRF), kinematics and dynamics of hip, knee, ankle joints, as well as stiffness of lower limbs in running before and after GR, and to explore the influence of running posture transformation on impact force and lower limb biomechanics. Methods Vicon motion capture system and Kistler 3D force measurement platform were used to collect the GRF and marker track of 30 runners (15 in experimental group and 15 in control group) before and after GR with the minimalist shoes at a speed of 12 km/h±5%. Results A total of 17 subjects (9 in experimental group and 8 in control group) completed the GR. After GR, the maximum loading rate of both groups decreased significantly, and the maximum loading rate of experimental group was lower than that of control group. The foot strike angle in experimental group decreased significantly after GR, and the plantarflexion angle and hip joint angular extension velocity increased in both groups. The force moment of ankle joint increased in experimental group, and the stiffness of lower limbs was significantly improved in both groups. Conclusions A 12-week GR exercise intervention model was successfully established, with 78% conversion rate (from rearfoot strike to forefoot strike). GR can effectively avoid the peak of impact force, reduce the maximum loading rate, increase the lower limb stiffness, and thus reduce or even avoid the risk of running injury caused by impact force and may provide a possibility for the improvement of running economy.

Optimization of preparation process and evaluation of physical fingerprint of Angelicae Sinensis Radix cellwall broken powder / 中草药

Objective: To optimize the preparation process of Angelicae Sinensis Radix cellwall broken powder (ASR CBP) and evaluate the physical quality of powder. Methods: A HPLC method was established for the determination of five active constituents (ferulic acid, senkyunolide I, coniferyl ferulate, ligustilide and n-butylidenephthalide) of ASR. The Box-Behnken response surface design method was used. The pulverization time, pulverization temperature and sampling capacity in the pulverization process were investigated. The particle size distribution (D90) of the broken wall powder of ASR and the five active ingredients content were used as the response value to construct the response surface model. Under the premise of D90 < 45 μm, the maximum value of the five active ingredients was calculated to optimize the superfine grinding process parameters. A total of 13 physical indicators of D90, coefficient of nonuniformity, particle size distribution width, bulk density, tap density, interparticle porosity, Karl index, specific surface area, pore volume, Hausner ratio, angle of repose, loss on drying and hygroscopicity were used to establish the physical fingerprint of ASR CBP. The similarity evaluation method was used to evaluate the similarity of different batches of ASR CBP. Results: The methodological results of the HPLC method for the determination of the five active ingredients were in accordance with the guidelines. Results of response surface method showed the optimized preparing parameters of ASR CBP technology as follows: 35 min of pulverization time, -10 ℃ of pulverization temperature, and 580 g of sampling capacity. The RSD values between the content and the response surface fitting results of five active ingredients of three batches of cellwall broken powder prepared by the optimal process were all less than 3%. The similarity of the three batches of the optimal process of ASR CBP was above 99.4%. Conclusion: Box-Behnken optimized preparation method of ASR CBP has obvious advantages in retaining the content of active ingredients, especially volatile components. Physical fingerprinting has good practical effects as a tool to evaluate the consistency of physical properties of Chinese material medica powder. The combination of applications helps to achieve a higher quality control level of Chinese medicine cellwall broken powder production.

Overexpression of ULK1 Represents a Potential Diagnostic Marker for Clear Cell Renal Carcinoma and the Antitumor Effects of SBI-0206965.

BACKGROUND: Uncoordinated 51-like kinase 1 (ULK1) plays a vital role in autophagy. ULK1 dysregulation has recently been found in several human cancers. METHODS: mRNA expression levels of ULK1 and clinical information were analysed from The Cancer Genome Atlas data. ULK1 expression levels were verified in 36 paired fresh ccRCC tissue specimens by western blot analysis. Expression of ULK1 was knockdown by shRNA lentivirus. ULK1 activity was inhibited by SBI-0206965. The effect of inhibition of ULK1 was measured by detecting the apoptotic rate, autophagy, and the ratio of ROS and NADPH. The efficacy of SBI-0206965 in vivo was assessed by the murine xenograft model. FINDINGS: ULK1 mRNA expression was significantly upregulated in clear cell renal cell carcinoma (ccRCC) and overexpression of ULK1 correlated with poor outcomes. We found that ULK1 was highly expressed in 66.7% of ccRCC tumours (p < 0·05). Knockdown of ULK1 and selective inhibition of ULK1 by SBI-0206965 induced cell apoptosis in ccRCC cells. We demonstrated that SBI-0206965 triggered apoptosis by preventing autophagy and pentose phosphate pathway (PPP) flux. Furthermore, blocking the kinase activity of ULK1 with SBI-0206965 resulted in a level of anticancer effect in vivo. INTERPRETATION: Taken together, our results suggested that ULK1 was upregulated in ccRCC tumours and may be a potential therapeutic target. Therefore, SBI-0206965 should be further considered as an anti-ccRCC agent. FUND: This work was supported in part by The National Natural Science Foundation of China (No. 81570748) and Natural Science Foundation of Fujian Province (No. 2018J01345, 2017XQ1194).

Experimental study on induction of cognitive function and heart rate variability by simulated flight / 解放军医学杂志

Objective Through the establishment of the model of mental fatigue which was induced by continuous mental workload,compare the changes in cognitive function before and after simulated flight and investigate the pattern of heart rate variability (HRV) during the period of simulated flight,thus providing the foundation of screening objective indices for monitoring mental fatigue.Methods A total of 30 participants were informed to take part in a simulated flight for 4 hours.They were arranged to complete the Stanford Sleepiness Scale (SSS) and two cognitive tests,including psychomotor vigilance task (PVT) and shifting attention test (SAT) before and after simulated flight severally.HRV was recorded continuously during the period of simulated flight.Results After simulated flight,the scores of SSS significantly increased (P＜0.05) and mean reaction times to PVT and SAT were longer compared with presimulated flight (P＜0.05).Heart rate (HR) and RMSSD considered as the time domain index of HRV showed significant difference during the period of simulated flight (F=9.81,F=4.75,respectively,both P＜0.05).The results indicate that HR declined and RMSSD of HRV increased significantly,while no significant differences were found in other time domain component and the frequency domain component of HRV.Conclusions The mean reaction times of cognitive tests are sensitive indices to monitor mental fatigue.However,when the time domain component and the frequency domain component of HRV are applied into monitoring mental fatigue,there are still some limitations in different conditions.

The establishment of positive and negative evaluative conditioning reflex of neutral facial expression / 中华行为医学与脑科学杂志

Objective To examine the effect of positive and negative evaluative conditioning (EC) on neutral faces.Methods The experiment consisted of three phases:baseline phase,conditioning phase,and re-evaluative phase,in which 41 college students participated,watching sequences of neutral faces (CS) pairing to either a positive stimulus (USpos) or a negative stimulus (USneg).Their emotional experiences (valence and arousal) and physiological reactivity (eyeblink startle reflex and skin conductance) were recor ded.Results (1) In the re-evaluative phase,CSpos was rated significantly more positive than CSneg and CSneut,while CSneg was rated significantly more negative than CSneut (CSpos (5.05± 1.24),CSneg (3.73± 1.48),CSneut (4.46± 1.04),P＜0.05).(2)In the re-evaluative phase,the mean startle eyeblink response magnitude(T score) to CSpos was significantly smaller than the responses elicited by CSneg and CSneut (CSpos (45.04±5.56),CSneg (51.44±9.30),CSneut (54.52± 10.60),P＜0.01).Conclusion The findings suggest that neutral faces can acquire valences and approach motivation through EC.

Argonaute 2 promotes angiogenesis via the PTEN/VEGF signaling pathway in human hepatocellular carcinoma.

AIM: Argonaute2 (AGO2) protein is the active part of RNA-induced silencing complex, cleaving the target mRNA strand complementary to their bound siRNA. An increasing number of miRNAs has been identified as essential to angiogenesis of hepatocellular carcinoma (HCC). In this study we investigated how AGO2 affected HCC angiogenesis. METHODS: Human HCC cell lines HepG2, Hep3B, Huh7, SMMC-7721, Bel-7404, MHCC97-H and LM-3, and human umbilical vein endothelial cells (HUVEC) were tested. The expression of AGO2 in HCC cells was knocked down with siRNA and restored using recombinant adenovirus expressing Ago2. The levels of relevant mRNAs and proteins were examined using RT-PCR, Western blot and EILSA. Nude mice were implanted with Huh7 or SMMC-7721 cells, and tumor volumes were measured. After the mice were euthanized, the xenograft tumors were used for immunohistological analysis. RESULTS: In 6 HCC cell lines, AGO2 protein expression was significantly correlated with VEGF expression (r=+0.79), and with VEGF secretion (r=+0.852). Knockdown of Ago2 in Huh7 cells and SMMC-7721 cells substantially decreased VEGF expression, whereas the restoration of AGO2 reversed both VEGF expression and secretion. Furthermore, knockdown of Ago2 significantly up-regulated the expression of PTEN (a tumor suppressor involved in the inhibition of HCC angiogenesis), and vice versa. Moreover, the specific PTEN inhibitor bisperoxovanadate (7, 14, 28 nmol/L) dose-dependently restored the expression of VEGF and the capacity of HCC cells to induce HUVECs to form capillary tubule structures. In the xenograft nude mice, knockdown of Ago2 markedly suppressed the tumor growth and decreased PTEN expression and CD31-positive microvascular in the xenograft tumors. CONCLUSION: A direct relationship exists between the miRNA processing machinery AGO2 and HCC angiogenesis that is mediated by the AGO2/PTEN/VEGF signaling pathway. The results suggest the high value of Ago2 knockdown in anti-angiogenesis therapy for HCC.