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Objective:To verify the clinical efficacy and safety of Qufeng Tongxuan method in treating low- and moderate-volume intracerebral hemorrhage at acute stage.Methods:A prospective, multicenter, randomized, double-blind, placebo-controlled study was performed; patients with low- and moderate-volume intracerebral hemorrhage at the basal ganglia and/or thalamus accepted treatment in 16 hospitals from September 2019 to April 2022 were enrolled. These patients were divided into experimental and control groups with a block randomized method by SAS software. Patients in control group were given conventional western medicine treatment; those in experimental group accepted Qufeng Tongxuan method (sequential therapy of Shexiang Huayu Xingnao granules and Zhilong Huoxue Tongyu granules) besides conventional western medicine treatment. NIHSS was used to assess neurological function before treatment and on 7 th, 14 th, 30 th, and 90 th d of treatment. Prognoses of these patients were assessed by modified Rankin scale (mRS) before treatment and on 180 th d of treatment. Brain CT was performed before treatment and on 7 th and 14 th d of treatment to calculate the hematoma volume. Before treatment and on 14 th d of treatment, changes of coagulation function, liver and kidney functions of the 2 groups were compared. Adverse reactions during treatment in the 2 groups were recorded. Results:No significant differences in NIHSS scores were noted between the 2 groups before treatment, on 7 th, 14 th, and 30 th d of treatment ( P>0.05); NIHSS scores in experimental group on 90 th d of treatment were signficantly lower than those in control group ( P<0.05); NIHSS scores in experimental group decreased gradually before treatment and on 7 th, 14 th, 30 th and 90 th d of treatment, with statistical significances ( P<0.05). No significant differences in mRS scores were noted between the 2 groups before treatment ( P>0.05); mRS scores in experimental group on 180 th d of treatment were signfciantly lower than those in control group ( P<0.05). No significant difference in hematoma volume was noted between the 2 groups before treatment and on 7 th and 14 th d of treatment ( P>0.05); both groups had gradually decreased hematoma volumes before treatment and on 7 th and 14 th d of treatment, respectively, with significant differences ( P<0.05); the volume difference of hematoma between 14 th d of treatment and before treatment in experimental group (6.42[4.10, 11.73]) was significantly higher than that in control group (4.00[1.25, 10.58], P<0.05). No significant differences in liver and kidney function indexes or coagulation function indexes were noted between the 2 groups before treatment and on 14 th d of treatment ( P>0.05). Adverse reaction incidence was 9.52% ( n=12) in experimental group and 10.34% ( n=12) in control group, without statistical difference ( P>0.05). Conclusion:Under premise of conventional western medicine treatment, Qufeng Tongxuan method can promote hematoma absorption and improve neurological deficit symptoms in low- and moderate-volume intracerebral hemorrhage at acute stage, without obvious adverse reactions.
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Objective:To investigate the amyloid precursor protein (APP) expression in brain glioma tissues and cerebrospinal fluid of glioma patients and their significances.Methods:(1) Fifty-six brain glioma specimens surgically resected and pathologically confirmed in our hospital from January 2015 to December 2020 were collected, including 9 with WHO grading I, 14 with WHO grading II, 18 with WHO grading III, and 15 with WHO grading IV. In addition, the necrotic brain tissues of 4 patients with hypertensive intracerebral hemorrhage during hematoma removal at the same time period were collected as controls. Western blotting and real-time quantitative PCR (RT-qPCR) were used to detect the APP protein and mRNA expressions in glioma tissues and control brain tissues, respectively. (2) The cerebrospinal fluid of above 56 patients with glioma, 4 patients with viral meningitis, 4 patients with bacterial meningitis, 4 patients with autoimmune encephalitis, 5 patients with epilepsy, 3 patients with migraine and 3 normal subjects were collected at the same time period, and the APP content in the cerebrospinal fluid of all subjects were detected by ELISA.Results:(1) Western blotting and RT-qPCR showed that the APP protein and mRNA expressions in glioma tissues of WHO grading I, II, III and IV were significantly higher than those in control brain tissues, and the APP protein and mRNA expressions in glioma tissues of WHO grading I, II, III and IV increased successively, with statistical differences ( P<0.05). There were no significant differences in APP protein and mRNA expressions between first-onset glioma and recurrent glioma in glioma tissues of WHO grading I and II ( P>0.05); while in glioma tissues of WHO grading III and IV, APP mRNA expression in recurrent glioma was statistically higher than that in first-onset glioma ( P<0.05). (2) ELISA results showed that APP content in patients with viral meningitis, bacterial meningitis, autoimmune encephalitis, epilepsy or migraine was not significantly different as compared with that in normal controls ( P>0.05). The APP content in cerebrospinal fluid of patients with WHO grading I, II, III and IV gliomas was significantly higher than that in normal controls, and the APP content in cerebrospinal fluid of patients with WHO grading I, II, III and IV gliomas increased successively, with statistical differences ( P<0.05). Conclusion:APP is highly expressed in glioma tissues and cerebrospinal fluid of patients with glioma, and its expression is significantly correlated with the pathological grades of glioma; the detection of APP expression in cerebrospinal fluid can be used as a new screening method for glioma patients.
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The treatment of large-segment bone defects is a severe trouble. The emergence of bone tissue engineering, a current research hotspot, has brought promising treatment strategies to this field. Bone marrow mesenchymal stem cells (BMSCs), as a kind of seeding cells for bone tissue engineering, have multipotentials, including easy isolation and culture, abundant sources and easy to expand. BMSCs can be differentiated into osteoblasts by a variety of methods to achieve the purpose of bone repairing. Currently, the components to induce osteogenic differentiation of BMSCs include cellular factors, hormones, biological materials, traditional Chinese medicine, physical stimulation and non-coding RNA. Osteogenic differentiation of BMSCs is a very complex process, which is controled by kinds of signaling pathways to maintain a balanced in bone metabolism, mainly including BMPs/Smad signaling pathway, transforming growth factor-β signaling pathway, Wnt signaling pathway, etc. The development of active factors and scaffold which can induce osteogenic differentiation of BMSCs is the basis for the development of bone tissue engineering. Further exploration of signaling pathways could reveal some specific molecular mechanisms and find new therapeutic targets in regeneration medicine. However, some issues, such as osteoblasts differentiation of BMSCs, mutual interference of signal pathways, clinical transformation and clinical application, are still needed to be resolved.
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Objective:To investigate the effects of tantalum coating on adhesion, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. Methods:In this study, BMSCs were extracted from 6 6-week-old rats and cultured in vitro to the third generation. Tantalum coating was manufactured on Ti6Al4V by chemical vapor deposition. The cells were identified by flow cytometry before they were induced with different mediums for osteogenesis, chondrogenesis and adipogenesis. The adhesion, proliferation and osteogenic differentiation of BMSCs were detected with fluorescence staining, Cell Counting Kit-8 (CCK8) assay and Q-PCR, respectively. Recorded and compared were the adhesion rate, proliferation rate, and expression of osterix (OSX), Runt-related transcription factor 2 (RUNX2), osteonectin (OSN) and osteopontin (OPN) of BMSCs on the surface of titanium alloy round plates (the Ti6Al4V group) and of tantalum coating round plates (the Ta group). Results:The flow cytometry revealed CD44 (94.55%), CD90 (95.01%) and CD34 (0.06%). Alkaline phosphatase (ALP) staining was positive after osteogenic induction for 14 days; Alizarin red staining showed calcified nodules after osteogenic induction for 21 days; oil red O staining was positive after adipogenic induction for 21 days; alcian blue staining found chondrogenic ability after chondrogenic induction for 21 days. Laser confocal microscopy showed that the BMSCs grew in patches aggregated and closely linked on the surface of titanium alloy round plates (in the Ti6Al4V group) and of tantalum coating round plates (in the Ta group). More BMSCs adhered on the tantalum coating plates than on the titanium alloy plates and exhibited better ductility. The proliferation rates of BMSCs on tantalum coating were significantly faster than those on titanium alloy after 1, 3, 5 and 7 days of co-culture in vitro ( P<0.05).Q-PCR showed that tantalum coating promoted the expression of OSN and OPN after 7 days of culture significantly higher than titanium alloy did ( P<0.05).After 21 days of co-culture in vitro, tantalum coating enhanced the expression of OSX, RUNX2, OSN and OPN significantly higher than titanium alloy did ( P<0.05). Conclusion:Compared to titanium alloy which is used for conventional orthopedic implants, tantalum coating can observably promote adhesion, proliferation and osteogenic differentiation of BMSCs.
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Objective To explore the mechanism of apoptosis after cryotherapy on tumors.Methods (1) GL261 glioma cells (1×107 cell/10 μL) were injected into the subcutaneous one ofC57 mice to establish tumor-bearing mouse models;when the diameter of tumor reached to 15-20 mm,the mice were randomly divided into cryogenic treatment group and sham-operated group (n=1 0);mice in the cryogenic treatment group were given surgical cryotherapy,while those in the sham-operated group only performed surgery without cryotherapy.TUNEL was used to detect the cell apoptosis in glioma tissues 12 and 24 h after operation;and Western blotting was employed to detect the protein expressions of pro-caspase-8,pro-caspase-9 and poly-ADP-ribose polymerase (PARP).(2) GL261 glioma cells were divided into control group and one time cryogenic release group,and DMEM and one time of cryogenic release were given to the two groups,respectively;12 h after the treatment,TUNEL was used to observe the cell apoptosis in glioma tissues,and Western blotting was employed to detect the protein expressions.Results (1) TUNEL indicated that the cells in the S1 region of the glioma tissues from mice in the cryogenic treatment group were uniformly died;significant apoptosis was noted in cells of the S2 region at 12 h after treatment;while,24 h after treatment,S1 region still showed uniform necrosis,S2 region showed apoptotic regression,and S3 region showed new apoptosis at the target side.Western blotting indicated that pro-caspase-9 and PARP protein expressions at the S2 region were signficantly decreased as compared with those at the S1,S3 and S4 regions (P＜0.05),and pro-caspase-8 protein expression at the S3 region were signficantly reduced as compared with those at the S1,S2 and S4 regions in the cryogenic treatment group (P＜0.05).(2) TUNEL showed that significantly increased GL261 glioma cell apoptosis rate was noted in the one time cryogenic release group as compared with that in the control group (P＜0.05);Western blotting indicated that as compared with the control group,the cryogenic release group had significantly decreased pro-caspase-8 and pro-caspase-9 expressions (P＜0.05).Conclusion Cryogenic release or substances released from tumor tissues after cryoablation shows an effect on promoting apoptosis.