Syndrome Differentiation of Chinese Medicine in Mars 500 Long-Term Closed Environment.

OBJECTIVE: To summarize and elucidate the characteristics and evolvement of Chinese medicine (CM) patterns reflecting the physical and mental conditions of participants in the Mars 500 long-term closed environment. METHODS: The DS01-T Digital TCM Four-Diagnostic Instrument and CM Inquiring Diagnostic Questionnaire were used to collect information from 6 participants in the Mars 500 International Joint Research Project, through diagnostic methods of observation, palpation and inquiry according to CM theory. During the 520 days of the experiment, data collection was performed 37 times; a total of over 400 digital images of tongues and facial complexion and over 20,000 data were collected. These data were then analyzed by a team of experts in CM, statistics, and data mining. RESULTS: The CM pattern evolvement of participants in the long-term closed environment followed some common trends. Qi deficiency was the main CM pattern observed, with individual features depending on constitutional differences [manifested in varying degrees of accompanying patterns of Gan (Liver) qi stagnation, Pi (Spleen) deficiency, dampness encumbering, or yin deficiency]. CONCLUSION: The research has verified the effectiveness of CM syndrome differentiation based on the four diagnostic methods, which should serve as a solid foundation for observation, monitoring, and intervention in regard to the health conditions of astronauts in long-term space flights in the future.

Serum HER2 as a predictive biomarker for tissue HER2 status and prognosis in patients with gastric cancer.

AIM: To investigate the association between serum human epidermal growth factor receptor 2 (HER2) extracellular domain (ECD) and tissue HER2 status, and the prognostic value of serum HER2 ECD in patients with gastric cancer. METHODS: A total of 239 patients with gastric cancer were enrolled from December 2012 to June 2013. Serum HER2 ECD was determined by chemiluminescent assay, and tissue HER2 status was evaluated by immunohistochemistry and fluorescence in situ hybridization assay. A receiver operating characteristic (ROC) curve was plotted to identify the optimal cut-off value for serum HER2 ECD assay for predicting survival in gastric cancer patients. RESULTS: Serum HER2 ECD was significantly correlated with tissue HER2 status (P < 0.001), tumor size (P < 0.001), and intestinal type of gastric cancer (P = 0.021). Serum HER2 ECD levels differed significantly between patients with HER2-positive tissue expression and those with HER2-negative tissue expression. ROC analysis yielded an area under the curve value of 0.79 (95%CI: 0.71-0.87, P < 0.001), with a sensitivity and specificity of 0.54 (95%CI: 0.37-0.70) and 0.93 (95%CI: 0.88-0.96), respectively. With a cut-off value of 24.75 ng/mL, high serum HER2 ECD had a negative impact on overall survival of the patients (HR: 1.93, 95%CI: 1.32-4.38, P = 0.006). CONCLUSION: Serum HER2 ECD could be a highly specific surrogate biomarker for tissue HER2 status in gastric cancer. Optimal cut-off criteria for predicting survival should be established.

Evaluation of the health status of six volunteers from the Mars 500 project using pulse analysis.

OBJECTIVE: To comprehensively evaluate the health status of 6 volunteers from the Mars 500 Project through analyzing their pulse graphs and determining the changes in cardiovascular function, degree of fatigue and autonomic nervous function. METHODS: Six volunteers were recruited; all were male aged 26-38 years (average 31.83±4.96 years). Characteristic parameters reflflecting the status of cardiovascular functions were extracted, which included left ventricular contraction, vascular elasticity and peripheral resistance. The degree of fatigue was determined depending on the difference between the calendar age and biological age, which was calculated through the analysis of blood pressure value and characteristic parameters. Based on the values of pulse height variation and pulse time variation on a 30-s pulse graph, autonomic nervous function was evaluated. All parameters examined were marked on an equilateral polygon to form an irregular polygon of the actual fifigure, then health status was evaluated based on the coverage area of the actual fifigure. RESULTS: The results demonstrated: (1) volunteers developed weakened pulse power, increased vascular tension and peripheral resistance, and slight decreased ventricular systolic function; (2) the degree of fatigue was basically mild or moderate; and (3) autonomic nervous function was excited but generally balanced. CONCLUSIONS: These volunteers were in the state of sub-health. According to Chinese medicine theories, such symptoms are mainly caused by the weakening of healthy qi, Gan (Liver) failing in free coursing, and disharmony between Gan and Wei (Stomach), which manifests as a weak and string-like pulse.

Syndrome Differentiation Analysis on Mars500 Data of Traditional Chinese Medicine.

Mars500 study was a psychological and physiological isolation experiment conducted by Russia, the European Space Agency, and China, in preparation for an unspecified future manned spaceflight to the planet Mars. Its intention was to yield valuable psychological and medical data on the effects of the planned long-term deep space mission. In this paper, we present data mining methods to mine medical data collected from the crew consisting of six spaceman volunteers. The synthesis of the four diagnostic methods of TCM, inspection, listening, inquiry, and palpation, is used in our syndrome differentiation. We adopt statistics method to describe the syndrome factor regular pattern of spaceman volunteers. Hybrid optimization based multilabel (HOML) is used as feature selection method and multilabel k-nearest neighbors (ML-KNN) is applied. According to the syndrome factor statistical result, we find that qi deficiency is a base syndrome pattern throughout the entire experiment process and, at the same time, there are different associated syndromes such as liver depression, spleen deficiency, dampness stagnancy, and yin deficiency, due to differences of individual situation. With feature selection, we screen out ten key factors which are essential to syndrome differentiation in TCM. The average precision of multilabel classification model reaches 80%.

Hemodynamic assessment and computation on vertebral artery stenosis.

Cerebral vascular diseases are associated with cerebral hemodynamic parameter, which is difficult to observe and examine. This paper has proposed a new modeling method based on network and hemodynamics. The harmonic solution to the 18 branches of the circle of Willis is acquired through the plane network. We use this method to explain the development processes of vertebral artery diseases, and the hemodynamic assessment of vertebral artery stenosis have been done to prove this method.

Fatsioside A inhibits the growth of glioma cells via the induction of endoplasmic reticulum stress-mediated apoptosis.

Malignant gliomas are a common type of primary tumor of the central nervous system. In spite of current intensive therapy, the prognosis of patients with malignant glioma remains poor, hence the development of novel therapeutic modalities is necessary. Cell apoptosis is a frequent target in the development of anti­cancer drugs. Fatsioside A, a novel baccharane­type triterpenoid glycoside, is extracted from the fruits of Fatsia japonica. Previous studies have shown that Fatsioside A induces growth inhibition, cell cycle arrest and apoptosis in C6 rat glioma cells and U251 human glioma cells. However, to the best of our knowledge, no detailed studies have reported its effect on U87MG glioma cells and its exact mechanisms remain unknown. In the current study, the growth inhibitory effect of Fatsioside A on U87MG cells was evaluated and the underlying molecular mechanisms were explored. Through the use of flow cytometry and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, it was determined that Fatsioside A markedly inhibits the growth of U87MG cells. Mechanistic studies demonstrated that Fatsioside A induces growth inhibition of U87MG cells via the induction of endoplasmic reticulum (ER) stress, which was supported by the upregulation of ER stress markers, including elevated levels of phosphorylation of PERK and eIF2α, the increased expression levels of CHOP and the accelerated cleavage of caspase­4. The downregulation of CHOP via CHOP­specific siRNA reduced the growth­inhibitive effect of Fatsioside A on U87MG cells, further confirming the role of the ER stress response in mediating Fatsioside A­induced growth inhibition. In conclusion, Fatsioside A inhibits glioma cell growth via the induction of ER stress­mediated apoptosis. This may provide a molecular basis for the development of Fatsioside A into a drug candidate for the treatment of malignant glioma.

Impact of 60 days of 6° head down bed rest on cardiopulmonary function, and the effects of Taikong Yangxin Prescription as a countermeasure.

OBJECTIVE: To study the changes in cardiopulmonary function induced by mid/long-term simulated microgravity with 6° head down bed rest (HDBR), and the effects of Taikong Yangxin Prescription (, TYP) as a countermeasure. METHODS: Fourteen healthy male volunteers were randomly divided into a control group and a Chinese medicine (CM) group (7 in each group) by a random digital table based on their body weight. Both groups underwent 6° HDBR for 60 days. Subjects in the CM group received daily TYP pills and subjects in the control group received daily placebo pills. Cardiac systolic and pumping functions were measured by echocardiography before HDBR; on days 20, 42, and 57 of HDBR; and on day 3 of recovery after HDBR (R+3). Cardiopulmonary functional reserve and exercise capacity were evaluated before HDBR, on day 29, and on day R+3 by exercise testing. RESULTS: The heart rate (HR) increased gradually during HDBR. The HR was significantly higher on day 57 than before HDBR in the control group (P<0.05), but did not increase significantly in the CM group. The stroke volume/stroke volume index, ejection fraction, and left ventricular fractional shortening tended to decrease over time in the control group, but not in the CM group. These parameters were significantly higher in the CM group than in the control group on day 42 (P<0.05 or <0.01). Exercise testing showed that maximum O2 consumption (VO2max), metabolic equivalents, relative O2 consumption (VO2), O2 pulse, and exercise duration were significantly lower on day 29 than before HDBR in the control group, but not in the CM group. CONCLUSIONS: Sixty days of 6° HDBR induced a reduction in cardiac systolic and pumping functions, and reduced cardiopulmonary functional reserve and exercise capacity. Administration of TYP significantly improved cardiac systolic and pumping functions, and maintained cardiopulmonary functional reserve and exercise capacity.

Effects of subdiaphragmatic cardiac compression on cardiac arrest during liver transplantation.

Cardiac arrest during upper abdominal surgery such as liver transplantation is a rare but very severe complication. Traditional external cardiac compression has been the mainstay of basic life support in general circumstances. Subdiaphragmatic cardiac compression (SDCC), with no incision in the diaphragm, may be a more effective measure. This maneuver can provide more effective and timely cardiac compression via the already open abdomen in surgery and not add extra trauma. This method can provide a quicker and more effective means of circulation support for intraoperative cardiac arrest patients without adding new injuries. Five cases are reported and all the patients had return of spontaneous circulation (ROSC). This is the first report of the SDCC method.

[Effect of previous statins on prognosis of octogenarian patients with coronary heart disease with percutaneous coronary stenting].

OBJECTIVE: To evaluate the effect of statin pretreatment on prognosis of octogenarian patients with coronary heart disease with percutaneous coronary intervention (PCI). METHODS: A total of 90 patients aged at 85 years old and over with coronary heart disease (CAD) undergoing stenting were enrolled. The duration of statin, hospitalization and one-year clinical follow-up outcome including all-cause mortality, major adverse cardiac event (MACE), stroke and other major hemorrhages were collected and analyzed. RESULTS: Among these patients, 33 (36.7%) received a statin pre-treatment for at least 2 days and 57 (63.3%) did not. Patients on a statin pre-treatment were more likely to have hypertension, hyperlipidemia and a history of myocardial infraction and PCI. The procedure characteristics were similar between two groups. Despite the higher risk profile, the patients on a statin pre-treatment had a lower hospitalization MACE rate (3.0% vs 10.5%, P = 0.05). However, at one year, the patients on a statin pre-treatment had a similar MACE rate (6.1% vs 3.8%, P = 0.07) as the other group. CONCLUSION: The statin pretreatment in octogenarian CAD patients with PCI may be associated with a reduced hospitalization MACE rate.

Neural correlates of traditional Chinese medicine induced advantageous risk-taking decision making.

This fMRI study examined the neural correlates of the observed improvement in advantageous risk-taking behavior, as measured by the number of adjusted pumps in the Balloon Analogue Risk Task (BART), following a 60-day course of a Traditional Chinese Medicine (TCM) recipe, specifically designed to regulate impulsiveness in order to modulate risk-taking behavior. The 14 participants recruited for this study were randomly assigned to the experimental and control groups and the TCM recipe (Panax, 520 mg; Astragalus membranaceous Bunge, 520 mg; Masnetitum, 840 mg; Ostrea gigas Thumb, 470 mg; Thinleaf Milkwort Root Radix Polygalae, 450 mg; and Os Draconis, 470 mg) was administered, as a diet supplement, to the seven participants in the experimental group. The neural activity of the two groups was monitored by a 3T MRI scanner, before and after the 60-day treatment. Associated with the improved advantageous risk-taking behavior seen in the experimental group, significantly stronger blood oxygenation level dependent (BOLD) responses were observed in the bilateral dorsolateral prefrontal cortex (DLPFC), left putamen, left thalamus, right insula, and right anterior cingulate cortex (ACC), regions which have previously been reported as being involved in risk-taking decision making. The effect of the TCM in improving advantageous risk-taking decision making appears to have been related to the enhanced efficiency of the cognitive affective system, the PFC-ACC-insula-striatum network, which functions to inhibit impulsiveness, to sensitize reward-related information, and to allow the opportunity, during risk estimation, to evaluate potential gains and losses. The findings of this study suggest that interventions acting on factors modulating risk-taking decision making could have a beneficial effect in terms of optimizing risk-taking behavior.

[Regulative effects of Chinese herb-compound on blood rheology and circulatory system of rabbits under simulated weightlessness].

OBJECTIVE: To investigate effects of Chinese herb-compound on blood rheology and circulatory system of rabbits under simulated weightlessness in order to provide bases for protecting against the influence of simulated weightlessness on cardiovascular function. METHOD: Rabbits were exposed to head-down tilt (HDT -20 degrees) for 9 d to simulate weightlessness. The effect of Chinese herb-compound on indices related to blood rheology, blood-fat and orthostatic tolerance in these rabbits were examined. RESULT: After head-down tilt, hematocrit value and red blood cells deformability decreased significantly; cholesterol and low density lipoprotein increased markedly; plasma fibrinogen content and triglyceride showed increasing trend. Administration of the Chinese herb-compound didn't improve the blood rheology indices, but showed a trend to decrease triglyceride and to inhibit the increase of cholesterol. In the head-up tilt (HUT) plus lower body negative pressure (LBNP) experiment, orthostatic tolerance time of the rabbits in the control group decreased, and myocardial ischemic changes in ECG, such as dropped ST segment, inverse T wave, and arrhythmia were observed. While in the Chinese herb-compound group, the heart rate of the rabbits kept smooth, ischemic changes in ECG were not clear, and orthostatic tolerance time increased. CONCLUSION: The Chinese herb-compound shows an effect of preventing orthostatic tolerance from decreasing, and improves blood-fat metabolism. It regulates different human systems on the whole, and increases ability of adaptation to ill environment.

Effects of L.F04, the active fraction of Lycopus lucidus, on erythrocytes rheological property.

OBJECTIVE: To study the effects of L.F04, the active fraction of Lycopus lucidus, on erythrocytes rheological property so as to investigate its mechanism in promoting blood circulation and removing blood stasis. METHOD: The effects of L.F04 (used for treatment for 10 days in different dosages) on deformability, aggregation and membrane liquidity of erythrocytes (MLE) as well as whole blood apparent viscosity (eta(b)) were examined on the basis of rat model of blood-stasis syndrome induced by venous injection of high molecular weight dextran. RESULT: As compared with the normal control group, the model group's RBC deformability and MLE were lower, and the aggregation of erythrocytes and eta(b) were higher. Compared with the model group, both L.F04 0.612 g/kg and 0.306 g/kg showed significant effect in improving deformability and inhibiting aggregation of red blood cells (RBC) and reducing blood viscosity. The trend of improving MLE was also shown. CONCLUSION: L.F04 could significantly improve the abnormal rheological property of erythrocytes.

[Biological effects of space flight on several opportunistic pathogenic bacteria and biodestructive fungi].

OBJECTIVE: To investigate biological effects of space flight on several conditional pathogenic bacteria and biodestructive fungi. METHOD: Several potentially pathogenic or biodegrading microorganisms, including bacteria, actinomyces and fungi, were carried on-board spacecraft for 7 d. Some of the biological characteristics were studied by using general microbial test technology after recovery. RESULT: In space condition, survival and growth rate were promoted, and soluble pigments were produced, while morphological properties were changed differently. The antibiotic-sensitivity of certain strains decreased, while most of them showed no changes. CONCLUSION: The reproduction ability and growth rate of these microorganisms are promoted after being carried into space, and morphological differentiation increase. The resistance to antibiotics is stable.

Effects of active fractions from Lycopus lucidus L. F04 on platelet aggregation and thrombus formation.

OBJECTIVE: To study the effect of active fractions from Lycopus lucidus (L. F04) on platelet aggregation and thrombus formation so as to investigate its mechanism of promoting blood circulation and removing blood stasis. METHOD: The effects of Lycopus lucidus L. F04 on platelet aggregation induced by ADP in vivo, and thrombosis of artery-vein by-pass and thrombus formed in circuitous loop in vitro were examined using the blood stasis animal model of rats made by injecting high molecular weight dextran (HMWD). RESULT: The increase of maximum platelet aggregation rate induced by ADP in vivo in HMWD model was evidently inhibited with 0.408 g/kg or 0.204 g/kg or L. F04, and the effect showed a trend of concentration-dependence. As compared with the control, the thrombus weight in rat model of blood stasis increased clearly and its length showed only a trend of increase. Both 0.408 g/kg and 0.204 g/kg of L. F04 had the effect of resisting the thrombus formation, while 0.408 g/kg showed better effects of reducing the thrombus dry weight and wet weight. Both 0.408 g/kg and 0.204 g/kg of L. F04 could inhibit the thrombosis in artery-vein by-pass; the inhibition rates were 27.41% and 27.14% respectively. CONCLUSION: Lycopus lucidus L. F04 could significantly inhibit platelet aggregation and thrombus formation.

[Effects of Qiang Gu Kang Wei prescription on morphology of bone in rats under simulated weightlessness].

OBJECTIVE: To investigate effects of Qiang Gu Kang Wei prescription on bone morphology in tail-suspended rats. METHOD: Rats were tail-suspended (-30 degrees) for 21 d to simulate weightlessness. The effects of this prescription on thickness of periost and cortex at epiphyseal plate of tibial shaft and 3 mm under it were examined. The effects of this prescription on histology and ultrastructure of tibia were also observed. RESULT: Compared with the normal control, cortex at both epiphyseal plate of tibial shaft and 3 mm under it in suspended rats thinned significantly (P<0.01 or P<0.05). Histological observation showed that in bone of suspended rats, uncalcific matrix was more, bone cells' number was lower and their appearance was more infantile, osteoblasts were less and smaller, while osteoclasts were more and larger, haversian system of transection also showed more irregular than in bone of normal control. Ultrastructure observation showed that the function of osteoblasts was inhabited and that of osteoclasts was active. All the three doses groups of the prescription could increase cortex at either epiphyseal plate of tibial shaft or 3 mm under it (P<0.01 or P<0.05) compared with the tail-suspended group. The appearance of bone in the three groups was improved as well under optical or electron microscope. CONCLUSION: This prescription could improve abnormal change in bone morphology resulted from being tail-suspended in rats and make it normal.

[Effects of "Qiang Gu Kang Wei" compound prescription on biochemical indices of bone and related organs in rats under simulated weightlessness].

OBJECTIVE: To investigate effects of "Qiang Gu Kang Wei" prescription on biochemical indices of bone and related organs in tail-suspended rats. METHOD: Rats were tail-suspended (-30 degrees) for 21 d to simulate weightlessness. The effect of this prescription on biochemical indices such as Ca, P in serum, osteocalcin (BGP) in serum and bone, oxyproline hydroxyproline (Hyp) in bone, alkaliphosphatase (ALP) in serum, small intestine and bone in these rats were examined. RESULT: Comparing with the normal control, serum Ca decreased significantly (P<0.05) while serum P showed only a trend to decrease, at the same time BGP dropped in both serum and bone (P<0.05) and Hyp dropped only in bone (P<0.05). There was significant decrease of ALP activity in serum, small intestine and bone (P<0.01 or P<0.05) in suspended rats. The prescription showed different effects with different doses. In all the three dose groups (30 g/kg, 20 g/kg, 10 g/kg) Ca and P in serum levels increased (P<0.01 or P<0.05), BGP in serum and bone improved (P<0.05) or showed only a trend to increase. ALP activity increased in serum, small intestine and bone (P<0.05). Increase of Hyp in bone was found in the middle and the small dose groups (P<0.05). CONCLUSION: This prescription shows an effect of improving biochemical indices in bone and related organs such as serum and small intestine in tail-suspended rats. But no distinct concentration-dependence was found.

[Effects of "Qiang Gu Kang Wei" compound prescription on bone metabolism in rats under simulated weightlessness].

OBJECTIVE: To investigate the effect of "Qiang Gu Kang Wei" prescription on bone metabolism in simulated weightless rats. METHOD: Male SD rats were randomly divided into five groups: 1) free active control (FAC); 2) tail-suspended control (TS); 3) tail-suspended and treated with large dose of the prescription (TS + L) (30 g/kg); 4) tail-suspended and treated with middle dose of the prescription (TS + M) (20 g/kg); 5) tail suspended and treated with small dose of the prescription (TS + S) (10 g/kg). The experiment lasted 3 weeks. The effect of the prescription on bone biomechanical properties, bone density, bone mineral contents, and bone biochemical markers of bone metabolism were examined. RESULT: Bone biomechanical properties, bone density, total and bound bone gla protein (BGP) of serum all increased significantly in three groups treated with the prescription. CONCLUSION: "Qiang Gu Kang Wei" prescription prevents bone loss, hence maintains bone density and bone biomechanical properties under simulated weightlessness.

[Effects of Qiang Gu Kang Wei compound on hemorheology in tail-suspended rats].

Objective. To investigate the effects of Qiang Gu Kang Wei compound on hemorheology in tail-suspended rats. Method. Rats were tail-suspended (-30 degrees) for 21 d to simulate weightlessness. The effect of the compound on erythrocyte sedimentation rate (ESR), hematocrit value (HCT), plasma fibrinogen content (PFC), blood viscosity, red blood cells deformability and erythrocytes aggregation were examined. Result. PFC, whole blood reducing viscosity (eta h), whole blood viscosity (eta b), erythrocyte rigid index (IR) and maximum aggregation index (MAXD) increased significantly (P<0.01 or P<0.05 ) and maximum deformity index (DImax) (P<0.01) decreased significantly in suspended rats as compared with the normal control. Different doses of the compound showed different effects. The small dose group (10 g/kg) inhabited eta h and eta b (P<0.01 or P<0.05) of all shear rates, abnormal IR and MAXD (P<0.01); The middle dose group (20 g/kg) decreased PFC (P<0.01); The big dose group (30 g/kg) inhabited eta h and eta b (P<0.01 or P<0.05) of high shear rates, decreased IR (P<0.01), and improved DImax (P<0.01). Conclusion. This compound could improve hemorheology in tail-suspended rats. But there was no concentration-dependence.

[Effects of active fractions from Lycopus lucidus L. F04 on erythrocyte rheology [correction of erythrocyterheology]].

Objective. To study the effects of active fractions from Lycopus lucidus (L. F04) on erythrocyte rheology so as to investigate its mechanism of promoting blood circulation and removing blood stasis. Method. The effects of L. F04 on erythrocytes deformability, aggregation, liquidity of membrane were examined in the present study and the blood stasis animal model of rats made by injecting high molecular weight dextran (HMWD) was used. Result. HMWD injection decreased red blood cells deformability (P<0.05) and liquidity of membrane (P<0.01) and increased erythrocytes aggregation (P<005). Compared with the model, both L. F04 0.612 g/kg and 0.306 g/kg improved red blood cells deformability (P<0.05), inhibited erythrocytes aggregation (P<0.05), and showed the trend of improving liquidity of membrane. But there was no concentration-dependence. Conclusion. L. F04 can significantly improve the deviant erythrocyte rheology characteristics.

[Effects of pamidronate disodium (Bonin) combined with chemotherapy on bone pain in multiple myeloma].

Objective. To evaluate the therapeutic effects of Disodium Pamidronate (Bonin) on bone pain in multiple myeloma. Method. 18 patients received only chemotherapy and 16 patients with addition of Bonin were compared. Result. The bone pain was significantly relieved both in chemotherapy alone group and in the combination group of Bonin with chemotherapy after treatment (P<0.01, as compared with before therapy). However, the effects of combination group were more dramatical than that of the other group (P<0.05). No obvious side-effects were observed except mild fever in one patient in the combination group. Conclusion. Bonin, as a safe and effective Bisphosphonates preparation, could relieve bone pain in multiple myeloma more effectively when combined with chemotherapy.