Objective To observe the effects of total saponins of Trillium tschonoskii Maxim(TST)on vascular cognitive impairment(VCI),neurovascular units(NVUs),and neural circuit integrity in rats.Methods Forty-eight male Sprague-Dawley(SD)rats were randomly divided into sham-operated group,model group,TST group(intragastric administration,100 mg/kg),and donepezil group(intragastric administration,0.45 mg/kg),and then subjected to ischemic stroke by 2-VO method(bilateral common carotid artery ligation)or sham surgery.After 28 days of intragastric administration,Mirros water maze test was performed to evaluate the spatial learning and memory abilities of rats in each group.HE and Nissl staining were used to observe the pathological changes of brain tissue in rats.The expression of synuclein(SYN)in rat hippocampus was observed by immunohistochemical staining.Changes in dendritic spines in rat's hippocampal neurons were observed by Golgi staining.Western blotting was used to detect the expression levels of IL-1β,IL-10,vascular endothelial growth factor A(VEGFA),postsynaptic density protein 95(PSD95),and growth associated protein 43(GAP43)in rat's hippocampus in each group.Results In Mirros water maze test,rats in model group showed significant prolonged escape latency(P＜0.05),and a significant reduction in the number of crossing platforms and the percentage of activity time in the target quadrant(P＜0.05)than those in sham-operated group;while rats in TST group and donepezil group showed significant shortened escape latency(P＜0.01),and significant increase of the number of times of crossing platforms and the percentage of activity time in the target quadrant(P＜0.05)than those in model group.Compared of sham-operated group,model group showed a decrease in the expression of SYN and the number of neurons,Nissl bodies,and dendritic spines in the CA1 region of the hippocampus(P＜0.05).Compared with model group,TST group and donepezil group showed an increase in the expression of SYN and the number of neurons,Nissl bodies,and dendritic spines in the CA1 region of the hippocampus(P＜0.05).Western blotting showed a significant increase in the expression of IL-1β and VEGF(P＜0.05),and a decrease in the expression of IL-10,PSD95,and GAP43(P＜0.01)in rat's hippocampus of model group than those in sham-operated group.Compared with model group,TST group and donepezil group showed a significant decrease in the expression of IL-1β(P＜0.05),and an increase in the expression of VEGFA,IL-10,and GAP43(P＜0.05).Conclusions TST could alleviate cognitive impairment through promoting synaptic plasticity and neurovascular unit remodeling in 2-VO model rats,suggesting its significance as a potential drug for apoplexy.

Objective:To explore and stimulate the pathway mechanism for doctors from core hospitals,which are the high-quality medical resources in loose medical alliances,to sink to the grassroots level on their own initiative and continue to participate in the co-operation,so as to provide useful references for improving the effectiveness of cooperation within medical alliances.Methods:The fuzzy set Qualitative Comparative Analysis(fsQCA)method was used to investigate 205 doctors in the core hospitals of a loose medical alliance in District X of City B.This investigation was grounded in relationship commitment theory,motivation theory,social exchange theory,and cooperation reinforcement theory.Results:The level of relationship commitment of doctors in the core hospitals to proactively participate in cooperation was influenced by multiple factors,including doctors'perception of job significance,opportunity cost perception,organizational support,and teamwork experience.This resulted in the formation of three concurrent driving mechanism pathways:merger-driven effect,experience-enhancing effect,and altruistic trigger effect.Among these factors,the perception of work significance was a necessary condition,and cooperative experience played an important role in doctors'continuous participation.Conclusion:The level of relational commitment of doctors to participate in cooperative efforts is driven by a combination of various factors,with different incentive mechanisms exhibiting heterogeneity within loose medical alliances.Designing appropriate incentive and support strategies tailored to specific contexts can effectively drive the proactive downward flow of high-quality medical resources from core hospitals within loose medical alliances.

OBJECTIVES: To study the effect of ligustrazine injection on mitophagy in neonatal rats with hypoxic-ischemic encephalopathy (HIE) and its molecular mechanism. METHODS: Neonatal Sprague-Dawley rats, aged 7 days, were randomly divided into a sham-operation group with 8 rats, a model group with 12 rats, and a ligustrazine group with 12 rats. The rats in the model group and the ligustrazine group were used to establish a neonatal rat model of HIE by ligation of the left common carotid artery followed by hypoxia treatment, and blood vessels were exposed without any other treatment for the rats in the sham-operation group. The rats in the ligustrazine group were intraperitoneally injected with ligustrazine (20 mg/kg) daily after hypoxia-ischemia, and those in the sham-operation group and the model group were intraperitoneally injected with an equal volume of normal saline daily. Samples were collected after 7 days of treatment. Hematoxylin and eosin staining and Nissl staining were used to observe the pathological changes of neurons in brain tissue; immunohistochemical staining was used to observe the positive expression of PINK1 and Parkin in the hippocampus and cortex; TUNEL staining was used to measure neuronal apoptosis; Western blotting was used to measure the expression levels of the mitophagy pathway proteins PINK1 and Parkin and the autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and ubiquitin-binding protein (P62). RESULTS: Compared with the sham-operation group, the model group had a significant reduction in the number of neurons, an increase in intercellular space, loose arrangement, lipid vacuolization, and a reduction in Nissl bodies. The increased positive expression of PINK1 and Parkin, apoptosis rate of neurons, and protein expression levels of PINK1, Parkin, Beclin1 and LC3 (P<0.05) and the decreased protein expression level of P62 in the hippocampus were also observed in the model group (P<0.05). Compared with the model group, the ligustrazine group had a significant increase in the number of neurons with ordered arrangement and an increase in Nissl bodies, significant reductions in the positive expression of PINK1 and Parkin, the apoptosis rate of neurons, and the protein expression levels of PINK1, Parkin, Beclin1, and LC3 (P<0.05), and a significant increase in the protein expression level of P62 (P<0.05). CONCLUSIONS Ligustrazine can alleviate hypoxic-ischemic brain damage and inhibit neuronal apoptosis in neonatal rats to a certain extent, possibly by inhibiting PINK1/Parkin-mediated autophagy.
Rats ; Animals ; Hypoxia-Ischemia, Brain/metabolism* ; Animals, Newborn ; Rats, Sprague-Dawley ; Beclin-1 ; Autophagy ; Ubiquitin-Protein Ligases/metabolism* ; Protein Kinases/metabolism*

OBJECTIVE: To investigate the clinical application of two elastic pedicle internal fixation systems in single-segment lumbar disc herniation fenestration. METHODS: A retrospective analysis of 64 patients with lumbar intervertebral disc herniation treated by surgery from June 2019 to March 2021. According to the different elastic fixation systems placed during the operation, the patients were divided into ordinary pedicle screw elastic rod link group (elastic rod group) and a special elastic pedicle screw rigid rod fixed connection group (elastic screw group). There were 33 cases in the elastic rod group, including 18 males and 15 females, aged from 30 to 69 years old with an average of(49.18±10.23) years old;and 31 cases in the elastic screw group, including 16 males and 15 females, aged from 32 to 68 with an average of (49.81±9.24) years old. The operation time, intraoperative blood loss, postoperative wound drainage, and postoperative landing time of the two groups were recorded separately. The visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) score, and Oswestry Disability Index (ODI) were compared before and 3, 12 months after operation. The height of the adjacent vertebral space on the lateral DR film before and 12 months after the operation was measured. The clinical efficacy was evaluated by Macnab standard. RESULTS: All the patients successfully completed the operation, and were followed up. The operation time, intraoperative blood loss, postoperative wound drainage and postoperative landing time in the elastic rod group were(63.73±12.01) min, (89.55±16.07) ml, (81.67±16.00) ml, (3.45±0.75) d , while in the elastic nail group was (62.96±11.54) min, (88.35±17.14) ml, (82.29±15.40) ml, (3.29±0.78) d, the difference was not statistically significant. The symptoms of low back pain and lower extremity numbness were significantly improved in all patients after operation. There was no significant difference in VAS, JOA score and ODI between the two groups before and after surgery (P>0.05). At 12 months after operation, there was no significant difference in the height of the adjacent vertebral space between the upper adjacent vertebral body and the same segment before operation(P>0.05), and there was no significant difference between the groups before and after the operation. According to Macnab criteria, the elastic rod group was excellent in 30 cases, good in 2 cases, fair in 1 case, while the elastic nail group was excellent in 29 cases, good in 2 cases, fair in 0 cases, and there was no significant difference(Z=-0.42, P=0.68). CONCLUSION In fenestrated nucleus pulposus extraction for lumbar disc herniation, the two elastic pedicle internal fixation systems are equally effective and can be used. The elastic screw internal fixation system has certain advantages when the distance between the two vertebral bodies is short, and the elastic rod cannot be placed or is difficult to be placed, and it is more widely used.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Intervertebral Disc Displacement/surgery* ; Lumbar Vertebrae/surgery* ; Spinal Fusion ; Nucleus Pulposus ; Retrospective Studies ; Pedicle Screws ; Treatment Outcome ; Postoperative Hemorrhage

Objective: To investigate the clinicopathological characteristics of H3K27-altered diffuse midline glioma (DMG), and to analyze DMG's prognostic factors, and subsequently, to study the possibility of using NTRK as a therapeutic target for DMG. Methods: A total of 232 DMG diagnosed at the Sanbo Brain Hospital, Capital Medical University, Beijing, China from July 2016 to March 2021 were collected. Their clinical, radiological and pathological features, the ratio of MGMT promoter methylation, expression of NTRK, and characteristics of NTRK gene fusion were analyzed. The prognostic values of different factors were also studied, including age, tumor location, histological grade, gene and protein expression of NTRK, and postoperative adjuvant therapy. Results: Among the 232 DMG cases, there were 8 patients with both primary and relapse tumors on the record. Thus, a total of 224 patients were analyzed, including 118 males and 106 females. There were 126 adults (>18 years of age) and 98 children (≤18 years of age). Notably, the most frequent location was thalamus (41/126, 32.5%) in adults, but brainstem (59/96, 60.2%) in children. The lesions showed T1 hypointensity or isointensity, and T2 hyperintensity. However, contrast enhancement patterns of the tumors varied, with many tumors lacking contrast-enhancing. The histological grades included grade 2 (9/224, 4.0%), grade 3 (41/224, 18.3%) and grade 4 (174/224, 77.7%). Two hundred and twenty-four DMGs were diffusely positive for H3K27M and negative for H3K27me3. The ratio of MGMT promoter methylation was low (1/45, 2.2%). One hundred and seventy-seven of the 224 cases (177/224, 79.0%) were positive for NTRK. Fifty cases were analyzed using fluorescence in situ hybridization. Among them, five DMGs (positive rate, 10.0%) were NTRK fusion positive. This study showed that there were no differences between adult and pediatric DMGs in histological grading, expression of NTRK, and NTRK gene fusion. One hundred and fifty-nine patients were included in the follow-up analysis (P>0.05). During the follow-up period, 109/159 patients (69.6%) died of the disease, with a median survival time of 12 months (range 1 to 55 months). Univariate log-rank analysis showed that age, location, surgical procedure and postoperative adjuvant therapy were associated with overall survivals of the DMG patients (P<0.05). Conclusions: The prognosis of DMG is poor overall. There are differences between adult and pediatric DMGs in anatomic location and prognosis, but not in other features. NTRK1 gene fusion is detected in 10.0% of the tumors. It suggests that TRK inhibitor might be a choice for treating DMG.
Adult ; Male ; Female ; Humans ; Child ; Aged, 80 and over ; In Situ Hybridization, Fluorescence ; Glioma/pathology* ; Prognosis ; Gene Fusion ; Promoter Regions, Genetic

Objective: To investigate the clinicopathological characteristics and differential diagnosis of pediatric SMARCB1/INI1-deficient poorly differentiated chordoma (PDC) of the skull base. Methods: Five cases of SMARCB1/INI1-deficient PDC were identified in 139 cases of chordoma diagnosed in Sanbo Brain Institute, Capital Medical University, Beijing, China from March 2017 to March 2021. The clinical and imaging data of the 5 PDCs were collected. H&E and immunohistochemical staining, and DNA methylation array were used, and the relevant literatures were reviewed. Results: All 5 PDCs were located at the clivus. The average age of the patients was 6.4 years, ranging from 3 to 16 years. Three patients were female and two were male. Morphologically, in contrast with classical chordomas, they presented as epithelioid or spindle tumor cells organized in sheets or nests, with necrosis, active mitoses, and infiltration into surrounding tissue. All cases showed positivity of CKpan, EMA, vimentin and brachyury (nuclear stain), and loss of nuclear SMARCB1/INI1 expression. S-100 protein expression was not frequent (2/5). Ki-67 proliferative index was high (20%-50%). All cases had over-expressed p53. It was necessary to differentiate SMARCB1/INI1-dificient PDC from SMARCB1/INI1-dificient tumors occurring at skull base of children or the tumors with epithelial and spindle cell morphological features. The 3 PDCs with DNA methylation testing showed the methylation profiles different from the pediatric atypical teratoid/rhabdoid tumors. They formed an independent methylation profile cluster. The clinical prognosis of the 5 patients was poor, and the overall survival time was 2-17 months. Conclusions: PDC is a special subtype of chordoma, which often affects children and occurs in the clivus. The PDC shares epithelioid or spindle cell morphologic features which are different from the classic chordoma. Besides the typical immunohistochemical profile of chordoma, PDC also has loss of nuclear SMARCB1/INI1 expression and distinct epigenetic characteristics.
Biomarkers, Tumor/genetics* ; Child ; Chordoma/genetics* ; Diagnosis, Differential ; Female ; Humans ; Male ; Prognosis ; Rhabdoid Tumor/diagnosis* ; SMARCB1 Protein/genetics* ; Skull Base

In this study, the antioxidant property changes in fermented Ziziphi Spinosae Semen(FZSS) with Poria cocos were analyzed by DPPH, ABTS and FRAP methods. Then the content determination of active ingredients and ~1H nuclear magnetic resonance(~1H-NMR) spectroscopy were also used to investigate the mechanism of FZSS with P. cocos in enhancing the antioxidant activity. The results showed that the content of active ingredients such as total phenols, total saponins and total polysaccharides were significantly increased during the fermentation time. The results of ~1H-NMR metabonomics showed that the contents of amino acids such as leucine, lysine, valine and alanine, nitrogen compounds such as creatine, creatinine, and betaine, and secondary metabolites, for instance, jujuboside A and spinosin were higher after fermentation, and above components showed positive correlation with antioxidant capacity in Pearson correlation analysis. Therefore, it was inferred that the enhancement of antioxidant activity of FZSS may be the result of the joint action of various chemical components. This study preliminarily clarified the mechanism of FZSS in enhancing the antioxidant activity, and provided new research ideas for the product development and utilization of FZSS.
Antioxidants ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Poria ; Semen ; Wolfiporia ; Ziziphus

According to the research strategy of resource chemistry of Chinese medicinal materials and Chinese medicinal resources recycling utilization, this study intends to explore the potential resource-oriented utilization value of the seed of Sophora flavescens by contrasting with its kindred plant S. alopecuroides. This study established a rapid UPLC-Q-TOF-MS/MS and UPLC-TQ-MS/MS method to determine the alkaloids in the seed of S. flavescens. Results of UPLC-Q-TOF-MS/MS analysis showed that the alkaloids in the seed of S. flavescens were highly similar with S. alopecuroides.In the determination of 7 kinds of alkaloids, the total content was 11.203 and 15.506 mg•g⁻¹ in the seed of S. flavescens and S. alopecuroides, respectively. The content of oxymatrine, oxysophocarpine and sophoridine is high in the seed of S. flavescens. The results indicated that the seeds of S. flavescens. could be an important material resource to obtain alkaloids.

Animals ; Cellular Reprogramming ; Dentate Gyrus ; cytology ; Fibroblasts ; cytology ; Mice ; Neural Stem Cells ; cytology ; transplantation ; Swine

OBJECTIVETo investigate the clinicopathologic features, pathogenesis, diagnostic criteria and the relationship between different classification models and prognosis in Chinese patients with DLBCL, and try to look for the most appropriate classification model to predict clinical prognosis and therapeutic responses for Chinese patients with DLBCL.

METHODS181 cases of Chinese DLBCLs diagnosed according to the WHO 2008 classification were collected. Standard two-step Envision method of immunohistochemical staining was used to assess the expressions of CD20, CD3ε, CD79a, CD10, Mum-1, Bcl-6, GCET-1, FOXP1 and Ki-67. The phenotypic classifications were assessed according to the standard of Hans model and Chan model. Data were analyzed by χ(2) test and Life Table survival analysis with the SPSS14.0 statistical package.

RESULTSThe ratio of male to female in this cohort was 1.26:1. The median age of all patients was 57 yrs with the average age of 53.5 yrs. Of 61 cases (33.7%) primarily showed lymph node involvement. Gastrointestinal tract as the most involved extra-nodal organ was observed in 43 cases (35.8%). All patients with complete clinical follow-up materials survived from 1 - 120 months. The patients showed a high risk for death in the initial one and half years. Three year survival rate was 49.7% (90/181). Three year survival of 44 cases received R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, bolus) was 76.9% (20/26), whereas 61.9% (60/97) in 119 cases received CHOP alone, R-CHOP group showed better prognosis (P = 0.017). All cases expressed one or more pan B cell markers, such as CD20 (176/179, 98.3%) and CD79a (62/77, 80.5%). For Hans model, 78 cases were classified as GCB group, while 103 cases as Non-GCB group. The ratio of Non-GCB to GCB was 1.32 without difference on the survival (P > 0.05). For the Chan's algorithm, 68 cases belonged to GCB subgroup, while 113 cases non-GCB subgroup. The ratio of non-GCB to GCB was 1.66. GCB subtype showed much better prognosis than non-GCB subtype according to Life Table survival analysis (P < 0.05).

CONCLUSIONThe epidemiology and clinicopathologic features of Chinese DLBCLs were similarly with the western cases. Chan's algorithm was a significant tool to predict the cell origin and clinical biology of Chinese DLBCLs.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Algorithms ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; classification ; diagnosis ; pathology ; Male ; Middle Aged ; Models, Theoretical ; Prognosis ; Young Adult