Objective To explore the potential mechanisms of hypoxic adaptive metabolic changes in the kidneys of plateau pikas at different altitudes using non-targeted metabolomics analysis via ultra-high-performance liquid chromatography coupled with quadrupole electrostatic field orbital trap-mass spectrometry (UHPLC-QE-MS). Methods 10 plateau pikas were captured at an altitude of 4 360 m in Xingxiuhai area, Maduo County, Guoluo Tibetan Autonomous Prefecture, Qinghai Province (MD group), and 10 plateau pikas were captured at an altitude of 2 900 m in Menyuan area, Haibei Tibetan Autonomous Prefecture, Qinghai Province (MY group). After anesthesia, serum samples were collected, and kidney samples were collected after euthanasia. General physiological and biochemical indicators were measured and metabolomics analysis was performed. Part of the serum samples was used for hematology analysis, another part for blood gas analysis, and the remaining part for biochemical indicator detection. Metabolites were extracted from the kidney tissue samples and then analyzed using UHPLC-QE-MS. Differential metabolites were analyzed using metabolomics principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), with screening criteria set as variable importance in projection (VIP)>1.5 and fold change (FC)>1.5, or VIP>1.5 and FC<1/1.5. Correlation analysis heatmaps, significance analysis volcano plots, signaling pathway recognition bubble charts, and rectangular graphs were used for the analysis of differential metabolites and related signaling pathways. Results The red blood cell count, glucose, urea nitrogen, uric acid, and homocysteine levels in the MD group plateau pikas were higher than those in the MY group, while hemoglobin, hematocrit, creatinine, and carbon dioxide combining power were lower than those in the MY group. This indicated a significant difference in the blood oxygen-carrying capacity of plateau pikas at different altitudes. The principal component pattern recognition analyses, and OPLS-DA permutation test showed that the kidney metabolites of the MD and MY groups of plateau pikas had distinct clustering distributions (R²Y=0.930, Q²=0.655). According to the screening criteria and database comparison, 46 differential metabolites were identified in the kidneys of plateau pikas at different altitudes. In the MD group of plateau pikas, the expression levels of bufadienolide, adenosine, adenine, diosgenin, berberine chloride, carnosol, and astaxanthin were significantly increased (VIP>1.5, P<0.05), while the levels of arachidonic acid, histamine, and coumarin were significantly decreased (VIP>1.5, P<0.05). The analysis of related signaling pathways showed that the biosynthetic pathways of valine, leucine, and isoleucine had the largest impact factors (P<0.05), while the biosynthetic pathways of pantothenate and coenzyme A showed the most significant enrichment (P<0.05). Conclusion The differential metabolites of amino acids, pantothenate, and coenzyme A pathways in the kidneys of plateau pikas at different altitudes may be involved in the metabolic mechanisms of plateau pikas' hypoxia adaptation in high-altitude environments.

The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum (I. dunnianum) resulted in the isolation of five pairs of new lignans (1-5), and 7 known analogs (6-12). The separation of enantiomer mixtures 1-5 to 1a/1b-5a/5b was achieved using a chiral column with acetonitrile-water mixtures as eluents. The planar structures of 1-2 were previously undescribed, and the chiral separation and absolute configurations of 3-5 were reported for the first time. Their structures were determined through comprehensive spectroscopic data analysis [nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass (HR-ESI-MS), infrared (IR), and ultraviolet (UV)] and quantum chemistry calculations (ECD). The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide (LPS)-stimulated BV-2 cells. Compounds 1a, 3a, 3b, and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner. Western blot and real-time polymerase chain reaction (PCR) assays revealed that 1a down-regulated the messenger ribonucleic acid (mRNA) levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), COX-2, and iNOS and the protein expressions of COX-2 and iNOS. This research provides guidance and evidence for the further development and utilization of I. dunnianum.
Lignans/isolation & purification* ; Plant Leaves/chemistry* ; Anti-Inflammatory Agents/isolation & purification* ; Mice ; Animals ; Molecular Structure ; Plant Extracts/pharmacology* ; Illicium/chemistry* ; Cyclooxygenase 2/immunology* ; Interleukin-6/immunology* ; Nitric Oxide/metabolism* ; Cell Line ; Tumor Necrosis Factor-alpha/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Lipopolysaccharides

Objective To develop a novel transcatheter tricuspid valve replacement device and test its performance. Methods The transcatheter tricuspid valve stent consisted of double-layer self-expanding nitinol stent, biotissue-derived bovine pericardial leaflets, and PTFE woven. The delivery system, mainly consisting of a handle control unit and a delivery sheath, was sent to the correct position via right atrium or jugular vein. The sheath had a visualization feature, and the handle control unit could realize the functions of stable release and partial recovery of the interventional valve. In addition, this study performed animal survival experiments on the basis of in vitro experiments. A large-white pig was used as the experimental animal. Cardiopulmonary bypass was established through median thoracotomy, then the right atrium was opened, and the interventional valve was released under direct vision without cardiac arrest. Approximately 1 month after interventional valve implantation, the maneuverability and stability of the interventional tricuspid device were evaluated by autopsy. Results Through the animal experiment, the interventional valve was successfully released, and the anchoring was satisfactory. Postoperative transthoracic echocardiography showed that the interventional valve opened and closed well, the flow rate of tricuspid valve was 0.6 m/s, and there was no obvious tricuspid regurgitation. One month after the operation, we dissected the large-white pig and found the interventional valve was not deformed or displaced, the leaflets were well aligned, and there was thrombus attachment in the groove between the inner and outer layers of the interventional valve. Conclusion Animal experiment shows that the novel device can stably and firmly attach to the tricuspid annulus, with good anchoring effect, and effectively reduce paravalvular leakage.

Objective    To summarize the early outcomes of totally thoracoscopic minimally invasive aortic valve replacement (AVR) and double valve replacement (DVR). Methods    The clinical data of patients who underwent totally thoracoscopic minimally invasive AVR or DVR in Guangdong Provincial People’s Hospital from April 2020 to January 2021 were retrospectively analyzed. The patients were divided into an AVR group and a DVR group according to the surgical method, and the clinical data of the two groups were compared. Results    Finally 22 patients were enrolled, including 14 males and 8 females with an average age of 50.0±11.2 years at operation. Eight patients were degenerative disease, 8 were rheumatic heart disease combined with valvular disease, and 6 were bicuspid aortic valve. Out of the 22 patients, 16 underwent AVR alone, and 6 underwent DVR. All patients completed the operation successfully, and there was no death. Perivalvular leakage during surgery occurred in 2 patients. The average cardiopulmonary bypass time was 187.0±39.9 minutes, and aortic cross-clamping time was 117.0 (99.0, 158.0) minutes. Duration of mechanical ventilation and intensive care unit stay was 9.5 (4.8, 18.3) hours and 41.0 (34.0, 64.0) hours, respectively. The volume of chest drainage at the first 24 hours after surgery was 214.0±124.6 mL, and the postoperative hospital stay was 5.5 (4.0, 8.3) days. The cardiopulmonary bypass time and aortic cross-clamping time in the DVR group were longer than those in the AVR group, and the volume of chest drainage at 24 hours after surgery was more than that in the AVR group, with a statistical difference (P<0.05). Echocardiography before hospital discharge showed paravalvular leakage in 1 patient. There was no death during follow-up of 5.9±3.0 months. Conclusion    The early outcome of totally thoracoscopic minimally invasive AVR and DVR is satisfactory, and the approach of surgery is worth exploring.

Objective    To investigate the predictive value of right atrial myocardial fibrosis in the prognosis of isolated tricuspid regurgitation surgery after left heart valve surgery. Methods    The patients who underwent tricuspid valvuloplasty by the same operator in Guangdong Provincial People's Hospital from April 2016 to August 2021 due to long-term isolated severe tricuspid regurgitation after left heart valve surgery were included in the study. According to the degree of right atrial myocardial fibrosis, the patients were divided into three groups: a mild group, a moderate group, and a severe group. The clinical data of these patients were compared and analyzed. Results    A total of 75 patients were enrolled, including 16 males and 59 females with an average age of 57.0±8.4 years. There were 30 patients in the mild group, 29 patients in the moderate group and 16 patients in the severe group. In terms of the preoperative data, there were statistical differences in cardiac function grade, right atrial diameter, tricuspid incompetence area among the three groups (P<0.05). In terms of the postoperative data, there were statistical differences among the three groups in the cardiopulmonary bypass time, mechanical ventilation time, ICU monitoring time, complication rate and mortality (P<0.05). Further pairwise comparison showed that, compared with the mild group, the severe group had longer mechanical ventilation time (P=0.024), longer ICU monitoring time (P=0.003) and higher incidence of postoperative complications (P=0.024), while the moderate group had no statistical difference in all aspects (P>0.05); compared with the moderate group, the severe group had longer ICU monitoring time (P=0.021) and higher incidence of complications (P=0.006). Conclusion    The early outcome of tricuspid valvuloplasty in patients with isolated tricuspid regurgitation after left heart valve surgery with severe right atrial myocardial fibrosis is worse than that in the patients with mild and moderate fibrosis, suggesting that the degree of myocardial fibrosis in the right atrium can be a predictor of the effect of tricuspid regurgitation surgery and a judgement indicator of the surgery timing.

Objective:To investigate the short-term clinical outcomes of posterior percutaneous pedicle screw fixation combined with percutaneous vertebroplasty (PVP) for treating Kümmell's disease with intravertebral instability.Methods:A retrospective case series study was made on 18 patients with Kümmell's disease with intravertebral instability treated at Lishui Hospital of Zhejiang University from January 2012 to February 2016. There were 4 males and 14 females, aged 65-86 years [(76.0±5.5)years]. Segment of injury was T 7 in 1 patient, T 10 in 2, T 11 in 3, T 12 in 4, L 1 in 6, and L 2 in 2. All patients underwent posterior percutaneous pedicle screw fixation combined with PVP. The operation time, intraoperative blood loss, amount of cement injected into the vertebra, and length of postoperative hospital stay were recorded. The visual analogue scale (VAS), Oswestry disability index (ODI), Cobb angle, and wedge angle of the operative segment were recorded and compared preoperatively, postoperatively, and at the latest follow-up. Meanwhile, the complications were recorded. Results:All patients were followed up for 12-28 months [(17.7±4.4)months]. The operation time was 110-175 minutes [(137.9±21.9)minutes] and the blood loss was 50-165 ml [(110.7±35.6)ml]. The amount of cement injected into the vertebra was 2.5-6.0 ml [(4.7±0.9)ml]. The length of hospital stay was 7-14 days [(9.4±2.3)days]. The VAS was (7.8±1.2) points preoperatively, (3.3±0.7) points at 1 week postoperatively and (2.4±0.7)points at the latest follow-up. The ODI was (67.3±7.3)% preoperatively, (30.5±7.5)% at 1 week postoperatively and (21.8±8.3)% at the latest follow-up. The Cobb angle was (26.2±9.5)° preoperatively, (12.6±7.2)° at 1 week postoperatively and (16.7±6.2)°at the latest follow-up. The wedge angle was (21.1±6.1)° preoperatively, (8.4±4.6)° at 1 week postoperatively, and (13.2±4.1)° at the latest follow-up. The above clinical and radiological parameters were significantly improved after operation ( P<0.05), and showed no significant differences at the latest follow-up when compared to that at 1 week postoperatively ( P>0.05). Five patients showed slight screw loosening, but there was no obvious dislocation of internal fixation. One case developed distal vertebral compression fracture at 6 months postoperatively and cured after a second PVP. Conclusion:For Kümmell's disease with intravertebral instability, posterior percutaneous pedicle screw fixation combined with PVP can effectively restore and maintain the spinal sequence, rapidly relieve the pain and improve clinical function. However, the long-term efficacy needs further study.

Previous studies have shown that spinosin was implicated in the modulation of sedation and hypnosis, while its effects on learning and memory deficits were rarely reported. The aim of this study is to investigate the effects of spinosin on the improvement of cognitive impairment in model mice with Alzheimer’s disease (AD) induced by Aβ1–42 and determine the underlying mechanism. Spontaneous locomotion assessment and Morris water maze test were performed to investigate the impact of spinosin on behavioral activities, and the pathological changes were assayed by biochemical analyses and histological assay. After 7 days of intracerebroventricular (ICV) administration of spinosin (100 µg/kg/day), the cognitive impairment of mice induced by Aβ1–42 was significantly attenuated. Moreover, spinosin treatment effectively decreased the level of malondialdehyde (MDA) and Aβ1–42 accumulation in hippocampus. Aβ1–42 induced alterations in the expression of brain derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2), as well as inflammatory response in brain were also reversed by spinosin treatment. These results indicated that the ameliorating effect of spinosin on cognitive impairment might be mediated through the regulation of oxidative stress, inflammatory process, apoptotic program and neurotrophic factor expression, suggesting that spinosin might be beneficial to treat learning and memory deficits in patients with AD via multi-targets.
Alzheimer Disease* ; Animals ; B-Lymphocytes ; Brain ; Brain-Derived Neurotrophic Factor ; Cognition Disorders ; Hippocampus ; Humans ; Hypnosis ; Learning* ; Locomotion ; Malondialdehyde ; Memory Disorders ; Memory* ; Mice* ; Neuroprotection ; Neuroprotective Agents* ; Oxidative Stress ; Water

Objective To analyze functioning and disability, unmet needs and the service for people with disabilities in Shenzhen, Guangdong, China. Methods Based on International Classification of Functioning, Disability and Health (ICF) and World Report on Disabil-ity, the theoretical framework had been constructed, and the unmet needs and service status for people with disabilities in Shenzhen in 2015 had been statistically analyzed. Results For the statistics of disability by categories, physical disability composed of 42.5%, speech disability composed of 1.5%;people with severe and extremely severe disabilities composed of 52.8%;Futian District composed of 19.7%, Yantian District composed of 2.2%;people aged 0 to 18 years composed of 17.4%, and people aged over 60 years (27.0%) were the larger group. For the unmet needs of people with disabilities, 25%needed rehabilitation therapy, 18.8%needed functional training, 23.2%needed assis-tive devices, and 32.9%had no need. For rehabilitation sevice in Shenzhen, 24.4%received rehabilitation therapy, 17.4%received function-al training, 20.4%received assistive devices, and 37.6%did not receive any service. For the barrier-free reconstruction, 4.6%needed bath-room reconstruction, and 0.7%needed internet access screen software. Conclusion The status of functioning and disability, unmet needs and service development of rehabilitation in Shenzhen had been analyzed. There was still a gap between unmet needs and services of rehabilita-tion. It recommended to construct precise services delivery based on unmet needs, improve the full coverage and quality of service of reha-bilitation.

Aim To investigate the effects of diterpene ginkgolides meglumine injection (DGMI ) on amino acids and monoamine neurotransmitters in rats with cerebral ischemia/reperfusion injury.Methods In-traluminal suture was applied to establish middle cere-bral artery occlusion (MCAO/R)model with ischemia for 1.5 h and reperfusion for 24 h.After the adminis-tration of DGMI (i.v.),the levels of amino acid and monoamine neurotransmitters in brain tissue were de-tected through HPLC-ECD.Results DGMI down-reg-ulated the concentrations of aspartic acid, glutamic acid,glycine and γ-aminobutyric acid which were in-creased in MCAO/R group.DGMI also reduced the levels of norepinephrine epinephrine,glyoxylic acid, serotonin and 5-HIAA in cortex and hippocampus,and increased adrenaline content compared to the model group.Conclusion DGMI exhibits a protective role in rats with cerebral ischemia /reperfusion injury through regulating amino acids and monoamine neuro-transmitters.

The normative research on safeguarding intangible cultural heritage of traditional Chinese medicine is the important measure after building list and filing work of Convention of the protection of intangible cultural heritage of UNESCO, and also a strategy in accordance with the principle of the protection of traditional knowledge of traditional Chinese medicine.This article discussed the arrangement and standardization in the academic level of folk medicine technology teaching orally from generation to generation, to provide protection for the living inheritance of intangible cultural heritage of traditional Chinese medicine, and a pilot measure for the construction of intangible cultural heritage protection system.