[Study on mechanism of Rehmanniae Radix Praeparata for treatment of osteoarthritis based on network pharmacology and molecular docking].

The mechanism of Rehmanniae Radix Praeparata against osteoarthritis was investigated based on network pharmacology, molecular docking, and in vitro experiments in the present study. Osteoclast models were established via receptor activator of nuclear factor-κB ligand(RANKL) and macrophage colony-stimulating factor(M-CSF) inducing RAW264.7 cells. Further, the influence of Rehmanniae Radix Praeparata on the activity of tartrate-resistant acid phosphatase(TRAP) was evaluated and the efficacy of Rehmanniae Radix Praeparata in the treatment of osteoarthritis was verified. The active components of Rehmanniae Radix Praeparata were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and literature, and the potential targets of the components were collected from SwissTargetPrediction. Osteoarthritis disease targets were searched in Online Mendelian Inheritance in Man(OMIM), Therapeutic Target Database(TTD), GeneCards, and DisGeNET. The intersection targets of Rehmanniae Radix Praeparata and osteoarthritis were obtained by Venny platform. The protein-protein interaction(PPI) network was constructed by Cytoscape 3.8.2, and key targets were obtained based on topology algorithm. The Database for Annotation, Visualization and Integrated Discovery(DAVID) was used to perform Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Finally, the mRNA expression of the key targets was determined by RT-qPCR and the binding activity between the components and key targets was validated by molecular docking. The results showed that Rehmanniae Radix Prae-parata inhibited the TRAP activity, thus inhibiting bone resorption by osteoclasts and treating osteoarthritis. By network pharmacology, 14 active components of Rehmanniae Radix Praeparata and 126 intersection targets were obtained. The network pharmacology enrichment results revealed 432 biological processes and 139 signaling pathways. Key targets such as proto-oncogene tyrosine-protein kinase Src(SRC), signal transducer and activator of transcription 3(STAT3) and transcription factor p65(RELA) were obtained according to the degree in topological analysis. SRC was highly expressed in osteoclasts, which accelerated the development of osteoarthritis. Therefore, SRC was selected for subsequent verification, and Rehmanniae Radix Praeparata decreased the gene expression level of SRC. The molecular docking showed that acteoside, isoacteoside, raffinose had good bonding activity with SRC, suggesting that they might be the critical components in treating osteoarthritis. In conclusion, Rehmanniae Radix Praeparata can inhibit bone resorption by osteoclasts and balance the metabolism of articular cartilage and subchondral bone via acting on SRC, thus playing a therapeutic role in osteoarthritis. In addition, Rehmanniae Radix Praeparata may exert overall efficacy on osteoarthritis through other targets such as STAT3 and RELA, and other related pathways such as PI3 K-AKT and IL-17 signaling pathways.

A multi-step approach for tongue image classification in patients with diabetes.

BACKGROUND: In China, diabetes is a common, high-incidence chronic disease. Diabetes has become a severe public health problem. However, the current diagnosis and treatment methods are difficult to control the progress of diabetes. Traditional Chinese Medicine (TCM) has become an option for the treatment of diabetes due to its low cost, good curative effect, and good accessibility. OBJECTIVE: Based on the tongue images data to realize the fine classification of the diabetic population, provide a diagnostic basis for the formulation of individualized treatment plans for diabetes, ensure the accuracy and consistency of the TCM diagnosis, and promote the objective and standardized development of TCM diagnosis. METHODS: We use the TFDA-1 tongue examination instrument to collect the tongue images of the subjects. Tongue Diagnosis Analysis System (TDAS) is used to extract the TDAS features of the tongue images. Vector Quantized Variational Autoencoder (VQ-VAE) extracts VQ-VAE features from tongue images. Based on VQ-VAE features, K-means clustering tongue images. TDAS features are used to describe the differences between clusters. Vision Transformer (ViT) combined with Grad-weighted Class Activation Mapping (Grad-CAM) is used to verify the clustering results and calculate positioning diagnostic information. RESULTS: Based on VQ-VAE features, K-means divides the diabetic population into 4 clusters with clear boundaries. The silhouette, calinski harabasz, and davies bouldin scores are 0.391, 673.256, and 0.809, respectively. Cluster 1 had the highest Tongue Body L (TB-L) and Tongue Coating L (TC-L) and the lowest Tongue Coating Angular second moment (TC-ASM), with a pale red tongue and white coating. Cluster 2 had the highest TC-b with a yellow tongue coating. Cluster 3 had the highest TB-a with a red tongue. Group 4 had the lowest TB-L, TC-L, and TB-b and the highest Per-all with a purple tongue and the largest tongue coating area. ViT verifies the clustering results of K-means, the highest Top-1 Classification Accuracy (CA) is 87.8%, and the average CA is 84.4%. CONCLUSIONS: The study organically combined unsupervised learning, self-supervised learning, and supervised learning and designed a complete diabetic tongue image classification method. This method does not rely on human intervention, makes decisions based entirely on tongue image data, and achieves state-of-the-art results. Our research will help TCM deeply participate in the individualized treatment of diabetes and provide new ideas for promoting the standardization of TCM diagnosis.

Research of the Distribution of Tongue Features of Diabetic Population Based on Unsupervised Learning Technology.

Background: The prevalence of diabetes increases year by year, posing a severe threat to human health. Current treatments are difficult to prevent the progression of diabetes and its complications. It is imperative to carry out individualized treatment of diabetes, but current diagnostic methods are difficult to specify an individualized treatment plan. Objective: Clarify the distribution law of tongue features of the diabetic population, and provide the diagnostic basis for individualized treatment of traditional Chinese medicine (TCM) in the treatment of diabetes. Methods: We use the TFDA-1 tongue diagnosis instrument to collect tongue images of people with diabetes and accurately calculate the color features, texture features, and tongue coating ratio features through the Tongue Diagnosis Analysis System (TDAS). Then, we used K-means and Self-organizing Maps (SOM) networks to analyze the distribution of tongue features in diabetic people. Statistical analysis of TDAS features was used to identify differences between clusters. Results: The silhouette coefficient of the K-means clustering result is 0.194, and the silhouette coefficient of the SOM clustering result is 0.127. SOM Cluster 3 and Cluster 4 are derived from K-means Cluster 1, and the intersections account for (76.7% 97.5%) and (22.3% and 70.4%), respectively. K-means Cluster 2 and SOM Cluster 1 are highly overlapping, and the intersection accounts for the ratios of 66.9% and 95.0%. K-means Cluster 3 and SOM Cluster 2 are highly overlaid, and the intersection ratio is 94.1% and 82.1%. For the clustering results of K-means, TB-a and TC-a of Cluster 3 are the highest (P < 0.001), TB-a of Cluster 2 is the lowest (P < 0.001), and TB-a of Cluster 1 is between Cluster 2 and Cluster 3 (P < 0.001). Cluster 1 has the highest TB-b and TC-b (P < 0.001), Cluster 2 has the lowest TB-b and TC-b (P < 0.001), and TB-b and TC-b of Cluster 3 are between Cluster 1 and Cluster 2 (P < 0.001). Cluster 1 has the highest TB-ASM and TC-ASM (P < 0.001), Cluster 3 has the lowest TB-ASM and TC-ASM (P < 0.001), and TB-ASM and TC-ASM of Cluster 2 are between the Cluster 1 and Cluster 3 (P < 0.001). CON, ENT, and MEAN show the opposite trend. Cluster 2 had the highest Per-all (P < 0.001). SOM divides K-means Cluster 1 into two categories. There is almost no difference in texture features between Cluster 3 and Cluster 4 in the SOM clustering results. Cluster 3's TB-L, TC-L, and Per-all are lower than Cluster 4 (P < 0.001), Cluster 3's TB-a, TC-a, TB-b, TC-b, and Per-part are higher than Cluster 4 (P < 0.001). Conclusions: The precise tongue image features calculated by TDAS are the basis for characterizing the disease state of diabetic people. Unsupervised learning technology combined with statistical analysis is an important means to discover subtle changes in the tongue features of diabetic people. The machine vision analysis method based on unsupervised machine learning technology realizes the classification of the diabetic population based on fine tongue features. It provides a diagnostic basis for the designated diabetes TCM treatment plan.

Study on Closely Related Citrus CMMs based on Chemometrics and Prediction of Components-Targets-Diseases Network by Ingenuity Pathway Analysis.

As the representatives of closely related Chinese medicinal materials (CMMs) originated from Rutaceae family, Aurantii fructus immaturus (AFI), Aurantii fructus (AF), Citri reticulatae pericarpium viride (CRPV), and Citri reticulatae pericarpium (CRP) have better functions in regulating qi and promoting gastrointestinal motility. However, differences in the quality of closely related Citrus CMMs have not yet been revealed until now. Herein, this study focused on the systematic differentiation and in-depth understanding of closely related Citrus CMMs by a strategy integrating chemometrics and network pharmacology. Determined by ultra performance liquid chromatography, the content of nine flavonoids showed obvious fluctuations in the decoction pieces from different species (Citrus aurantium Linnaeus and Citrus reticulate Blanco) with decreasing levels in the samples of ripe fruits. Decoction pieces from the different species and ripening stages were well distinguished by orthogonal projection to latent structure-discriminate analysis (OPLS-DA) and cluster analysis. As a result, four active components including narirutin, naringenin, hesperidin, and 3,5,6,7,8,3',4'-heptemthoxyflavone were filtered out by variable importance for the projection (VIP) value (VIP > 1.0), which were regarded as chemotaxonomic markers. Furthermore, a components-targets-diseases network was constructed via ingenuity pathway analysis (IPA), and the correlations were predicted between four chemotaxonomic markers, 223 targets, and three diseases including colitis, breast cancer, and colorectal cancer. The obtained results will be of great significance for identifying closely related Citrus CMMs and conduce to improving the resource utilization of CMMs.

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.

Protective effects of Ulva pertusa polysaccharide and polysaccharide­iron (III) complex on cyclophosphamide induced immunosuppression in mice.

A water-soluble polysaccharide was isolated from marine green algae Ulva pertusa and then chelated with iron to prepare the polysaccharide­iron (III) complex. The immunomodulatory activities of sulfated polysaccharide and polysaccharide­iron (III) complex were investigated through a mice immune-deficiency model. Cyclophosphamide (Cy) was utilized to establish mice immunodeficiency model. Both polysaccharide and polysaccharide­iron (III) complex were proved to promote the proliferation of lymphocyte and enhance the activities of mice macrophages. In mice serum, the levels of cytokines including TNF-α, IFN-γ and IL-10 restored and the contents of hemolysin were also found elevated after treatment with polysaccharide and its iron complex. Besides, it has been shown that both polysaccharide and polysaccharide­iron (III) complex increased the contents of Hb, RBC and HCT in mice blood, and the effect of iron complex was better. All these results suggested that Ulva pertusa polysaccharide could be developed as a healthy function food. It was also noteworthy that the polysaccharide­iron (III) complex showed no negative effect upon the immunomodulatory activity of polysaccharide. Instead, the polysaccharide­iron (III) complex showed excellent hematopoietic capacity perhaps due to the supplement of iron.

Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics.

The active compounds in Acanthopanax senticosus (AS) have different pharmacokinetic characteristics in mouse models. Cmax and AUC of Acanthopanax senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, due to the pathological state of ischemia and hypoxia, which are caused by radiation. In contrast, the ability of various metabolizing enzymes to inactivate, capacity of biofilm transport decrease, and lessening of renal blood flow accounts for radiation, resulting in the accumulation of syringin and eleutheroside E in the irradiated mouse. Therefore, there were higher pharmacokinetic parameters-AUC, MRT, and t1/2 of the two compounds in radiation-injured mouse, when compared with normal mouse. In order to investigate the intrinsic mechanism of AS on radiation injury, AS extract's protective effects on brain, the main part of mouse that suffered from radiation, were explored. The function of AS extract in repressing expression changes of radiation response proteins in prefrontal cortex (PFC) of mouse brain included tubulin protein family (α-, ß-tubulin subunits), dihydropyrimidinase-related protein 2 (CRMP2), γ-actin, 14-3-3 protein family (14-3-3ζ, ε), heat shock protein 90ß (HSP90ß), and enolase 2. The results demonstrated the AS extract had positive effects on nerve cells' structure, adhesion, locomotion, fission, and phagocytosis, through regulating various action pathways, such as Hippo, phagosome, PI3K/Akt (phosphatidylinositol 3 kinase/protein kinase B), Neurotrophin, Rap1 (Ras-related protein RAP-1A), gap junction glycolysis/gluconeogenesis, and HIF-1 (Hypoxia-inducible factor 1) signaling pathways to maintain normal mouse neurological activity. All of the results indicated that AS may be a promising alternative medicine for the treatment of radiation injury in mouse brain. It would be tested that whether the bioactive ingredients of AS could be effective through the blood-brain barrier in the future.

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.

Development and application of an UHPLC-MS method for comparative pharmacokinetic study of phenolic components from dragon's blood in rats under simulated microgravity environment.

Dragon's blood is a commonly used Chinese herbal medicine shown to have protective effects in simulated microgravity in rats and mice. The current study aimed to develop an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS) method for simultaneous determination of four phenolic components from the herb: loureirin A, loureirin C, 7,4'-dihydroxyflavone and pterostilbene in rats, and use the method for comparative study on the pharmacokinetics (PK) and excretion of these components in rats after oral dosage of dragon's blood under simulated microgravity environments. The results showed the developed UHPLC-MS method was sensitive and rapid. The comparative pharmacokinetic study in rats showed loureirin A, loureirin C and 7,4-dihydroxyflavone had decreased Cmax and AUC and increased Vd and CL in simulated microgravity environment; but pterostilbene had the opposite changes. The four phenolic components also showed increased or decreased excretions in simulated microgravity rats. These results indicate the chemical structure and physicochemical property, as well as physiological conditions may have an impact on the absorption and excretion of phenolic components in simulated microgravity environment. It also implies that different drug may behave differently in the same spaceflight condition leading to an increase or a reduction in pharmacodynamic outcomes.

Bone protection effects of a novel Chinese herbal formula, taikong yangxin prescription, in hindlimb unloaded rats against bone deterioration.

OBJECTIVE: To investigate the protective effects of a Chinese herbal formula, taikong yangxin prescription (TKYXP) against bone deterioration in a hindlimb unloaded (tail-suspension) rat model. METHODS: Thirty-two male Sprague-Dawley rats were divided into 4 groups: tail-suspension group fed with 2.5 g•kg(-1)•day(-1) of TKYXP extract (high dose), tail-suspension group fed with 1.25 g•kg(-1)•day(-1) (low dose), tail-suspended group treated with water placebo (placebo control group) and non tail-suspended group. The effects of TKYXP on bone were assessed using peripheral quantitative computed tomography (pQCT), microcomputerized tomography (micro-CT) and three-point bending biomechanical test on the femur in vivo. RESULTS: TKYXP had a significant protective effect against bone loss induced by tail-suspension on day 28, as shown in the reduction in bone mineral density (BMD) loss, preservation of bone micro-architecture and biomechanical strength. The administration ofhigh dose TKYXP could significantly reduce the total BMD loss by 4.8% and 8.0% at the femur and tibia regions, respectively, compared with the placebo control group (P<0.01) on day 28. Its bone protective effect on the femur was further substantiated by the increases of the trabecular BMD (by 6.6%), bone volume fraction (by 20.9%), trabecular number (by 9.5%) and thickness (by 11.9%) as compared with the placebo control group. CONCLUSION: TKYXP may protect the bone under weightless influence from gradual structural deterioration in the tail-suspension model.

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%.

Effect of Chinese herbal medicine on vascular functions during 60-day head-down bed rest.

PURPOSE: Chinese herbal medicine is a promising countermeasure against cardiovascular dysfunction associated with a sedentary lifestyle. We examined the impact of the Chinese herb, Taikong Yangxin, on the micro- and macrovascular dysfunction associated with a 60-day bed rest. METHODS: Fourteen healthy men were randomly divided into two groups: those given herbal supplement, and the control group; the two groups underwent a 60-day bed rest. The macrovasculature was assessed by sonography. Skin microvascular functions were assessed with laser Doppler. The plasma level of endothelial microparticles (EMPs), markers of endothelial injury, was determined. RESULTS: Bed rest induced a 33 % decrease in the femoral artery diameter and compliance whereas carotid wall thickness, diameter, and compliance remained unchanged. The early phase of endothelium-dependent vasodilation to ACh was unmodified by bed rest, while the late phase was reduced by 30 % along with a twofold increase in EMPs. In those given Taikong Yangxin, the early phase was amplified by 2.5-fold, and the effects of bed rest on the late phase were prevented. CONCLUSION: These findings indicate that Taikong Yangxin ameliorates endothelium-dependent vasodilation, likely by improving the NO pathway. The study suggests Taikong Yangxin as a new countermeasure to prevent the changes in microvascular function induced by physical inactivity.

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.

Simultaneous quantification of loureirin A and loureirin B in rat urine, feces, and bile by HPLC-MS/MS method and its application to excretion study.

A simple HPLC-MS/MS method for simultaneous determination of loureirin A and loureirin B in rat urine, feces, and bile after oral administration of 10.6 g/kg of longxuejie (one rare traditional Chinese medicinal herb) was developed for the first time. The analytes and buspirone (internal standard) were separated on a C(5) column with acetonitrile-water (containing 0.1% formic acid) as mobile phase at a flow rate of 0.4 min/mL. The detector was a Q-trap™ mass spectrometer with an electrospray ionization interface operating in the multiple reaction monitoring mode. Calibration curves of loureirin A in rat urine, feces, and bile were linear over the concentration range of 1.00-5,000 ng/mL. Loureirin B in rat urine, feces, and bile ranged between 0.08 and 20, 0.20 and 20, and 0.10 and 500 ng/mL, respectively. Validation revealed that the method was specific, accurate, and precise. The fully validated method was applied to the excretion study of loureirin A and loureirin B in rats. After oral administration of 10.6 g/kg longxuejie, cumulative excretion amount of loureirin A and loureirin B in rat urine were 2.94 ± 0.81 and 0.36 ± 0.16 µg at 72 h, respectively. Of the total dose, 5.35% of loureirin A and 5.46% of loureirin B were excreted from feces at 60 h. The cumulative amounts of loureirin A and loureirin B in rat bile reached 4.49 ± 0.98 and 5.11 ± 0.83 µg, respectively, at 36 h after dosing, accounting for 0.054% and 0.056% of the total dose.

Laser acupuncture and prevention of bone loss in tail-suspended rats.

BACKGROUND: Skeletal unloading during spaceflight results in bone loss. This study investigated whether laser acupuncture could be an effective countermeasure to prevent unloading-induced bone loss in rats. METHODS: There were 18 rats that were randomly assigned into three groups: a control group, a tail-suspended group (TS), and a tail-suspended with laser acupuncture treatment group (TSA). The rats in the TSA group were treated with laser acupuncture at the KI1 (Yong Quan) and ST36 (Zu San Li) acupoints of the left leg for 3 min per day. Bone mineral density (BMD), biomechanical properties, and histomorphometry of both tibiae were determined after the animals were euthanized at the end of week 4. RESULTS: Compared with the control group, BMD in the TS group significantly decreased by 12.3% in cortical bone and 15.1% in cancellous bone, whereas BMD in the TSA group decreased by only 3.1% in cortical bone and 9.0% in cancellous bone. The hardness of cortical bone dropped 44.1% in the TS group and 22.3% in the TSA group compared with the control group. The histomorphometry data were in accordance with BMD measurements. Although acupuncture treatment was applied only to the left side, we observed similar changes between the measurements of both the left and right tibiae. CONCLUSION: Laser acupuncture on KI1 and ST36 can inhibit bone loss in rats subjected to unloading. The fact that similar changes between the right and left sides when only the left limbs were treated suggests that the preventive effect of laser acupuncture occurs via a systemic regulation.

Chinese herbal medicine and cognitive and emotional functions during 60-day head-down bed rest.

INTRODUCTION: This study aimed to test the efficacy of an oral-intake Chinese herbal medicine in enhancing the cognitive and emotional functions of individuals in a simulated microgravity condition. The herbal medicine consisted of ingredients that may enhance cognitive and emotional functions in an extreme environment. METHODS: There were 14 healthy male subjects who were randomly assigned to a Chinese medicine (CMG) or a control (CG) group and underwent a 60-d 6 degree head-down bed-rest protocol. Testing was conducted before (Day -3), throughout (Days 3, 7, 20, 40, 57), and after (Days +3, +10) the bedrest protocol. The Arrow Test, Balloon Analog Risk Task (BART), Dual Task, and Affect Grid were administered on all testing days. RESULTS: The CMG demonstrated consistently higher scores on the BART (Days 20 to 40; Mean: CMG, 43.0 to 46.2 and CG, 30.2 to 25.5) and lower levels of arousal on the Affect Grid (Days 7 to 40; Mean: CMG, 6.9 to 6.7 and CG, 8.1 to 8.0) than did the CG. The CMG showed significantly higher performance on the Arrow Test (incompatible condition) at the beginning of the bed-rest period (Day 3 to 7; Mean: 799.5 ms and 763.1 ms, respectively) which was not observed in the CG. DISCUSSIONS: Results suggest that the Chinese herbal medicine may calm subjects' emotions by lowering the arousal level. At the same time, it may have produced positive effects in enhancing advantageous risk-taking and to a lesser extent self-regulatory behaviors (in the early phase).

Pygeum africanum: effect on oxidative stress in early diabetes-induced bladder.

OBJECTIVE: To evaluate the effect of Pygeum africanum on oxidative stress and functional changes of the bladder after diabetes induction. MATERIALS AND METHODS: Thirty-two adult Wistar male rats were treated daily for 8 weeks and grouped as follows: Control group (n = 6), Streptozotocin-induced diabetic group (n = 10), diabetes plus P. africanum group (n = 10), and control plus P. africanum group (n = 6). After diabetes induction for 4 weeks, the diabetes plus P. africanum and control plus P. africanum groups were fed with P. africanum (100 mg/kg, orally) in peanut oil for another 4 weeks. The catalase, superoxide dismutase activity, and malondialdehyde levels were measured as a marker of lipid peroxidation. The levels of inducible nitric oxide synthase were also evaluated. Urodynamic studies were performed to evaluate the functional changes of diabetic bladders after P. africanum treatment. RESULTS: The catalase and superoxide dismutase activities significantly increased (P < 0.05) and maleic dialdehyde levels significantly decreased from diabetic plus P. africanum group compared with diabetic group (P < 0.05). Immunohistochemical studies showed a significantly decreased number of inducible nitric oxide synthase-positive cells in diabetic plus P. africanum group compared with diabetic group (P < 0.05). In diabetic plus P. africanum group, maximal bladder volume significantly decreased, while bladder pressure and maximal bladder pressure significantly increased compared with diabetic group (P < 0.05). CONCLUSIONS: Early treatment with P. africanum could effectively suppress the oxidative stress status in diabetic bladder and may slow down the process of diabetic cystopathy.

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.