The inflammatory cytokine interleukin-1 beta （IL-1β） plays a key role in the process of intervertebral disc degenera- tion （IVDD）. In the present study, we aimed to evaluate the effect of pharmaco-serum of ＂Taor...The inflammatory cytokine interleukin-1 beta （IL-1β） plays a key role in the process of intervertebral disc degenera- tion （IVDD）. In the present study, we aimed to evaluate the effect of pharmaco-serum of ＂Taoren-Honghua-herb pair＂ on IL-1β- induced chondrocyte degeneration in vitro. Taoren （Semen persicae） and Honghua （Safflower carthamus） were administered to the rats, and the pharmaco-serum was collected and prepared. Chondrocytes of the third passage, isolated from the rat＇s vertebral endplates, were treated by standard medium only （Group NC）, IL-1β （Group IL） or combination of IL-1β and pharmaco-serum （Group TRHH）. Cell proliferation and apoptosis were determined, and the expression of aggrecan, Col2ul, Coll0ul, IL-6 and SOX9 at the mRNA level in chondrocytes was quantified by real-time PCR. Immunohistochemistry staining of type II and X collagen and Safranine O staining were also used to evaluate the chondrocytes. Compared with the Group NC, IL-1β treatment inhibited the cell proliferation and induced the cell apoptosis （P〈0.05）, and the expression of aggrecan, Col2αl and SOX9 at the mRNA level was down-regulated. In contrast, the expression of Coll0ul and IL-6 was up-regulated after IL-1β treatment （P〈0.05）. Meanwhile, the immune-staining of type II collagen and Safranine O staining were decreased, while the staining of type X collagen was increased. Compared with the Group IL, cell proliferation was increased, and apoptosis of chondrocytes was decreased when cells were treated with the pharmaco-semm of TRHH-herb pair （P〈0.05）. The expression of aggrecan, Col2cd and SOX9 at the mRNA level was up-regulated, while that of Coll0cd and IL-6 was down-regulated （P〈0.05）. Saffanine O staining also showed increased positive staining （P〈0.05）. Taken together, the treatment of pharmaco-serum of TRHH-herb pair could prevent endplate chondrocyte degeneration induced by IL-1β.展开更多
Intervertebral disc （IVD） degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about ...Intervertebral disc （IVD） degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about how mechanical stress regulates nucleus notochordal （NC） cells to maintain IVD homeostasis. Here we report that mechanical stress can result in excessive integrin αvβ6-mediated activation of transforming growth factor beta （TGFβ）, decreased NC cell vacuoles, and increased matrix proteoglycan production, and results in degenerative disc disease （DDD）. Knockout of TGFβ type II receptor （TβRII） or integrin αv in the NC cells inhibited functional activity of postnatal NC cells and also resulted in DDD under mechanical loading. Administration of RGD peptide, TGFβ, and αvβ6-neutralizing antibodies attenuated IVD degeneration. Thus, integrin-mediated activation of TGFβ plays a critical role in mechanical signaling transduction to regulate IVD cell function and homeostasis. Manipulation of this signaling pathway may be a potential therapeutic target to modify DDD.展开更多
Objective:Studies have shown that docosahexaenoic acid(DHA)has a beneficial effect in the treatment of spinal cord injury.A meta-analysis was used to study the effect of DHA on the neurological recovery in the rat spi...Objective:Studies have shown that docosahexaenoic acid(DHA)has a beneficial effect in the treatment of spinal cord injury.A meta-analysis was used to study the effect of DHA on the neurological recovery in the rat spinal cord injury model,and the relationship between the recovery of motor function after spinal cord injury and the time and method of administration and the dose of DHA.Data source:Published studies on the effect of DHA on spinal cord injury animal models from seven databases were searched from their inception to January 2019,including PubMed,MEDLINE,EMBASE,the China National Knowledge Infrastructure,Wanfang,VIP,and SinoMed databases.The search terms included“spinal cord injury”“docosahexaenoic acid”,and“rats”.Data selection:Studies that evaluated the influence of DHA in rat models of spinal cord injury for locomotor functional recovery were included.The intervention group included any form of DHA treatment and the control group included treatment with normal saline,vehicle solution or no treatment.The Systematic Review Centre for Laboratory animal Experimentation’s risk of bias assessment tool was used for the quality assessment of the included studies.Literature inclusion,quality evaluation and data extraction were performed by two researchers.Meta-analysis was then conducted on all studies that met the inclusion criteria.Statistical analysis was performed on the data using RevMan 5.1.2.software.Outcome measures:The primary outcome measure was the score on the Basso,Beattie,and Bresnahan scale.Secondary outcome measures were the sloping plate test,balance beam test,stair test and grid exploration test.Results:A total of 12 related studies were included,3 of which were of higher quality and the remaining 9 were of lower quality.The highest mean Basso,Beattie,and Bresnahan scale score occurred at 42 days after DHA treatment in spinal cord injury rats.At 21 days after treatment,the mean difference in Basso,Beattie,Bresnahan scores between the DHA group and the control group was the most significant(pooled MD=4.14;95%CI=3.58–4.70;P<0.00001).In the subgroup analysis,improvement in the Basso,Beattie,and Bresnahan scale score was more significant in rats administered DHA intravenously(pooled MD=2.74;95%CI=1.41–4.07;P<0.0001)and subcutaneously(pooled MD=2.99;95%CI=2.29–3.69;P<0.00001)than in the groups administered DHA orally(pooled MD=3.04;95%CI=–1.01 to 7.09;P=0.14).Intravenous injection of DHA at 250 nmol/kg(pooled MD=2.94;95%CI=2.47–3.41;P<0.00001]and 1000 nmol/kg[pooled MD=3.60;95%CI=2.66–4.54;P<0.00001)significantly improved the Basso,Beattie,and Bresnahan scale score in rats and promoted the recovery of motor function.Conclusion:DHA can promote motor functional recovery after spinal cord injury in rats.The administration of DHA by intravenous or subcutaneous injection is more effective than oral administration of DHA.Intravenous injection of DHA at doses of 250 nmol/kg or 1000 nmol/kg is beneficial.Because of the small number and the low quality of the included studies,more high-quality research is needed in future to substantiate the results.展开更多
OBJECTIVE： To investigate the effects of resveratrol （RV） in reprogramming mouse embryonic fibroblasts （MEFs） into induced pluripotent stem cells （iPSCs） and the related mechanism. METHODS： Primary MEFs were i...OBJECTIVE： To investigate the effects of resveratrol （RV） in reprogramming mouse embryonic fibroblasts （MEFs） into induced pluripotent stem cells （iPSCs） and the related mechanism. METHODS： Primary MEFs were isolated from E13.5 embryos and used within three passages. Retroviruses expressing Sox2 and Oct4 were produced by transfecting GP2-293t cells with recombinant plasmids murine stern cell virus （MSCV）-Sox2 and MSCV-Oct4. Supernatants containing retroviruses were obtained after 48-hour transfection and MEFs were then infected. Different concentrations （0, 5, 10 and 20 IJmol/L） of RV were added to embryonic stem cell （ESC） medium to culture MEFs 48 h post-infection, iPSC clones emerged and were further cultured. Expression of pluripotent markers of iPSCs was identified by cell immunofluorescence and reverse transcription-polymerase chain reaction. Both cytotoxicity and cell proliferation were assayed by Western blot analysis after RV was added into ESC medium. The ultrastructure change of mitochondria was observed by electron microscopy. RESULTS： More than 2.9-fold and 1.3-fold increases in colony number were observed by treatment with RV at 5 and 10 pmol/L, respectively. The reprogramming efficiency was significantly decreased by treatment with 20 pmol/L RV. The proliferation effect on MEFs or MEFs infected by two factors Sox2/Oct4 （2 factors-MEFs, 2F-MEFs） was investigated after RV treatment. At 20 pmol/L RV, induced cell apoptosis and proliferation inhibition were more obvious than those of 5 and 10 IJmol/L treatments. Clones were selected from the 10 pmol/L RV-treated group and cultured. Green fluorescent protein expression from one typical clone was silenced one month later which expressed ESC-associated marker genes Gdf3, Nanog, Ecatl, Fgf4 and Foxd3. Electron transmission microscope showed obvious cavitations in mitochondria. The expression of hypoxia-inducible factor-la was up-regulated when 2F-MEFs were treated with RV compared to the control group. CONCLUSION： RV improved the efficiency of reprogramming 2F-MEFs into iPSCs at low and moderate concentrations （5 and 10 pmol/L）. The effect of 10 pmol/L RV on reprogramming was much greater than that of 5 pmol/L RV. However, high concentration of RV （20 pmol/L） led to more severe cavitations in mitochondria and caused cytotoxic effects. Taken together, these findinqs suqclest that RV mimics hypoxia in cells and promotes reprogramming at a low concentration.展开更多
BACKGROUND Today,biological fixation of uncemented press-fit acetabular components plays an important role in total hip arthroplasty.Long-term stable fixation of these implants depends on the osseointegration of the a...BACKGROUND Today,biological fixation of uncemented press-fit acetabular components plays an important role in total hip arthroplasty.Long-term stable fixation of these implants depends on the osseointegration of the acetabular cup bone tissue into the acetabular cup implant,and their ability to withstand functional loads.AIM To compare the strength of bone-implant osseointegration of four types of porous metal implants in normal and osteoporotic bone in rabbits.METHODS The study was performed in 50 female California rabbits divided into nonovariectomized(non-OVX)and ovariectomized groups(OVX)at 6 mo of age.Rabbits were sacrificed 8 wk after the implantation of four biomaterials[TTM,CONCELOC,Zimmer Biomet's Trabecular Metal(TANTALUM),and ATLANT]in a 5-mm diameter defect created in the left femur.A biomechanical evaluation of the femur was carried out by testing implant breakout force.The force was gradually increased until complete detachment of the implant from the bone occurred.RESULTS The breakout force needed for implant detachment was significantly higher in the non-OVX group,compared with the OVX group for all implants(TANTALUM,194.7±6.1 N vs 181.3±2.8 N;P=0.005;CONCELOC,190.8±3.6 N vs 180.9±6.6 N;P=0.019;TTM,186.3±1.8 N vs 172.0 N±11.0 N;P=0.043;and ATLANT,104.9±7.0 N vs 78.9 N±4.5 N;P=0.001).In the OVX group,The breakout forces in TANTALUM,TTM,and CONCELOC did not differ significantly(P=0.066).The breakout force for ATLANT in the OVX group was lower by a factor of 2.3 compared with TANTALUM and CONCELOC,and by 2.2 compared with TTM(P=0.001).In the non-OVX group,the breakout force for ATLANT was significantly different from all other implants,with a reduction in fixation strength by a factor of 1.9(P=0.001).CONCLUSION TANTALUM,TTM,and CONCELOC had equal bone-implant osseointegration in healthy and in osteoporotic bone.ATLANT had significantly decreased osseointegration(P=0.001)in healthy and in osteoporotic bone.展开更多
BACKGROUND Multipotent bone marrow stromal cells(BMSCs)are adult stem cells that form functional osteoblasts and play a critical role in bone remodeling.During aging,an increase in bone loss and reduction in structura...BACKGROUND Multipotent bone marrow stromal cells(BMSCs)are adult stem cells that form functional osteoblasts and play a critical role in bone remodeling.During aging,an increase in bone loss and reduction in structural integrity lead to osteoporosis and result in an increased risk of fracture.We examined age-dependent histological changes in murine vertebrae and uncovered that bone loss begins as early as the age of 1 mo.AIM To identify the functional alterations and transcriptomic dynamics of BMSCs during early bone loss.METHODS We collected BMSCs from mice at early to middle ages and compared their selfrenewal and differentiation potential.Subsequently,we obtained the transcriptomic profiles of BMSCs at 1 mo,3 mo,and 7 mo.RESULTS The colony-forming and osteogenic commitment capacity showed a comparable finding that decreased at the age of 1 mo.The transcriptomic analysis showed the enrichment of osteoblastic regulation genes at 1 mo and loss of osteogenic features at 3 mo.The BMSCs at 7 mo showed enrichment of adipogenic and DNA repair features.Moreover,we demonstrated that the WNT and MAPK signaling pathways were upregulated at 1 mo,followed by increased pro-inflammatory and apoptotic features.CONCLUSION Our study uncovered the cellular and molecular dynamics of bone aging in mice and demonstrated the contribution of BMSCs to the early stage of age-related bone loss.展开更多
BACKGROUND Total hip arthroplasty is a common surgical treatment for elderly patients with osteoporosis,particularly in postmenopausal women.In such cases,highly porous acetabular components are a favorable option in ...BACKGROUND Total hip arthroplasty is a common surgical treatment for elderly patients with osteoporosis,particularly in postmenopausal women.In such cases,highly porous acetabular components are a favorable option in achieving osseointegration.However,further discussion is needed if use of such acetabular components is justified under the condition of normal bone mass.AIM To determine the features of osseointegration of two different types of titanium implants[3-dimensional(3D)-printed and plasma-coated titanium implants]in bone tissue of a distal metaphysis in a rat femur model.METHODS This study was performed on 20 white male laboratory rats weighing 300-350 g aged 6 mo.Rats were divided into two groups of 10 animals,which had two different types of implants were inserted into a hole defect(2×3 mm)in the distal metaphysis of the femur:GroupⅠ:3D-printed titanium implant(highly porous);GroupⅡ:Plasma-coated titanium implant.After 45 and 90 d following surgery,the rats were sacrificed,and their implanted femurs were extracted for histological examination.The relative perimeter(%)of bone trabeculae[bone-implant contact(BIC%)]and bone marrow surrounding the titanium implants was measured.RESULTS Trabecular bone tissue was formed on the 45th day after implantation around the implants regardless of their type.45 d after surgery,group I(3D-printed titanium implant)and groupⅡ(plasma-coated titanium implant)did not differ in BIC%(83.51±8.5 vs 84.12±1.73;P=0.838).After 90 d,the BIC%was higher in group I(87.04±6.99 vs 81.24±7.62;P=0.049),compared to groupⅡ.The relative perimeter of the bone marrow after 45 d did not differ between groups and was 16.49%±8.58%for groupⅠ,and 15.88%±1.73%for groupⅡ.Futhermore,after 90 d,in groupⅠthe relative perimeter of bone marrow was 1.4 times smaller(12.96±6.99 vs 18.76±7.62;P=0.049)compared to the relative perimeter of bone marrow in groupⅡ.CONCLUSION The use of a highly porous titanium implant,manufactured with 3D printing,for acetabular components provides increased osseointegration compared to a plasma-coated titanium implant.展开更多
To date, it remains poorly understood whether astrocytes can be easily reprogrammed into neurons. Mashl and Brn2 have been previously shown to cooperate to reprogram fibroblasts into neurons. In this study, we examine...To date, it remains poorly understood whether astrocytes can be easily reprogrammed into neurons. Mashl and Brn2 have been previously shown to cooperate to reprogram fibroblasts into neurons. In this study, we examined astrocytes from 2-month-old Sprague-Dawley rats, and found that Brn2 was expressed, but Mashl was not detectable. Thus, we hypothesized that Mashl alone could be used to reprogram astrocytes into neurons. We transfected a recombinant MSCV-MASH1 plasmid into astrocytes for 72 hours, and saw that all cells expressed Mashl. One week later, we observed the changes in morphology of astrocytes, which showed typical neuro- nal characteristics. Moreover, β-tubulin expression levels were significantly higher in astrocytes expressing Mashl than in control cells. These results indicate that Mashl alone can reprogram astrocytes into neurons.展开更多
Purpose： Up to date, some approaches retarding the flow of cerebrospinal fluid （CSF） could be regarded as direct applications of the fluid mechanics （Poiseuille＇s law）. However, there is a lack of the research o...Purpose： Up to date, some approaches retarding the flow of cerebrospinal fluid （CSF） could be regarded as direct applications of the fluid mechanics （Poiseuille＇s law）. However, there is a lack of the research on the efficacy of subfascial drainage for management of CSF leak after spine surgery based on the law. This is a prospective and comparative study on suhfascial drainage for CSE Methods： Every four months in the three years from January 2010 to December 2012, the patients were enrolled respectively in Group A, Group B and Group C, in which, the drainage tube was discontinued within postoperative 3-4 days, 5-6 days, 7-10 days. Results and complications of postoperative CSF leak were investigated, and mean wound healing time （MWHT） of the three groups was compared. Results： A total of 108 cases （Group A/B/C：35/32/41） of CSF leak following posterior spine surgery were admitted to Tianjin Union Medicine Center, and 92 cases have been followed up for more than 1 year （follow-up rate of 85.2%）. Preoperative demographics were similar among the 3 groups. In Group A, 7 patients developed CSI： leak through the wound （CSFLW）, of which 5 cases had to undergo reoperation. One case in Group A was confirmed to have pseudomeningocele at the 1st month after surgery. The MWHT was （16.6 ± 3.6） days. In Group B, 3 patients developed CSFLW and cured by reoperation, in which 1 case of superficial infection recovered well after reoperation. MWHT was （11.4 ± 2.2） days. In Group C, CSFLW was not found and MWHT was （10.1 ± 2.9） days. The differences of MWHT among Groups A, B and C were statistically significant.Conclusion： Postoperative subfascial drainage, which is used to decrease the subfascial space pressure （P2）, would help wound healing. When it is placed for more than 7 days, the wound resistance （Rw） would be strong enough to withstand the suharachnoid pressure （P1）. Meanwhile, the power trans- duction in a sequence of Rw 〉 P2〉P1 will indirectly retard CSF leak at the durotomy site and accordingly facilitate the healing of damaged spinal dura mater.展开更多
OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.DATA SOURCES: Key terms were "stroke","brain diseases","brain injur...OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.DATA SOURCES: Key terms were "stroke","brain diseases","brain injuries","brain hemorrhage, traumatic","acute brain injury","dizocilpine maleate","dizocilpine","MK-801","MK801","rat","rats","rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform(VJIP) and SinoMed databases were searched from their inception dates to March 2018.DATA SELECTION: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments.OUTCOME MEASURES: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury.RESULTS: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P < 0.00001) and degree of cerebral edema(5 studies, n = 75, MD =-1.21, 95% CI:-1.50 to-0.91;P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test(2 studies, n = 60, MD =-10.88, 95% CI:-20.75 to-1.00;P = 0.03) and neurological function 24 hours after brain injury(11 studies, n = 335, MD =-1.04, 95% CI:-1.47 to-0.60;P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P = 0.004). Further network analysis showed that 0–1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model.CONCLUSION: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.展开更多
The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influe...The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.展开更多
Kidney governing bone theory plays an important role in treating bone metabolic disease such as osteoporosis, and many tonifying kidney prescriptions/herbs are widely used in Traditional Chinese Medicine(TCM). However...Kidney governing bone theory plays an important role in treating bone metabolic disease such as osteoporosis, and many tonifying kidney prescriptions/herbs are widely used in Traditional Chinese Medicine(TCM). However, the exact biological basis of kidney governing bone theory in the context of new advances in biology is still not fully established. In this paper, the content of kidney governing bone theory in biology has been fully demonstrated from different aspects. We first propose that bone and kidney mutually affect each other in pathology and physiology, particularly through homeostasis of calcium, phosphorus and fibroblast growth factor-23(FGF-23). Next, we identify that tonifying kidney prescriptions/herbs exert bone protective effects, thus treating osteoporosis by regulating bone formation and bone resorption.Furthermore, the exact molecular mechanisms of tonifying kidney prescriptions, herbs and their effective components in treating osteoporosis have been systematically reviewed. Finally, we come into the conclusion that kidney regulating bone mineral homeostasis, bone protective effects of tonifying kidney herbs and regulatory effects on bone homeostasis are all the manifestations of kidney governing bone theory.Therefore, the new insights into kidney governing bone theory in biology will promote the development of clinical practices, and drugs discovery in treating osteoporosis.展开更多
Qi She Pill(QSP)is a traditional Chinese medicine(TCM)prescription that has been used in treating cervical spondylosis radiculopathy for many years.In this study,a simple and sensitive method using ultra-high-performa...Qi She Pill(QSP)is a traditional Chinese medicine(TCM)prescription that has been used in treating cervical spondylosis radiculopathy for many years.In this study,a simple and sensitive method using ultra-high-performance liquid chromatography–tandem mass spectrometry(UHPLC–MS/MS)on a reverse-phase C18 column was developed for the simultaneous determination of the 19 major components in QSP.We found that the optimum mobile phase for gradient elution was 0.1% formic acid and methanol.The correlation coefficients of all calibration curves were greater than 0.99.Recoveries measured at three concentration levels varied from 95.43%to 102.35%.Relative standard deviations of intra-and inter-day precisions were less than 4.45%.After successfully validating our method,we then applied it to the quantification of 19 components in QSP products to show that this method provides a new standard in quality assessment of TCM prescriptions containing multiple bioactive components.展开更多
Yin-Yang theory plays critical role in traditional Chinese medicine(TCM) science. However, there are many competing interpretations of YinYang theory in the context with the development in biology, and no consensus ha...Yin-Yang theory plays critical role in traditional Chinese medicine(TCM) science. However, there are many competing interpretations of YinYang theory in the context with the development in biology, and no consensus has been established. Here we first propose that osteoblast should be regarded as Yin, while osteoclast should be considered as Yang in bone remodeling compartment(BRC). Our conceptions are consistent with the following key findings: 1)osteoblast and osteoclast both derive from the embryonic ectoderm; 2)osteoblast and osteoclast work collaboratively in BRC to maintain bone homeostasis; 3)the activities of osteoblast and osteoclast are coupled to remain dynamic balance;4)osteoblast and osteoclast exert their function in ceaseless successions. Moreover, we argue that Yin-Yang relationships exist between osteoblast and osteoclast: osteoblast secretes the receptor activator for nuclear factor-κB ligand(RANKL) and the monocyte/macrophage colony-stimulating factor(M-CSF) and osteoprotegerin(OPG) to positively or negatively regulate osteoclast differentiation and function.Meanwile, osteoclast and bone resorption in turn release cytokines, such as transforming growth factor-β(TGF-β), insulin-like growth factor-1(IGF-1) from bone matrix, to regulate osteoblast differentiation and function. Next, the unlimited division of Yin-Yang can be applied to divide sublevel of Yin-Yang inside osteoblast or osteoclast. Finally, Yin-Yang relationship of osteoblast and osteoclast is relative. Therefore, we come into the conclusion that the relationships between osteoblast and osteoclast as established in contemporary biology reflect the classic Yin-Yang in bone remodeling. The new Yin-Yang concepts of osteoblast and osteoclast may strengthen basic theory and clinical practice in TCM.展开更多
Objective：To summarize and critically assess the efficacy of Eastern and Western manipulative therapies for the treatment of neck pain in adults. Methods：A search of Pub Med/MEDLINE, the Cochrane Central Register of...Objective：To summarize and critically assess the efficacy of Eastern and Western manipulative therapies for the treatment of neck pain in adults. Methods：A search of Pub Med/MEDLINE, the Cochrane Central Register of Controlled Trials, Clinical Trials.gov, EMBASE, etc. from their inception date to January 2014 with Chinese, Japanese, and Korean databases. Two reviewers independently selected randomized controlled trials（RCTs） with negative control or blank control, extracted data and assessed methodological quality. Meta-analysis and levels of evidence were performed by Revman5.1 and Grades of Recommendations Assessment, Development and Evaluation（GRADE） approach. Results：Nineteen clinical trials with adequate randomization were included in this review, 11 of them had a low risk of bias. The primary outcome for shortterm pain had no significant differences, however, the secondary outcome, only the Numerical Pain Rating Scale（NPRS） score of intermediate-term [n=916, pooled mean differences（MD） =–0.29, P=0.02], the Neck Disability Index（NDI） score of short-term（n=1,145, pooled MD=–2.10, P〈0.01）, and intermediate-term（n=987, pooled MD=–1.45, P=0.01） were significantly reduced with moderate quality evidence. However, it supported the minimally clinically important difference（MCID） of the Visual Analogue Scale and NPRS pain score to be 13 mm, while NDI was 3.5 points. The meta-analysis only suggested a trend in favor of manipulative therapy rather than clinical significance. Conclusions：The results do not support the existing evidences for the clinical value of Eastern or Western manipulative therapy for neck pain of short-term follow-up according to MCIDs. The limitations of our review related to blinding, allocation concealment and small sample size.展开更多
To the Editor:Osteosarcoma(OS),a disease seriously endangering the health of young people,is the eighth most common primary malignant bone tumor affecting children and adolescents.Typically occurring in the metaphysis...To the Editor:Osteosarcoma(OS),a disease seriously endangering the health of young people,is the eighth most common primary malignant bone tumor affecting children and adolescents.Typically occurring in the metaphysis of long tubular bone,OS develops from mesenchymal cells and accounts for 20%of primary bone tumors.About 70%to 80%of patients are 8 to 9 years.展开更多
Objective: To analyze the gene expression profile of degenerated cervical intervertebral disc of Sprague Dawley rats on a large scale.Methods: Degenerated models of Sprague Dawley rats of 9 months old (degeneration gr...Objective: To analyze the gene expression profile of degenerated cervical intervertebral disc of Sprague Dawley rats on a large scale.Methods: Degenerated models of Sprague Dawley rats of 9 months old (degeneration group, n=9) and normal Sprague Dawley rats of 3 months old (control group, n=9) were prepared, respectively. mRNA was obtained from the cervical intervertebral disc of rats in both groups, respectively, and then labelled by Cy5 and Cy3 fluorescence respectively after reverse transcription to obtain intervertebral disc cDNA probes. cDNA probes were hybridized with BiostarR-40s gene expression profile chips and scanned by laser scanner. The results were treated with portrait analysis, standardization management, and ratio analysis with softwares.Results: Compared with the rats in the control group, (9.6)% (381 pieces in total) gene expression changed obviously in the rats in the degeneration group, among which, the gene expression quantities of 171 pieces increased significantly (r=the ratio of the degeneration group to the control group >(2.0)), 52 pieces of which had certain function. While the gene expression quantities of 211 pieces decreased significantly (r<(0.5)), 41 pieces of which had certain function.Conclusions: Gene chip technology can be used to analyze the gene expression profile of degenerated intervertebral disc of rats in parallel, in quantity and on a large scale, which helps to testify the representative genes and protein expression, and plays an important role in clarifying the pathogenesis of degenerated intervertebral disc.展开更多
Objective: To summarize and critically assess the inhibitory effects of Chinese herbal medicine(CHM) on tumor volume and tumor weight for the treatment of osteosarcoma(OS) in mouse models. Methods:PubMed, Embase, Web ...Objective: To summarize and critically assess the inhibitory effects of Chinese herbal medicine(CHM) on tumor volume and tumor weight for the treatment of osteosarcoma(OS) in mouse models. Methods:PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database(CNKI), Wanfang Database, VIP Database, and Chinese BioMedical(CBM) were searched since their inception dates to March10, 2016. Two reviewers independently selected the controlled studies estimating effects of CHM on mouse OS by administration in vivo. A pair-wise meta-analysis was performed. Twenty-five studies with adequate randomization were included in the systematic review. Results: CHM may signi?cantly inhibit OS growth in mice, as assessed using the tumor weight [20 studies, n=443; 290 for CHM and 153 for the control; pooled mean difference(MD)=–2.90; 95% confidence interval(CI): –3.50 to –2.31; P<0.01], tumor volume(16 studies, n=382; 257 for CHM and 125 for the control; pooled MD =–2.57; 95% CI: –3.33 to –1.80; P<0.01) and tumor growth inhibition rate. Conclusion: CHM could significantly inhibit the growth of OS in mouse models,which might be supportive for the design of preclinical and clinical trials in future.展开更多
The systematicness of phenomics and Traditional Chinese Medicine(TCM)enable these two disciplines to interlink with each other.This article discussed the similarity in theory and application between TCM and phenomics ...The systematicness of phenomics and Traditional Chinese Medicine(TCM)enable these two disciplines to interlink with each other.This article discussed the similarity in theory and application between TCM and phenomics and illustrates their respective advantages in diagnosis and treatment of diseases,forming a new discipline eventually.Chinese medicine phe-nomics(Chinmedphenomics)is built on classic TCM,combined with phenomics technology,and the development of which needs the mega cohort with TCM syndrome and the characteristics of precision medicine as well as multi-disciplinary coop-eration,which is personalized,precise and promising,providing unique scientific insights into understanding human health.展开更多
基金National Natural Science Foundation of China(Grant No.81273777,81102606,81072831)the National Basic Re search Program of China(Grant No.2010CB530400)the Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT,IRT1270)
文摘The inflammatory cytokine interleukin-1 beta （IL-1β） plays a key role in the process of intervertebral disc degenera- tion （IVDD）. In the present study, we aimed to evaluate the effect of pharmaco-serum of ＂Taoren-Honghua-herb pair＂ on IL-1β- induced chondrocyte degeneration in vitro. Taoren （Semen persicae） and Honghua （Safflower carthamus） were administered to the rats, and the pharmaco-serum was collected and prepared. Chondrocytes of the third passage, isolated from the rat＇s vertebral endplates, were treated by standard medium only （Group NC）, IL-1β （Group IL） or combination of IL-1β and pharmaco-serum （Group TRHH）. Cell proliferation and apoptosis were determined, and the expression of aggrecan, Col2ul, Coll0ul, IL-6 and SOX9 at the mRNA level in chondrocytes was quantified by real-time PCR. Immunohistochemistry staining of type II and X collagen and Safranine O staining were also used to evaluate the chondrocytes. Compared with the Group NC, IL-1β treatment inhibited the cell proliferation and induced the cell apoptosis （P〈0.05）, and the expression of aggrecan, Col2αl and SOX9 at the mRNA level was down-regulated. In contrast, the expression of Coll0ul and IL-6 was up-regulated after IL-1β treatment （P〈0.05）. Meanwhile, the immune-staining of type II collagen and Safranine O staining were decreased, while the staining of type X collagen was increased. Compared with the Group IL, cell proliferation was increased, and apoptosis of chondrocytes was decreased when cells were treated with the pharmaco-semm of TRHH-herb pair （P〈0.05）. The expression of aggrecan, Col2cd and SOX9 at the mRNA level was up-regulated, while that of Coll0cd and IL-6 was down-regulated （P〈0.05）. Saffanine O staining also showed increased positive staining （P〈0.05）. Taken together, the treatment of pharmaco-serum of TRHH-herb pair could prevent endplate chondrocyte degeneration induced by IL-1β.
文摘Intervertebral disc （IVD） degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about how mechanical stress regulates nucleus notochordal （NC） cells to maintain IVD homeostasis. Here we report that mechanical stress can result in excessive integrin αvβ6-mediated activation of transforming growth factor beta （TGFβ）, decreased NC cell vacuoles, and increased matrix proteoglycan production, and results in degenerative disc disease （DDD）. Knockout of TGFβ type II receptor （TβRII） or integrin αv in the NC cells inhibited functional activity of postnatal NC cells and also resulted in DDD under mechanical loading. Administration of RGD peptide, TGFβ, and αvβ6-neutralizing antibodies attenuated IVD degeneration. Thus, integrin-mediated activation of TGFβ plays a critical role in mechanical signaling transduction to regulate IVD cell function and homeostasis. Manipulation of this signaling pathway may be a potential therapeutic target to modify DDD.
基金supported by the National Natural Science Foundation of China,No.81704096,81603635,81873317(to MY,JY,XJC)Shanghai Science and Technology Commission-Key Project of Traditional Chinese Medicine,No.16401970100(to YJW)+4 种基金the Shanghai Traditional Chinese Medicine Medical Center of Chronic Disease of China,No.2017ZZ01010(to YJW)the National Thirteenth Five-Year Science and Technology Major Special Project for New Drug Innovation and Development of China,No.2017ZX09304001(to YJW)the Program for Innovative Research Team of Ministry of Science and Technology of China,No.2015RA4002(to YJW)the “Innovation Team” Development Projects of China,No.IRT1270(to YJW)the Three Years Action to Accelerate the Development of Traditional Chinese Medicine Plan of China,No.ZY(2018-2020)-CCCX-3003(to YJW)
文摘Objective:Studies have shown that docosahexaenoic acid(DHA)has a beneficial effect in the treatment of spinal cord injury.A meta-analysis was used to study the effect of DHA on the neurological recovery in the rat spinal cord injury model,and the relationship between the recovery of motor function after spinal cord injury and the time and method of administration and the dose of DHA.Data source:Published studies on the effect of DHA on spinal cord injury animal models from seven databases were searched from their inception to January 2019,including PubMed,MEDLINE,EMBASE,the China National Knowledge Infrastructure,Wanfang,VIP,and SinoMed databases.The search terms included“spinal cord injury”“docosahexaenoic acid”,and“rats”.Data selection:Studies that evaluated the influence of DHA in rat models of spinal cord injury for locomotor functional recovery were included.The intervention group included any form of DHA treatment and the control group included treatment with normal saline,vehicle solution or no treatment.The Systematic Review Centre for Laboratory animal Experimentation’s risk of bias assessment tool was used for the quality assessment of the included studies.Literature inclusion,quality evaluation and data extraction were performed by two researchers.Meta-analysis was then conducted on all studies that met the inclusion criteria.Statistical analysis was performed on the data using RevMan 5.1.2.software.Outcome measures:The primary outcome measure was the score on the Basso,Beattie,and Bresnahan scale.Secondary outcome measures were the sloping plate test,balance beam test,stair test and grid exploration test.Results:A total of 12 related studies were included,3 of which were of higher quality and the remaining 9 were of lower quality.The highest mean Basso,Beattie,and Bresnahan scale score occurred at 42 days after DHA treatment in spinal cord injury rats.At 21 days after treatment,the mean difference in Basso,Beattie,Bresnahan scores between the DHA group and the control group was the most significant(pooled MD=4.14;95%CI=3.58–4.70;P<0.00001).In the subgroup analysis,improvement in the Basso,Beattie,and Bresnahan scale score was more significant in rats administered DHA intravenously(pooled MD=2.74;95%CI=1.41–4.07;P<0.0001)and subcutaneously(pooled MD=2.99;95%CI=2.29–3.69;P<0.00001)than in the groups administered DHA orally(pooled MD=3.04;95%CI=–1.01 to 7.09;P=0.14).Intravenous injection of DHA at 250 nmol/kg(pooled MD=2.94;95%CI=2.47–3.41;P<0.00001]and 1000 nmol/kg[pooled MD=3.60;95%CI=2.66–4.54;P<0.00001)significantly improved the Basso,Beattie,and Bresnahan scale score in rats and promoted the recovery of motor function.Conclusion:DHA can promote motor functional recovery after spinal cord injury in rats.The administration of DHA by intravenous or subcutaneous injection is more effective than oral administration of DHA.Intravenous injection of DHA at doses of 250 nmol/kg or 1000 nmol/kg is beneficial.Because of the small number and the low quality of the included studies,more high-quality research is needed in future to substantiate the results.
基金supported by the National Basic Research Program of China(973 Program,No.2010CB530400)the Key Project of National Natural Science Foundation of China(No.30930111)+3 种基金Changjiang Scholar Chair Professor Project(Teach people(2009) 17)Shanghai Education Innovation Project(No.08YZ56)"Shu Guang" project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation(No.10GG20)Shanghai University Innovation Team Programmer(Shanghai Education Commission, Division 6(2009))
文摘OBJECTIVE： To investigate the effects of resveratrol （RV） in reprogramming mouse embryonic fibroblasts （MEFs） into induced pluripotent stem cells （iPSCs） and the related mechanism. METHODS： Primary MEFs were isolated from E13.5 embryos and used within three passages. Retroviruses expressing Sox2 and Oct4 were produced by transfecting GP2-293t cells with recombinant plasmids murine stern cell virus （MSCV）-Sox2 and MSCV-Oct4. Supernatants containing retroviruses were obtained after 48-hour transfection and MEFs were then infected. Different concentrations （0, 5, 10 and 20 IJmol/L） of RV were added to embryonic stem cell （ESC） medium to culture MEFs 48 h post-infection, iPSC clones emerged and were further cultured. Expression of pluripotent markers of iPSCs was identified by cell immunofluorescence and reverse transcription-polymerase chain reaction. Both cytotoxicity and cell proliferation were assayed by Western blot analysis after RV was added into ESC medium. The ultrastructure change of mitochondria was observed by electron microscopy. RESULTS： More than 2.9-fold and 1.3-fold increases in colony number were observed by treatment with RV at 5 and 10 pmol/L, respectively. The reprogramming efficiency was significantly decreased by treatment with 20 pmol/L RV. The proliferation effect on MEFs or MEFs infected by two factors Sox2/Oct4 （2 factors-MEFs, 2F-MEFs） was investigated after RV treatment. At 20 pmol/L RV, induced cell apoptosis and proliferation inhibition were more obvious than those of 5 and 10 IJmol/L treatments. Clones were selected from the 10 pmol/L RV-treated group and cultured. Green fluorescent protein expression from one typical clone was silenced one month later which expressed ESC-associated marker genes Gdf3, Nanog, Ecatl, Fgf4 and Foxd3. Electron transmission microscope showed obvious cavitations in mitochondria. The expression of hypoxia-inducible factor-la was up-regulated when 2F-MEFs were treated with RV compared to the control group. CONCLUSION： RV improved the efficiency of reprogramming 2F-MEFs into iPSCs at low and moderate concentrations （5 and 10 pmol/L）. The effect of 10 pmol/L RV on reprogramming was much greater than that of 5 pmol/L RV. However, high concentration of RV （20 pmol/L） led to more severe cavitations in mitochondria and caused cytotoxic effects. Taken together, these findinqs suqclest that RV mimics hypoxia in cells and promotes reprogramming at a low concentration.
文摘BACKGROUND Today,biological fixation of uncemented press-fit acetabular components plays an important role in total hip arthroplasty.Long-term stable fixation of these implants depends on the osseointegration of the acetabular cup bone tissue into the acetabular cup implant,and their ability to withstand functional loads.AIM To compare the strength of bone-implant osseointegration of four types of porous metal implants in normal and osteoporotic bone in rabbits.METHODS The study was performed in 50 female California rabbits divided into nonovariectomized(non-OVX)and ovariectomized groups(OVX)at 6 mo of age.Rabbits were sacrificed 8 wk after the implantation of four biomaterials[TTM,CONCELOC,Zimmer Biomet's Trabecular Metal(TANTALUM),and ATLANT]in a 5-mm diameter defect created in the left femur.A biomechanical evaluation of the femur was carried out by testing implant breakout force.The force was gradually increased until complete detachment of the implant from the bone occurred.RESULTS The breakout force needed for implant detachment was significantly higher in the non-OVX group,compared with the OVX group for all implants(TANTALUM,194.7±6.1 N vs 181.3±2.8 N;P=0.005;CONCELOC,190.8±3.6 N vs 180.9±6.6 N;P=0.019;TTM,186.3±1.8 N vs 172.0 N±11.0 N;P=0.043;and ATLANT,104.9±7.0 N vs 78.9 N±4.5 N;P=0.001).In the OVX group,The breakout forces in TANTALUM,TTM,and CONCELOC did not differ significantly(P=0.066).The breakout force for ATLANT in the OVX group was lower by a factor of 2.3 compared with TANTALUM and CONCELOC,and by 2.2 compared with TTM(P=0.001).In the non-OVX group,the breakout force for ATLANT was significantly different from all other implants,with a reduction in fixation strength by a factor of 1.9(P=0.001).CONCLUSION TANTALUM,TTM,and CONCELOC had equal bone-implant osseointegration in healthy and in osteoporotic bone.ATLANT had significantly decreased osseointegration(P=0.001)in healthy and in osteoporotic bone.
基金Supported by the National Natural Science Foundation of China,No.81573992.
文摘BACKGROUND Multipotent bone marrow stromal cells(BMSCs)are adult stem cells that form functional osteoblasts and play a critical role in bone remodeling.During aging,an increase in bone loss and reduction in structural integrity lead to osteoporosis and result in an increased risk of fracture.We examined age-dependent histological changes in murine vertebrae and uncovered that bone loss begins as early as the age of 1 mo.AIM To identify the functional alterations and transcriptomic dynamics of BMSCs during early bone loss.METHODS We collected BMSCs from mice at early to middle ages and compared their selfrenewal and differentiation potential.Subsequently,we obtained the transcriptomic profiles of BMSCs at 1 mo,3 mo,and 7 mo.RESULTS The colony-forming and osteogenic commitment capacity showed a comparable finding that decreased at the age of 1 mo.The transcriptomic analysis showed the enrichment of osteoblastic regulation genes at 1 mo and loss of osteogenic features at 3 mo.The BMSCs at 7 mo showed enrichment of adipogenic and DNA repair features.Moreover,we demonstrated that the WNT and MAPK signaling pathways were upregulated at 1 mo,followed by increased pro-inflammatory and apoptotic features.CONCLUSION Our study uncovered the cellular and molecular dynamics of bone aging in mice and demonstrated the contribution of BMSCs to the early stage of age-related bone loss.
文摘BACKGROUND Total hip arthroplasty is a common surgical treatment for elderly patients with osteoporosis,particularly in postmenopausal women.In such cases,highly porous acetabular components are a favorable option in achieving osseointegration.However,further discussion is needed if use of such acetabular components is justified under the condition of normal bone mass.AIM To determine the features of osseointegration of two different types of titanium implants[3-dimensional(3D)-printed and plasma-coated titanium implants]in bone tissue of a distal metaphysis in a rat femur model.METHODS This study was performed on 20 white male laboratory rats weighing 300-350 g aged 6 mo.Rats were divided into two groups of 10 animals,which had two different types of implants were inserted into a hole defect(2×3 mm)in the distal metaphysis of the femur:GroupⅠ:3D-printed titanium implant(highly porous);GroupⅡ:Plasma-coated titanium implant.After 45 and 90 d following surgery,the rats were sacrificed,and their implanted femurs were extracted for histological examination.The relative perimeter(%)of bone trabeculae[bone-implant contact(BIC%)]and bone marrow surrounding the titanium implants was measured.RESULTS Trabecular bone tissue was formed on the 45th day after implantation around the implants regardless of their type.45 d after surgery,group I(3D-printed titanium implant)and groupⅡ(plasma-coated titanium implant)did not differ in BIC%(83.51±8.5 vs 84.12±1.73;P=0.838).After 90 d,the BIC%was higher in group I(87.04±6.99 vs 81.24±7.62;P=0.049),compared to groupⅡ.The relative perimeter of the bone marrow after 45 d did not differ between groups and was 16.49%±8.58%for groupⅠ,and 15.88%±1.73%for groupⅡ.Futhermore,after 90 d,in groupⅠthe relative perimeter of bone marrow was 1.4 times smaller(12.96±6.99 vs 18.76±7.62;P=0.049)compared to the relative perimeter of bone marrow in groupⅡ.CONCLUSION The use of a highly porous titanium implant,manufactured with 3D printing,for acetabular components provides increased osseointegration compared to a plasma-coated titanium implant.
基金supported by the National Basic Research Program of China(973 Program),No.2010CB530400the Key Project of National Natural Science Foundation of China,No.30930111
文摘To date, it remains poorly understood whether astrocytes can be easily reprogrammed into neurons. Mashl and Brn2 have been previously shown to cooperate to reprogram fibroblasts into neurons. In this study, we examined astrocytes from 2-month-old Sprague-Dawley rats, and found that Brn2 was expressed, but Mashl was not detectable. Thus, we hypothesized that Mashl alone could be used to reprogram astrocytes into neurons. We transfected a recombinant MSCV-MASH1 plasmid into astrocytes for 72 hours, and saw that all cells expressed Mashl. One week later, we observed the changes in morphology of astrocytes, which showed typical neuro- nal characteristics. Moreover, β-tubulin expression levels were significantly higher in astrocytes expressing Mashl than in control cells. These results indicate that Mashl alone can reprogram astrocytes into neurons.
文摘Purpose： Up to date, some approaches retarding the flow of cerebrospinal fluid （CSF） could be regarded as direct applications of the fluid mechanics （Poiseuille＇s law）. However, there is a lack of the research on the efficacy of subfascial drainage for management of CSF leak after spine surgery based on the law. This is a prospective and comparative study on suhfascial drainage for CSE Methods： Every four months in the three years from January 2010 to December 2012, the patients were enrolled respectively in Group A, Group B and Group C, in which, the drainage tube was discontinued within postoperative 3-4 days, 5-6 days, 7-10 days. Results and complications of postoperative CSF leak were investigated, and mean wound healing time （MWHT） of the three groups was compared. Results： A total of 108 cases （Group A/B/C：35/32/41） of CSF leak following posterior spine surgery were admitted to Tianjin Union Medicine Center, and 92 cases have been followed up for more than 1 year （follow-up rate of 85.2%）. Preoperative demographics were similar among the 3 groups. In Group A, 7 patients developed CSI： leak through the wound （CSFLW）, of which 5 cases had to undergo reoperation. One case in Group A was confirmed to have pseudomeningocele at the 1st month after surgery. The MWHT was （16.6 ± 3.6） days. In Group B, 3 patients developed CSFLW and cured by reoperation, in which 1 case of superficial infection recovered well after reoperation. MWHT was （11.4 ± 2.2） days. In Group C, CSFLW was not found and MWHT was （10.1 ± 2.9） days. The differences of MWHT among Groups A, B and C were statistically significant.Conclusion： Postoperative subfascial drainage, which is used to decrease the subfascial space pressure （P2）, would help wound healing. When it is placed for more than 7 days, the wound resistance （Rw） would be strong enough to withstand the suharachnoid pressure （P1）. Meanwhile, the power trans- duction in a sequence of Rw 〉 P2〉P1 will indirectly retard CSF leak at the durotomy site and accordingly facilitate the healing of damaged spinal dura mater.
基金supported by the National Natural Science Foundation of China,No.81822050(to QQL),81873321(to HX),81673990(to QQL),81330085(to QS),81730107(to YJW)the Shanghai Municipal Health and Family Planning Commission TCM Research Project of China,No.2018JP014(to HX)+4 种基金the Three-Year Action Plan to Promote Clinical Skills and Clinical Innovation in Municipal Hospitals of China,No.16CR1017A(to YJW)the Shanghai Traditional Chinese Medicine Chronic Disease [Malignant Tumor,Bone Degenerative Disease] Clinical Medical Center of China,No.2017ZZ01010(to YJW)the National Ministry of Education Innovation Team of China,No.IRT1270(to YJW)the Innovation Team of Key Fields of the Ministry of Science and Technology of China,No.2015RA4002(to YJW)the Outstanding Principle Investigator Project of Guanghua Hospital,Changning District,Shanghai,China,No.2016-01(to QS),2016-06(to YJW)
文摘OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.DATA SOURCES: Key terms were "stroke","brain diseases","brain injuries","brain hemorrhage, traumatic","acute brain injury","dizocilpine maleate","dizocilpine","MK-801","MK801","rat","rats","rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform(VJIP) and SinoMed databases were searched from their inception dates to March 2018.DATA SELECTION: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments.OUTCOME MEASURES: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury.RESULTS: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P < 0.00001) and degree of cerebral edema(5 studies, n = 75, MD =-1.21, 95% CI:-1.50 to-0.91;P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test(2 studies, n = 60, MD =-10.88, 95% CI:-20.75 to-1.00;P = 0.03) and neurological function 24 hours after brain injury(11 studies, n = 335, MD =-1.04, 95% CI:-1.47 to-0.60;P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P = 0.004). Further network analysis showed that 0–1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model.CONCLUSION: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.
基金National Key Basic Research Program from MOST, China (Nos. 2016YFA0100801 and 2014CB964602)the National Natural Science Foundation of China (Grant Nos. 81330030, 31620103904 and 81650110524)+1 种基金the National Institutes of Health (NIH5R21NS095184-02)the "RNAseq on Single Cell and beyond Core "in the Developme ntal Disabilities Research Center (NIH5U54HD087101-02) at University of California Los Angeles.
文摘The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.
基金supported by grants from Shanghai Yangfan Program (15YF1412200)Longhua Medical Team Project (LYTD-23)+4 种基金Longhua natural science program (14YR03)the Independent Innovation Program Supported by Science and Technology Innovation of the "085" First-class Disciplines Construction of Shanghai University of TCM (085ZY1217)the National Natural Science foundation of major international cooperation projects (81220108027)the Program of Natural Science Foundation of China (81202708, 81072831, 81102605, 81102606, 81373667, 81102606, 81202708)the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT, IRT1270)
文摘Kidney governing bone theory plays an important role in treating bone metabolic disease such as osteoporosis, and many tonifying kidney prescriptions/herbs are widely used in Traditional Chinese Medicine(TCM). However, the exact biological basis of kidney governing bone theory in the context of new advances in biology is still not fully established. In this paper, the content of kidney governing bone theory in biology has been fully demonstrated from different aspects. We first propose that bone and kidney mutually affect each other in pathology and physiology, particularly through homeostasis of calcium, phosphorus and fibroblast growth factor-23(FGF-23). Next, we identify that tonifying kidney prescriptions/herbs exert bone protective effects, thus treating osteoporosis by regulating bone formation and bone resorption.Furthermore, the exact molecular mechanisms of tonifying kidney prescriptions, herbs and their effective components in treating osteoporosis have been systematically reviewed. Finally, we come into the conclusion that kidney regulating bone mineral homeostasis, bone protective effects of tonifying kidney herbs and regulatory effects on bone homeostasis are all the manifestations of kidney governing bone theory.Therefore, the new insights into kidney governing bone theory in biology will promote the development of clinical practices, and drugs discovery in treating osteoporosis.
基金This research was supported by the Key Discipline of Shanghai City Board of Education(No.J50302)Higher Specialized Research Fund for the Doctoral Program(No.20123107110007)+6 种基金Alliance Program-problem of bidding project(No.2012033)MOST“significant Drug Discovery”major science and technology“Twelve Five”Implementation Plan(2011ZX09302-006-04)Ministry of Education,“Innovative Research Team”(1RT1270)Ministry of Education Key Laboratory of Ministry(Education Technology(2009)98)Shanghai“most important”Clinical Center construction project,Shanghai University of Traditional Chinese Medicine“085 Project”class TCM Discipline Pro-ject“Boot Innovation Program”(085ZY1204)Shanghai Sci-ence and Technology Commission of modern medicine special(09dZ1977200)Shanghai university innovation team plans(Shanghai Branch Board of Education(2009)No.6).
文摘Qi She Pill(QSP)is a traditional Chinese medicine(TCM)prescription that has been used in treating cervical spondylosis radiculopathy for many years.In this study,a simple and sensitive method using ultra-high-performance liquid chromatography–tandem mass spectrometry(UHPLC–MS/MS)on a reverse-phase C18 column was developed for the simultaneous determination of the 19 major components in QSP.We found that the optimum mobile phase for gradient elution was 0.1% formic acid and methanol.The correlation coefficients of all calibration curves were greater than 0.99.Recoveries measured at three concentration levels varied from 95.43%to 102.35%.Relative standard deviations of intra-and inter-day precisions were less than 4.45%.After successfully validating our method,we then applied it to the quantification of 19 components in QSP products to show that this method provides a new standard in quality assessment of TCM prescriptions containing multiple bioactive components.
基金supported by grants from the National Basic Research Program of China(2010CB530400)the National Natural Science Foundation of major international cooperation projects(81220108027)+6 种基金the Program of Natural Science Foundation of China(81202708,81072831,81102605,81102606,81102851,81373667,81102606,81202708)the Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT,IRT1270)Shanghai Pujiang Program(12PJ1408100)Shanghai Yangfan Program(15YF1412200)Longhua Medical Team Project(LYTD-23,LYTD-08)Longhua natural science foundation(14YR03)Chinese Postdoctoral funds(2011M500620)
文摘Yin-Yang theory plays critical role in traditional Chinese medicine(TCM) science. However, there are many competing interpretations of YinYang theory in the context with the development in biology, and no consensus has been established. Here we first propose that osteoblast should be regarded as Yin, while osteoclast should be considered as Yang in bone remodeling compartment(BRC). Our conceptions are consistent with the following key findings: 1)osteoblast and osteoclast both derive from the embryonic ectoderm; 2)osteoblast and osteoclast work collaboratively in BRC to maintain bone homeostasis; 3)the activities of osteoblast and osteoclast are coupled to remain dynamic balance;4)osteoblast and osteoclast exert their function in ceaseless successions. Moreover, we argue that Yin-Yang relationships exist between osteoblast and osteoclast: osteoblast secretes the receptor activator for nuclear factor-κB ligand(RANKL) and the monocyte/macrophage colony-stimulating factor(M-CSF) and osteoprotegerin(OPG) to positively or negatively regulate osteoclast differentiation and function.Meanwile, osteoclast and bone resorption in turn release cytokines, such as transforming growth factor-β(TGF-β), insulin-like growth factor-1(IGF-1) from bone matrix, to regulate osteoblast differentiation and function. Next, the unlimited division of Yin-Yang can be applied to divide sublevel of Yin-Yang inside osteoblast or osteoclast. Finally, Yin-Yang relationship of osteoblast and osteoclast is relative. Therefore, we come into the conclusion that the relationships between osteoblast and osteoclast as established in contemporary biology reflect the classic Yin-Yang in bone remodeling. The new Yin-Yang concepts of osteoblast and osteoclast may strengthen basic theory and clinical practice in TCM.
基金Supported by the National Natural Science Foundation of China(No.81373666)Municipal Hospitals Cutting-Edge Technologies Emerging Joint Project(No.SHDC12013113)+3 种基金Municipal Science and Technology Commission of Shanghai Chinese Medicine Key Project(No.14401970400)National Research Projects of the State Administration of Traditional Chinese Medicine(No.201407001-2)Traditional Chinese Medicine Research Foundation(No.2012L032A)Special Project of Scientific Research Base by State Administration of Traditional Chinese Medicine(No.JDZX2012118),China
文摘Objective：To summarize and critically assess the efficacy of Eastern and Western manipulative therapies for the treatment of neck pain in adults. Methods：A search of Pub Med/MEDLINE, the Cochrane Central Register of Controlled Trials, Clinical Trials.gov, EMBASE, etc. from their inception date to January 2014 with Chinese, Japanese, and Korean databases. Two reviewers independently selected randomized controlled trials（RCTs） with negative control or blank control, extracted data and assessed methodological quality. Meta-analysis and levels of evidence were performed by Revman5.1 and Grades of Recommendations Assessment, Development and Evaluation（GRADE） approach. Results：Nineteen clinical trials with adequate randomization were included in this review, 11 of them had a low risk of bias. The primary outcome for shortterm pain had no significant differences, however, the secondary outcome, only the Numerical Pain Rating Scale（NPRS） score of intermediate-term [n=916, pooled mean differences（MD） =–0.29, P=0.02], the Neck Disability Index（NDI） score of short-term（n=1,145, pooled MD=–2.10, P〈0.01）, and intermediate-term（n=987, pooled MD=–1.45, P=0.01） were significantly reduced with moderate quality evidence. However, it supported the minimally clinically important difference（MCID） of the Visual Analogue Scale and NPRS pain score to be 13 mm, while NDI was 3.5 points. The meta-analysis only suggested a trend in favor of manipulative therapy rather than clinical significance. Conclusions：The results do not support the existing evidences for the clinical value of Eastern or Western manipulative therapy for neck pain of short-term follow-up according to MCIDs. The limitations of our review related to blinding, allocation concealment and small sample size.
基金National Natural Science Foundation of China(Nos.81860472 and 81560435)Natural Science Foundation of Jiangxi Province(No.20192ACBL21041)
文摘To the Editor:Osteosarcoma(OS),a disease seriously endangering the health of young people,is the eighth most common primary malignant bone tumor affecting children and adolescents.Typically occurring in the metaphysis of long tubular bone,OS develops from mesenchymal cells and accounts for 20%of primary bone tumors.About 70%to 80%of patients are 8 to 9 years.
基金ThisprojectwassupportedbytheNationalNaturalScienceFoundationofChina (No .30 330 70 0andNo .30 171170 )Shanghai"FutureStar"Fund (No .0 1QB14 0 39)andtheCooperativeItemofHongkongUniversityandShanghaiUniversityofTCM (No.4 72 0 0 )
文摘Objective: To analyze the gene expression profile of degenerated cervical intervertebral disc of Sprague Dawley rats on a large scale.Methods: Degenerated models of Sprague Dawley rats of 9 months old (degeneration group, n=9) and normal Sprague Dawley rats of 3 months old (control group, n=9) were prepared, respectively. mRNA was obtained from the cervical intervertebral disc of rats in both groups, respectively, and then labelled by Cy5 and Cy3 fluorescence respectively after reverse transcription to obtain intervertebral disc cDNA probes. cDNA probes were hybridized with BiostarR-40s gene expression profile chips and scanned by laser scanner. The results were treated with portrait analysis, standardization management, and ratio analysis with softwares.Results: Compared with the rats in the control group, (9.6)% (381 pieces in total) gene expression changed obviously in the rats in the degeneration group, among which, the gene expression quantities of 171 pieces increased significantly (r=the ratio of the degeneration group to the control group >(2.0)), 52 pieces of which had certain function. While the gene expression quantities of 211 pieces decreased significantly (r<(0.5)), 41 pieces of which had certain function.Conclusions: Gene chip technology can be used to analyze the gene expression profile of degenerated intervertebral disc of rats in parallel, in quantity and on a large scale, which helps to testify the representative genes and protein expression, and plays an important role in clarifying the pathogenesis of degenerated intervertebral disc.
基金Supported by the National Nature Science Foundation of China(Nos.81674006,81603343,and 81330085)the Program for Innovative Research Team of Ministry of Science and Technology of China(No.2015RA4002)
文摘Objective: To summarize and critically assess the inhibitory effects of Chinese herbal medicine(CHM) on tumor volume and tumor weight for the treatment of osteosarcoma(OS) in mouse models. Methods:PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database(CNKI), Wanfang Database, VIP Database, and Chinese BioMedical(CBM) were searched since their inception dates to March10, 2016. Two reviewers independently selected the controlled studies estimating effects of CHM on mouse OS by administration in vivo. A pair-wise meta-analysis was performed. Twenty-five studies with adequate randomization were included in the systematic review. Results: CHM may signi?cantly inhibit OS growth in mice, as assessed using the tumor weight [20 studies, n=443; 290 for CHM and 153 for the control; pooled mean difference(MD)=–2.90; 95% confidence interval(CI): –3.50 to –2.31; P<0.01], tumor volume(16 studies, n=382; 257 for CHM and 125 for the control; pooled MD =–2.57; 95% CI: –3.33 to –1.80; P<0.01) and tumor growth inhibition rate. Conclusion: CHM could significantly inhibit the growth of OS in mouse models,which might be supportive for the design of preclinical and clinical trials in future.
基金supported by National Key R&D Program of China(2018YFC1704300)National Natural Science Foundation of China(81730107,81973883)+6 种基金Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)Shanghai Scientific Research Project(17401971100)Shanghai TCM Medical Center of Chronic Disease(2017ZZ01010)Three Years Action to Accelerate the Development of Traditional Chinese Medicine Plan(ZY(2018-2020)-CCCX-3003)the Program for Innovative Research Team of Ministry of Education of China(IRT1270)the Program for Innovative Research Team of Ministry of Science and Technology of China(2015RA4002)Sanming Project of Medicine in Shenzhen(SZSM201808072).
文摘The systematicness of phenomics and Traditional Chinese Medicine(TCM)enable these two disciplines to interlink with each other.This article discussed the similarity in theory and application between TCM and phenomics and illustrates their respective advantages in diagnosis and treatment of diseases,forming a new discipline eventually.Chinese medicine phe-nomics(Chinmedphenomics)is built on classic TCM,combined with phenomics technology,and the development of which needs the mega cohort with TCM syndrome and the characteristics of precision medicine as well as multi-disciplinary coop-eration,which is personalized,precise and promising,providing unique scientific insights into understanding human health.
