Recovery of Volitional Motor Control and Overground Walking in Participants With Chronic Clinically Motor Complete Spinal Cord Injury: Restoration of Rehabilitative Function With Epidural Spinal Stimulation (RESTORES) Trial-A Preliminary Study.

Spinal cord injury (SCI) is damage to any part of the spinal cord resulting in paralysis, bowel and/or bladder incontinence, and loss of sensation and other bodily functions. Current treatments for chronic SCI are focused on managing symptoms and preventing further damage to the spinal cord with limited neuro-restorative interventions. Recent research and independent clinical trials of spinal cord stimulation (SCS) or intensive neuro-rehabilitation including neuro-robotics in participants with SCI have suggested potential malleability of the neuronal networks for neurological recovery. We hypothesize that epidural electrical stimulation (EES) delivered via SCS in conjunction with mental imagery practice and robotic neuro-rehabilitation can synergistically improve volitional motor function below the level of injury in participants with chronic clinically motor-complete SCI. In our pilot clinical RESTORES trial (RESToration Of Rehabilitative function with Epidural spinal Stimulation), we investigate the feasibility of this combined multi-modal approach in restoring volitional motor control and achieving independent overground locomotion in participants with chronic motor complete thoracic SCI. Secondary aims are to assess the safety of this combination therapy including the off-label SCS usage as well as improving functional outcome measures. To our knowledge, this is the first clinical trial that investigates the combined impact of this multi-modal EES and rehabilitation strategy in participants with chronic motor complete SCI. Two participants with chronic motor-complete thoracic SCI were recruited for this pilot trial. Both participants have successfully regained volitional motor control below their level of SCI injury and achieved independent overground walking within a month of post-operative stimulation and rehabilitation. There were no adverse events noted in our trial and there was an improvement in post-operative truncal stability score. Results from this pilot study demonstrates the feasibility of combining EES, mental imagery practice and robotic rehabilitation in improving volitional motor control below level of SCI injury and restoring independent overground walking for participants with chronic motor-complete SCI. Our team believes that this provides very exciting promise in a field currently devoid of disease-modifying therapies.

[Active components and mechanism of Jinwugutong Capsules in treatment of osteoporosis: a study based on UPLC-Q-Exactive-MS/MS combined with network pharmacology].

UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the "drug-component-target-pathway-disease" network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.

Novel third-generation tyrosine kinase inhibitor for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a case study.

Although Philadelphia chromosome-positive acute leukemia (Ph + -ALL) has been revolutionized with tyrosine kinase inhibitors (TKIs), resistance and mutation are universal events during treatment with first-generation and second-generation TKIs. The present third-generation TKI has a dose-dependent, increased risk of serious cardiovascular events and the sensitivity is poor for patients with ≥2 mutations accompanied by the T315I mutation. Thus, novel and well-tolerated TKIs should be explored. This study analyzes the efficacy and advert effects of olverembatinib, a novel third TKI, in the treatment of newly diagnosed adult Ph + -ALL in induction therapy. Four adult patients with newly diagnosed Ph + -ALL were treated with olverembatinib as the first-line treatment. For induction therapy, these patients received 40 mg of oral olverembatinib quaque omni die for 28 days, 1 mg/kg/d of prednisone for 14 days, then tapered and stopped at 28 days and vindesine 4 mg/d at days 1, 8 and 15. After induction therapy, these patients received median or high-dose of cytarabine and methotrexate combined with oral olverembatinib as consolidation therapy. Then the allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed. All patients reached complete remission with a complete cytogenetic response after induction therapy. Two patients reached major molecular remission and one with complete molecular remission. Before allo-HSCT, all the patients achieved complete molecular remission. All the patients have survived disease-free for 3-6 months. No severe advert effects were observed. It is well-tolerated and effective for olverembatinib in the treatment of newly diagnosed adult patients with Ph + -ALL. A prospective study should be performed to further testify the role.

Visualizing the spatial distribution of metabolites in Clausena lansium (Lour.) skeels using matrix-assisted laser desorption/ionization mass spectrometry imaging.

Clausena lansium (Lour.) Skeels (Rutaceae) is a natural bioactive plant. Its roots, stems, leaves, and seeds are widely used in Chinese traditional and folk medicine. Although the characterization and functional analysis of bioactive components in Clausena lansium (Lour.) Skeels has been widely reported, the spatial distribution of these compounds within the main plant tissues remains undefined. Here, we adopted matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to reveal the spatial distribution of active alkaloids, coumarins, sugars and organic acids in C. lansium. Using a combined wet and dry matrix covering method to enhance sensitivity, we detected alkaloids throughout the fruit including 3-methylcarbazole and murrastinine which were especially rich in the kernel tissues but were restricted to the stem xylem and medulla and in the leaf epidermal region. Interestingly, murrayanine and heptaphylline were mainly found in pulp tissues with very low content in the stems and leaves while girinimbine was only distributed within the outer kernel skin. Coumarins were mainly distributed in the fruit pericarp and leaf vein tissues but with no clear spatial specificity in stems. Lastly, hexoses were mainly evident in the fruit pulp, although sucrose was also found in the pericarp, pulp, and pulp fibers with citric acid being distributed throughout the fruit. The accurate spatial and chemical information obtained provides new insights into the specific accumulation of metabolites in individual tissues.

[Rapid determination of the multi-marker ingredients in Heterosmilacis Japonicae Rhizoma and Sophorae Flavescentis Radix with near-infrared diffused reflection spectroscopy].

A rapid NIRS method for determination of macrozamin in Heterosmilacis japonicae rhizoma (HJR), and the total content of oxymatrine and matrine (OMT + MT) as well as the total content of oxysophocarpine and sophocarpine (OSC + SC) in sophorae flavescens radix (SFR) was developed to explore the application feasibility of NIRS for the quality assurance system of Chinese patent drugs. The contents of macrozamin in HJR samples, and OMT + MT and OSC + SC in SFR samples were determined by HPLC as reference values. The NIR spectra of the samples were measured in a diffused reflection mode. The different characteristic wavebands and pretreatment methods were optimized. The quantitative calibration models between the NIR spectra and the content reference values of marker components in HJR and SFR samples, were established with partial least square method, and further optimized through the cross validation and external validation. The contents of macrozamin in 88 batches of HJR samples were over the range of 0.36-12.88 mg · g(-1). The total contents of OMT + MT and OSC + SC in 75 batches of SFR samples were over the range of 8.87-66.31 and 2.30-15.11 mg · g(-1), respectively. The performance of the final models for macrozamin, OMT + MT and OSC + SC was evaluated well according to correlation coefficients (r), root mean square error of cross-validation (RMSECV) and root mean square error of prediction (RMSEP). The R2 values of the cross-validation for macrozamin, OMT + MT and OSC + SC were 0.9025, 0.9491 and 0.9137, and those of RMSECV were 0.961, 2.45 and 0.724 mg · g(-1) respectively. The R2 values of external validation for the three models were 0.9817, 0.9826 and 0.9609, and those of RMSEP were 0.693, 2.27 and 0.658 mg · g(-1), respectively. This is the first report on rapid determination of macrozamin in Heterosmilacis japonicae rhizoma, and oxymatrine, matrine, oxysophocarpine and sophocarpine in sophorae flavescens radix by NIRS method. The presented method can fulfill the requirement of rapid acquirement of chemical information of raw medicinal materials prior the manufacturing of compound Kushen injection.

[Assessment of soil nutrient status in urban green space of main cities in Hubei Province, China].

According to the topography of the cities in Hubei Province, soil samples were collected from the urban green space in two mountainous cities (Enshi and Shiyan), three hilly cities (Jing-men, Xiangfan and Yichang), and five plain cities (Wuhan, Xiaogan, Xianning, Jingzhou, Suizhou and Huangshi). Within each city, subsoil samples were taken in accordance with four different types of land use, including park, residential, institutional (school, hospital and government, etc.), and roadside. In the main cities in Hubei, the soil pH of urban green space was averagely 7.9, being obviously higher than that of natural soils, while the soil organic matter content was rather low (6.8 g x kg(-1)). The soil available N and P contents were at a low level, while the soil available trace element (Ca, Mg, S, Fe, Cu, Mn, Zn and B) contents were moderate. Land use type had significant effects on the soil nutrient contents in plain cities. The soil pH in the residential green space was significantly higher than that in the park, roadside and institutional green space, while the contents of soil available trace elements (S, Cu, Mn and Zn) in roadside green space were significantly higher than those of green space in the other land use types. Park green space had the lowest soil nutrient contents. There existed significant differences in the soil nutrient contents among the cities with different topography. The soil organic matter, NH4-N, available K and P, and Ca, Mg, S, Fe, Cu and Mn contents were significantly higher in plain cities than in mountainous cities.