Analysis of high-dimensional metabolomics data with complex temporal dynamics using RM-ASCA.

The intricate dependency structure of biological "omics" data, particularly those originating from longitudinal intervention studies with frequently sampled repeated measurements renders the analysis of such data challenging. The high-dimensionality, inter-relatedness of multiple outcomes, and heterogeneity in the studied systems all add to the difficulty in deriving meaningful information. In addition, the subtle differences in dynamics often deemed meaningful in nutritional intervention studies can be particularly challenging to quantify. In this work we demonstrate the use of quantitative longitudinal models within the repeated-measures ANOVA simultaneous component analysis+ (RM-ASCA+) framework to capture the dynamics in frequently sampled longitudinal data with multivariate outcomes. We illustrate the use of linear mixed models with polynomial and spline basis expansion of the time variable within RM-ASCA+ in order to quantify non-linear dynamics in a simulation study as well as in a metabolomics data set. We show that the proposed approach presents a convenient and interpretable way to systematically quantify and summarize multivariate outcomes in longitudinal studies while accounting for proper within subject dependency structures.

In vivo non-contact regions of proximal scaphoid in six extreme wrist positions.

INTRODUCTION: Fractures of the scaphoid are the most common carpal injuries, account for 80-90% of all carpal fractures. 5-15% nonunion of scaphoid fractures were reported even with adequate primary treatment, which probably progresses to osteoarthritic changes several decades later. Researches regarding to scaphoid physiological characteristic in vitro and in vivo and kinds of trials in clinical practice are being kept on going, which contribute much to our clinical practice. With the advancing wrist arthroscopy, 3D-print patient-specific drill guide, and intraoperative fluoroscopic guidance, dorsal approach (mini-invasive and percutaneous technique) is being popular, through which we can implant the screw in good coincidence with biomechanics and with less disturbing tenuous blood supply of the scaphoid. Investigating the noncontact area of the dorsal proximal scaphoid in different wrist positions can facilitate preoperatively estimating insert point of the screw. MATERIALS AND METHODS: Eight volunteers were recruited to accept CT scans in six extreme wrist positions. The images of DICOM mode were imput into the Mimics analytical system, the segmented scaphoid, lunate and radius were exported in mode of ASCII STL and were opened in the software of Geomagic studio. We created four planes based on anatomic markers on the surface of the radius and scaphoid to confine the proximal scaphoid to form the so-called non-contact regions. We measured and compared the areas in six targeted positions. RESULTS: Amidst six extreme wrist positions, area of the non-contact region in extreme dorsal extension (59.81 ± 26.46 mm2) was significantly the smallest, and it in extreme palmar flexion significantly was largest (170.51 ± 30.44 mm2). The non-contact regions increased in order of dorsal extension, supination, ulnar deviation, radial deviation, pronation and palmar flexion. As for two-group comparison, the non-contact region showed significantly larger (p < 0.05) in palmar flexion than the others except for in pronation individually, and in radial deviation (p < 0.05) than in dorsal extension. CONCLUSIONS: Sufficient space was available for the screw started from the dorsal approach despite the wrist positions.

Synthesis and biological evaluation of novel 8- substituted sampangine derivatives as potent inhibitor of Zn2+-Aß complex mediated toxicity, oxidative stress and inflammation.

A series of 8-substituted sampangine derivatives have been designed, synthesized and tested for their ability to inhibit cholinesterase and penetrate the blood-brain barrier. Their chelating ability toward Zn2+ and other biologically relevant metal ions was also demonstrated by isothermal titration calorimetry. The new derivatives exhibited high acetylcholinesterase inhibitory activity, high blood-brain barrier penetration ability and high chelating selectivity for Zn2+. Moreover, compound 10 with the strongest binding affinity to Zn2+ was selected for further research. Western blotting analysis, transmission electron microscopy, DCFH-DA assay and paralysis experiment indicated that compound 10 suppressed the formation of Zn2+-Aß complexes, alleviated the Zn2+ induced neurotoxicity and inhibited the production of ROS catalyzed by Zn2+ in Aß42 transgenic C. elegans. Furthermore, compound 10 also inhibited the expressions of pro-inflammatory cytokines, such as NO, TNF-α, IL-6 and IL-1ß, induced by Zn2+ + Aß1-42 in BV2 microglial cells. In general, this work provided new insights into the design and development of potent metal-chelating agents for Alzheimer's disease treatment.

N-terminal domain of EcC1INH in Epinephelus coioides can antagonize the LPS-stimulated inflammatory response.

Complement 1 inhibitor (C1INH) serving as a multifunctional factor can participate in the regulation of complement cascades and attenuate the activation of various proteases. In this study, we obtained EcC1INH cDNA and the tissue-specific analysis indicate that the highest expression level of EcC1INH mRNA was detected in liver. Moreover, Vibrio alginolyticus challenge can significantly increase EcC1INH mRNA expression in liver and kidney. N-terminal domain of EcC1INH could decrease LPS binding activity to cell surface, while loss of positively charged residues (PCRs) Arg21, His22, Lys50, Arg61 in N-terminal domain of EcC1INH can significantly reduce its interaction with LPS. Furthermore, LPS injection experiment indicated that the binding of EcC1INH N-terminal domain to LPS can antagonize LPS-induced inflammatory signaling pathway and attenuate the production of proinflammatory cytokines in vivo, indicating that EcC1INH was involved in negative regulation of inflammatory response.

Synthesis and enhanced microwave absorption properties: a strongly hydrogenated TiO2 nanomaterial.

Due to its improved physical and chemical performances, a strongly hydrogenated TiO2 was designed and produced successfully by using a sealing-transfer reduction method at a relatively low temperature (425 °C). The microstructures, electromagnetic and microwave absorbing properties were investigated in detail. Experimental results revealed that: (1) the minimum reflection loss (RL) value of the hydrogenated TiO2 up to -53.8 dB (99.999 99% of EM wave attenuation) was reached at 11.2 GHz, and the RL values below -20 dB (99%) were obtained in a frequency range of 7.3-16.8 GHz. (2) Compared to pristine TiO2 and black TiO2 in other reports, the present hydrogenated TiO2 exhibited greatly improved microwave absorption performance. Moreover, the mechanism was also discussed. It was demonstrated that the excellent microwave absorption performance of the black TiO2 arose from the strong dielectric loss, excellent impedance matching and attention loss due to associated relaxation and interfacial polarization. It is expected that the hydrogenated TiO2 exhibits great potential applications in the area of high performance microwave absorbing materials. In addition, it is believed that the black TiO2 @ magnetic metals composites will display an excellent microwave absorbing property.

Molecular cloning and characterization of PTEN in the orange-spotted grouper (Epinephelus coioides).

PTEN is a key tumor suppressor gene that can play a regulatory role in the cellular proliferation, survival and apoptosis. In this study, the full-length PTEN (EcPTEN) was obtained, containing a 5'UTR of 745 bp, an ORF of 1269 bp and a 3'UTR of 106 bp. The EcPTEN gene encoded a polypeptide of 422 amino acids with an estimated molecular mass of 49.14 KDa and a predicted isoelectric point (pI) of 6.34. The deduced amino acid sequence analysis showed that EcPTEN comprised the conserved residues and the characteristic domains known to the critical functionality of PTEN. qRT-PCR analysis revealed that EcPTEN mRNA was broadly expressed in all the examined tissues, while the highest expression level was observed in liver, followed by the expression in blood, kidney, spleen, heart, gill, muscle and intestine. The groupers challenged with Vibrio alginolyticus showed a sharp increase of EcPTEN mRNA expression in immune tissues. In addition, western blotting analysis confirmed that the up-regulation of EcPTEN protein expression was steadily induced in liver. Subcellular localization analysis indicated that EcPTEN was localized in both nucleus and cytoplasm. Overexpression of EcPTEN can activate the apoptotic cascade and abrogate NF-kB, AP-1, Stat3 and Myc promoter activity in Hela cells. These results indicated that EcPTEN harboring highly-conserved domains with a close sequence similarity to those of PTP superfamily may disrupt the mammalian signalings and play a regulatory role in the apoptotic process.

In Vivo Contact Characteristics of Distal Radioulnar Joint With Malunited Distal Radius During Wrist Motion.

PURPOSE: To determine whether distal radioulnar joint (DRUJ) contact characteristics were altered in patients with malunited distal radius fractures. METHODS: We obtained computed tomography scans at 5 positions of both wrists of 6 patients who had unilateral malunited distal radius fractures with dorsal angulation from 10° to 20° and ulnar variance less than 3 mm. We reconstructed 3-dimensional images and mapped contact regions of DRUJ by calculating the shortest distance between the 2 opposing bones. The contact areas of the DRUJ were measured and the contact region centers were calculated and analyzed. The values of the malunited side were compared with those of the contralateral uninjured side. RESULTS: In the uninjured wrist, the contact areas of the DRUJ increased slightly from wrist flexion to extension and ulnar deviation. In the malunited wrist, we found the contact areas of DRUJ to be progressively reduced from 20° flexion to neutral, 40° extension, and 20° extension, to ulnar deviation. The centroid of this area on the sigmoid notch moved to distal from flexion to extension. Compared with the contralateral uninjured wrist, the contact area significantly decreased during wrist extension and ulnar deviation, and significantly increased during wrist flexion. The centroids of this area on sigmoid notch all moved volarly in all selected wrist positions. CONCLUSIONS: The contact areas of the DRUJ and the centroid of contact area on sigmoid notch are altered in patients with malunited distal radius fractures. The contact area of the DRUJ increases during wrist flexion and decreases during wrist extension and ulnar deviation. The centroids of the contact area on sigmoid notch move volarly during wrist flexion-extension and ulnar deviation. CLINICAL RELEVANCE: The in vivo findings suggest that alterations in joint mechanics may have an important role in the dysfunction associated with these injuries.

Enhancing the Repair of Substantial Volumetric Muscle Loss by Creating Different Levels of Blood Vessel Networks Using Pre-Vascularized Nerve Hydrogel Implants.

Volumetric muscle loss (VML), a severe muscle tissue loss from trauma or surgery, results in scarring, limited regeneration, and significant fibrosis, leading to lasting reductions in muscle mass and function. A promising approach for VML recovery involves restoring vascular and neural networks at the injury site, a process not extensively studied yet. Collagen hydrogels have been investigated as scaffolds for blood vessel formation due to their biocompatibility, but reconstructing blood vessels and guiding innervation at the injury site is still difficult. In this study, collagen hydrogels with varied densities of vessel-forming cells are implanted subcutaneously in mice, generating pre-vascularized hydrogels with diverse vessel densities (0-145 numbers/mm2) within a week. These hydrogels, after being transplanted into muscle injury sites, are assessed for muscle repair capabilities. Results showed that hydrogels with high microvessel densities, filling the wound area, effectively reconnected with host vasculature and neural networks, promoting neovascularization and muscle integration, and addressing about 63% of the VML.

Flower-like NiO to flower-like NiO/Ni@C microspheres: An effective strategy to comprehensively improve the loss capabilities.

It was well recognized that the penetrated electromagnetic (EM) wave could be dissipated by means of magnetic loss, polarization loss and conduction loss. In order to improve their loss capacities and take full advantage of flower-like geometrical morphology, in this study, we proposed a simple route for the production of flower-like core@shell structure NiO/Ni@C microspheres through the carbon thermal reaction using NiO microflowers as precursor. The obtained results revealed that our proposed strategy successfully synthesized the core@shell structure magnetic carbon-based multicomponent nanocomposites without destroying the geometrical morphology of precursor. By regulating the annealing temperature, the as-prepared NiO/Ni@C microspheres with different contents of Ni and degrees of graphitization could be selectively synthesized, which effectively boosted their magnetic loss, polarization loss and conduction loss capabilities. Therefore, the elaborately designed NiO/Ni@C microspheres displayed the superior microwave absorption performances including strong absorption capability, broad absorption bandwidth and thin matching thicknesses compared to the NiO precursor. In summary, our findings not only provided a simple route to design and synthesize flower-like core@shell structure magnetic carbon-based nanocomposites as novel microwave absorbers, but also presented an effective strategy to comprehensively improve their loss capacities.

Engineering large and geometrically controlled vascularized nerve tissue in collagen hydrogels to restore large-sized volumetric muscle loss.

Developing scalable vascularized and innervated tissue is a critical challenge for the successful clinical application of tissue-engineered constructs. Collagen hydrogels are extensively utilized in cell-mediated vascular network formation because of their naturally excellent biological properties. However, the substantial increase in hydrogel contraction induced by populated cells limits their long-term use. Previous studies attempted to mitigate this issue by concentrating collagen pre-polymer solutions or synthesizing covalently crosslinked collagen hydrogels. However, these methods only partially reduce hydrogel contraction while hindering blood vessel formation within the hydrogels. To address this challenge, we introduced additional support in the form of a supportive spacer to counteract the contraction forces of populated cells and prevent hydrogel contraction. This approach was found to promote cell spreading, resist hydrogel contraction, control hydrogel/tissue geometry, and even facilitate the engineering of functional blood vessels and host nerve growth in just one week. Subsequently, implanting these engineered tissues into muscle defect sites resulted in timely anastomosis with the host vasculature, leading to enhanced myogenesis, increased muscle innervation, and the restoration of injured muscle functionality. Overall, this innovative strategy expands the applicability of collagen hydrogels in fabricating large vascularized nerve tissue constructs for repairing volumetric muscle loss (∼63 %) and restoring muscle function.

Synthesis and structure-activity relationships of imidazo[1,2-a]pyrimidin-5(1H)-ones as a novel series of beta isoform selective phosphatidylinositol 3-kinase inhibitors.

A series of PI3K-beta selective inhibitors, imidazo[1,2-a]-pyrimidin-5(1H)-ones, has been rationally designed based on the docking model of the more potent R enantiomer of TGX-221, identified by a chiral separation, in a PI3K-beta homology model. Synthesis and SAR of this novel chemotype are described. Several compounds in the series demonstrated potent growth inhibition in a PTEN-deficient breast cancer cell line MDA-MB-468 under anchorage independent conditions.

[Effects of qi-supplementing dominated Chinese materia medica combined with rehabilitation training on the quality of life of ischemic post-stroke fatigue patients of qi deficiency syndrome].

OBJECTIVE: To observe the effects of qi-supplementing dominated Chinese materia medica (QSDCMM) combined with rehabilitation training on the quality of life (QOL) of ischemic post-stroke fatigue (PSF) patients of qi deficiency syndrome. METHODS: Ninety ischemic stroke patients of qi deficiency were randomly assigned to 3 groups, 30 in each. Patients in the Chinese medicine treatment group were treated with oral administration of QSDCMM decoction and rehabilitation. Those in the Western medicine treatment group were treated with Chinese medicine placebo, Western medicine, and rehabilitation. Those in the control group were treated with Chinese medicine placebo and rehabilitation. The therapeutic course for all was 4 weeks. All patients were assessed using Stroke Specific Quality of Life Scale (SS-QOL) and Fatigue Severity Scale (FSS) before treatment and 4 weeks after treatment. RESULTS: After treatment the scores of SS-QOL and FSS increased in the 3 groups, especially in the CM treatment group, showing significant difference (P < 0.05). After treatment significant difference existed between the CM treatment group and the Western medicine treatment group, between the CM treatment group and the control group, showing significant difference (P < 0.05). There was no statistical difference between the Western medicine treatment group and the control group (P > 0.05). CONCLUSION: QSDCMM combined with rehabilitation training could improve the QOL of ischemic PSF patients of qi deficiency syndrome.

Constructing MoSe2/MoS2 and MoS2/MoSe2 inner and outer-interchangeable flower-like heterojunctions: A combined strategy of interface polarization and morphology configuration to optimize microwave absorption performance.

Interfacial polarization and geometrical morphology play a significant role in the attenuation of electromagnetic (EM) wave. Herein, the two-dimensional (2D)/2D heterojunction with flower-like geometrical morphology is proposed and produced, which may simultaneously provide a large contact area for achieving strong interfacial polarization and activates more sites for the possible multiple EM wave reflection and scattering. By adopting a simple two-step hydrothermal method, MoSe2/MoS2and MoS2/MoSe2 inner and outer-interchangeable heterojunctions consisting of 2D MoSe2 and MoS2 nanosheets with flower-like geometrical morphology were successfully synthesized. The results revealed that the hydrothermal temperatures significantly impacted the flower-like geometrical morphology and MoS2 content. By optimizing the microstructures, the designed MoSe2/MoS2 and MoS2/MoSe2 heterojunctions presented enhanced comprehensive EM wave absorption properties (EMWAPs), possessing strong absorption capability, wide absorption bandwidth and thin matching thicknesses. Generally, this work demonstrates that the optimized EMWAPs of designed heterojunctions mainly originate from the special interfaces and morphology configuration, which also paves a new way for the designing and synthesis of transition metal dichalcogenides-based heterojunction as a novel and desirable candidate for high-performance microwave absorbers.

Magnetic modulation of core@shell MoS2-based flower-like multicomponent nanocomposites to improve microwave attenuation.

Nanocomposites with a three-dimensional (3D) flower-like geometrical morphology were considered as excellent microwave absorbers (MAs) because of the numerous effective sites for the multiple reflections of electromagnetic (EM) wave. Herein, for optimizing the EM matching characteristic and taking full advantage of interface polarization, a strategy of magnetic modulation was proposed to further improve the EM wave absorption performances (EMWAPs) of MoS2-based nanocomposites. We adopted a simple hydrothermal route and a combined method of hydrothermal treatment/hydrogen reduction to synthesize core@shell CoFe2O4@MoS2 and CoFe@MoO2/MoS2 flower-like nanocomposites, respectively. The obtained results indicated that the hydrogen reduction effectively improved their magnetic properties and magnetic loss capabilities, and their 3D flower-like geometrical morphologies were well maintained during the hydrogen reduction process. The obtained core@shell CoFe@MoO2/MoS2 flower-like nanocomposites presented the extraordinary comprehensive EMWAPs including the optimal reflection loss value of -54.83 dB with the matching thicknesses (dm) value of 2.05 mm and effective absorption bandwidth value of 6.40 GHz with the dm value of 2.59 mm, which were evidently superior to the properties of CoFe2O4@MoS2. Therefore, the findings provided an effective pathway to further improve EMWAPs of MoS2-based core@shell nanocomposites and the as-prepared core@shell CoFe@MoO2/MoS2 flower-like nanocomposites could be utilized as the novel high-efficient MAs.

Investigation of the role of the autophagic protein LC3B in the regulation of human airway epithelium cell differentiation in COPD using a biomimetic model.

Chronic obstructive pulmonary disease (COPD) is one of the most lethal chronic disease worldwide; however, the establishment of reliable in vitro models for exploring the biological mechanisms of COPD remains challenging. Here, we determined the differences in the expression and characteristics of the autophagic protein LC3B in normal and COPD human small airway epithelial cells and found that the nucleus of COPD cells obviously accumulated LC3B. We next established 3D human small airway tissues with distinct disease characteristics by regulating the biological microenvironment, extracellular matrix, and air-liquid interface culture methods. Using this biomimetic model, we found that LC3B affects the differentiation of COPD cells into basal, secretory, mucous, and ciliated cells. Moreover, although chloroquine and ivermectin effectively inhibited the expression of LC3B in the nucleus, chloroquine specifically maintained the performance of LC3B in cytoplasm, thereby contributing to the differentiation of ciliated cells and subsequent improvement in the beating functions of the cilia, whereas ivermectin only facilitated differentiation of goblet cells. We demonstrated that the autophagic mechanism of LC3B in the nucleus is one factor regulating the ciliary differentiation and function of COPD cells. Our innovative model can be used to further analyze the physiological mechanisms in the in vitro airway environment.

Effect of total glycosides from Eucommia ulmoides seed on bone microarchitecture in rats.

Du-Zhong is one of the most important tonic herbs in traditional Chinese medicine for the treatment of bone fractures and other bone diseases. The present study examined whether Du-Zhong seed extract named total glycosides from Eucommia ulmoides seed (TGEUS) could display an increased effect on bone density and bone strength of the femur in rats. Sprague-Dawley rats were used and randomly assigned to the normal group and the TGEUS group (400 mg/kg body weight/day). Daily oral administration of TGEUS was found to increase significantly the biomechanical quality of the femur. The mechanical changes were associated with a bone mineral density (BMD) increase or even with some improvements in microarchitecture. Micro-CT analysis of the distal femur showed that TGEUS significantly increased the bone volume/tissue volume (BV/TV), connectivity density (Conn.D), trabecular number (Tb.N) and trabecular thickness (Tb.Th), and decreased trabecular separation (Tb.Sp) and the structure model index (SMI) in normal rats. To conclude, TGEUS taken orally increased bone density and altered bone histomorphology, suggesting that TGEUS might be a potential alternative medicine for the treatment of postmenopausal osteoporosis.

Scaphoid and lunate movement in different ranges of carpal radioulnar deviation.

PURPOSE: We aimed to investigate scaphoid and lunate movement in radial deviation and in slight and moderate ulnar deviation ranges in vivo. METHODS: We obtained computed tomography scans of the right wrists from 20° radial deviation to 40° ulnar deviation in 20° increments in 6 volunteers. The 3-dimensional bony structures of the wrist, including the distal radius and ulna, were reconstructed with customized software. The changes in position of the scaphoid and lunate along flexion-extension motion (FEM), radioulnar deviation (RUD), and supination-pronation axes in 3 parts--radial deviation and slight and moderate ulnar deviation--of the carpal RUD were calculated and analyzed. RESULTS: During carpal RUD, scaphoid and lunate motion along 3 axes--FEM, RUD, and supination-pronation--were the greatest in the middle third of the measured RUD (from neutral position to 20° ulnar deviation) and the smallest in radial deviation. Scaphoid motion along the FEM, RUD, and supination-pronation axes in the middle third was about half that in the entire motion range. In the middle motion range, lunate movement along the FEM and RUD axes was also the greatest. CONCLUSIONS: During carpal RUD, the greatest scaphoid and lunate movement occurs in the middle of the arc--slight ulnar deviation--which the wrist frequently adopts to accomplish major hand actions. At radial deviation, scaphoid and lunate motion is the smallest.

In vivo length and changes of ligaments stabilizing the thumb carpometacarpal joint.

PURPOSE: To investigate the lengths and changes of selected ligaments stabilizing the thumb carpometacarpal (CMC) joint during thumb motion in vivo. METHODS: We obtained serial computed tomography scans of the thumb CMC joints of 6 healthy volunteers during thumb flexion, abduction, and opposition. We reconstructed the 3-dimensional structures of the bones of the thumb CMC joint using customized software and modeled the paths of fibers of 5 principal ligaments--deep anterior oblique (beak), dorsoradial, posterior oblique, intermetacarpal, and dorsal intermetacarpal--at each of the CMC joint positions studied. We estimated the virtual lengths of these ligaments in neutral position, flexion, abduction, and opposition of the CMC joint by measuring the distances between the origin and the insertion of individual ligaments, and statistically analyzed the length changes. RESULTS: The estimated length of the CMC joint ligaments underwent significant changes during thumb motion in vivo. Thumb flexion led to the greatest changes in ligament lengths. During flexion, all the ligaments lengthened significantly (p < .05 or p < .01), except for the beak ligament, which shortened significantly (p < .001). The lengths of the ligaments changed similarly during thumb abduction and opposition, except for the dorsoradial ligament. In both motions, the posterior oblique and dorsal intermetacarpal ligaments lengthened and the beak ligament shortened significantly (p < .05 or p < .01). During the 3 thumb motions, the beak ligament underwent marked shortening, while the other measured ligaments lengthened to varied extent. CONCLUSIONS: The estimated lengths of principal ligaments stabilizing the CMC joint change substantially during thumb motions in vivo. Thumb flexion causes the greatest changes of the ligament lengths; abduction and opposition result in similar changes in the ligament lengths. The beak ligaments shorten while the other ligaments lengthen. This in vivo study suggests that thumb motions expose the CMC joint ligaments to different tensions at these thumb positions, and that the ligaments are under lower tension during thumb opposition and abduction than during flexion.

[Effects of integrative medicine protocols on the improvement of neural function deficit and disability outcomes in patients with acute ischemic cerebral stroke].

OBJECTIVE: To study the effects of integrative medicine protocols on the neural function deficit and short-term disability outcomes in patients with acute ischemic cerebral stroke. METHODS: 99 patients were randomly assigned to three groups, i.e., the Dengzhan Xixin (fleabane) group (Group A), the Kudiezi (sowthistle-leaf ixeris seedling) group (Group B), and the Western medicine control group (Group C). Dengzhan Xixin Injection was intravenously dripped to patients in Group A for 14 days. Chinese decoction was administered to them by pattern typing as well. Meanwhile, they took Dengzhan Shengmai Capsule for two months. Kudiezi Injection was intravenously dripped to patients in Group B for 14 days. Chinese decoction was administered to them by pattern typing as well. Meanwhile, they took Naoshuantong Capsule for two months. In addition to internal therapies, patients in Group A and B received acupuncture, massage, and external washing with Chinese medicine for 21 days. Patients in Group C also received modem rehabilitation therapy for 21 days, including rehabilitation training and electronic stimulus in addition to the internal medicine. The National Institute of Health Stroke Scale (NIHSS) and disability outcome (modified Rank Scale, mRS) were taken as main effect indices. RESULTS: The NIHSS scores at each time point obviously decreased more than before treatment in all the three groups (P<0.01), but with no difference at each time point (P>0.05). The disability outcomes of all the three groups postponed as time went by. Significant difference existed among the three groups by log-lineal model (CATMOD) (P<0.05). The best effect was shown in Group B, with the markedly effective rate of 19. 35% and the total effective rate 54.84%. CONCLUSIONS: The integrative medicine protocols could improve the nerve functions of ischemic stroke patients. Therefore, it could improve the disability outcomes. The comprehensive protocol (Kudiezi Injection + Naoshuantong Capsule + Chinese decoction according to pattern typing + acupuncture + massage + external washing with Chinese medicine) was better.