Melatonin-loaded gelatin methacryloyl microspheres delay nucleus pulposus degeneration / 中国组织工程研究

BACKGROUND:Nucleus pulposus degeneration is an important pathological link of intervertebral disc degeneration.Melatonin has a protective effect on cells through anti-inflammatory and antioxidant pathways,but the effect of melatonin on the nucleus pulposus has been less studied.At present,the emergence of various biological scaffolders provides a new idea for the study of drug-material combinations.OBJECTIVE:To explore whether melatonin can improve the metabolic state of the nucleus pulposus by reducing oxidative stress damage as well as the effect of gelatin methacryloyl(GelMA)microspheres loaded with melatonin on intervertebral disc degeneration in vivo.METHODS:In vitro,melatonin was combined with GelMA solution,and GelMA hydrogel was prepared into microspheres by microfluidic technology to co-culture with nucleus pulposus cells.The cell proliferation activity was detected by cell counting kit-8 assay,the surface morphology of the microspheres was observed under scanning electron microscopy,and the rate of drug release was detected by ultraviolet spectrophotometer.Then,interleukin-1β was used to induce degeneration of the nucleus pulposus.After treatment,the expression levels of aggrecan,type Ⅱ collagen α1,matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMTS5)in the nucleus pulposus were detected by qRT-PCR.In vivo,nucleus pulposus degeneration was induced by puncture.Subsequently,GelMA and GelMA@MT microspheres were injected.After 6 weeks,the specimens were taken for tissue staining,and the changes in tissue morphology were observed under the microscope for histological analysis and scoring.RESULTS AND CONCLUSION:(1)When the GelMA and GelMA@MT microspheres were observed under electron scanning microscope,melatonin binding did not change the morphology and external appearance of the microspheres.Drug release experiments showed that the drug release reached about 80%after 40 days.(2)Cell counting kit-8 assay results showed that both GelMA and GelMA@MT microspheres had no obvious cytotoxicity and promoted the proliferation of nucleus pulposus cells.(3)qRT-PCR results revealed that GelMA@MT microspheres increased the expression of aggrecan and type Ⅰ collagen α1 in the interleukin 1β environment by 42.1%and 27.1%,respectively,and decreased the expression of matrix metalloproteinase 13 and ADAMTS5 by 70.7%and 109.3%,respectively.(4)The level of reactive oxygen species was significantly lower in the interleukin 1β+GelMA@MT group than in the interleukin 1β and interleukin 1β+GelMA groups.(5)Histological staining of the sections showed that melatonin-loaded GelMA microspheres significantly delayed disc degeneration in vivo.(6)These findings indicate that GelMA@MT microspheres made by combining melatonin with GelMA hydrogel have good cytocompatibility in vitro and significantly delay nucleus pulposus degeneration in vitro and in vivo.

In vitro evaluation of sustained release Kartogenin by gelatin methacryloyl microspheres for repairing nucleus pulposus degeneration / 中国组织工程研究

BACKGROUND:The imbalance of matrix synthesis and degradation is the main cause of nucleus pulposus degeneration.Small molecule drug Kartogenin(KGN)can restore the balance of matrix synthesis and degradation.Sustained release of KGN using an appropriate drug delivery system is essential for the long-term and effective treatment of KGN.OBJECTIVE:To prepare the injectable hydrogel microspheres by encapsulating KGN with gelatin methacryloyl(GelMA)by microfluidic technology and to investigate the biocompatibility and biological function of nucleus pulposus cells.METHODS:β-Cyclodextrins(β-CD)and KGN were mixed firstly and then mixed with 10%GelMA at a volume of 1:9.Injectable hydrogel microspheres GelMA@β-CD@KGN were prepared by microfluidic technology.The micromorphology of the microspheres was characterized using a scanning electron microscope.The drug release of hydrogel microspheres immersed in PBS within one month was measured.Nucleus pulposus cells were isolated from SD rats and passage 1 cells were cultured in three groups.In the control group,nucleus pulposus cells were cultured separately.In the other two groups,GelMA@β-CD microspheres and GelMA@β-CD@KGN microspheres were co-cultured with nucleus pulposus cells.Cell proliferation was detected by CCK-8 assay and cell survival was detected by live/dead cell staining.Cells were cultured by two complete media with and without interleukin-1β with two kinds of microspheres.mRNA expressions of matrix synthesis and decomposing proteins in nucleus pulposus cells were detected by RT-PCR.RESULTS AND CONCLUSION:(1)Under the scanning electron microscope,the GelMA@β-CD@KGN microspheres after lyophilization were regularly spherical,highly dispersed,uniform in size and full in shape.GelMA@β-CD@KGN microspheres sustained drug release in vitro,reaching 62%of the total drug release at 30 days.(2)Live/dead cell staining showed that GelMA@β-CD@KGN could maintain the activity of nucleus pulposus cells.CCK-8 assay showed that GelMA@β-CD@KGN could promote the proliferation of nucleus pulposus cells.(3)In the complete media with and without interleukin-1β,mRNA expression of aggrecan and type Ⅱ collagen was higher in the GelMA@β-CD@KGN microsphere group than that in the GelMA@β-CD microsphere group(P<0.05,P<0.01);mRNA expression of matrix metalloproteinase 13 and platelet reactive protein disintegrin metallopeptidase 5 was lower than that in the GelMA@β-CD microsphere group(P<0.01).(4)These findings indicate that GelMA@β-CD@KGN microspheres have good biocompatibility and sustained drug release ability.As a drug delivery system,it is a kind of biomaterial with broad application prospects.

Melatonin alleviates CoCrMo particle-induced osteolysis by inhibiting NLRP3 inflammasome activation / 中国组织工程研究

BACKGROUND:Periprosthetic osteolysis is the most common long-term complication of total joint arthroplasty.Many studies suggest that the inflammasome may play an important role during the osteolysis.Melatonin is a rhythm-regulated hormone secreted by the pineal gland with many functions including anti-inflammatory,anti-oxidation,and antitumor,but its effects on osteolysis and inflammasome have yet to be explored. OBJECTIVE:To explore the effect of melatonin on the osteolysis induced by wear particles and the role of melatonin on the activation of NLRP3 inflammasome. METHODS:(1)In vivo test:Fifteen C57BL/6 mice were randomly divided into sham operation group,osteolysis group and melatonin group by random number table method,with 5 mice in each group.The osteolysis model of the osteolysis group and the melatonin group was established by injecting cobalt-chromium-molybdenum(CoCrMo)particles into the sagittal suture of the skull.After injection,the melatonin group was intraperitoneally injected with 50 mg/(kg·d)of melatonin for 14 consecutive days.After drug intervention,the mouse calvarium was collected for micro-CT analysis to observe the micro-structural changes around the sagittal suture.(2)In vitro test:Mouse bone marrow-derived macrophages and THP-1 cells(which had been induced to differentiate into macrophages)were taken and divided into seven groups:normal group,lipopolysaccharide group,lipopolysaccharide+CoCrMo group and melatonin 0.5,1,1.5,2 mmol/L groups(lipopolysaccharide and CoCrMo were added to the melatonin intervention groups).After the intervention for 6 hours,the expression of related proteins(NLRP3,Caspase-1,interleukin-1β,and gasdermin D,gasdermin D-N terminal)in the inflammasome of cell lysate or cell culture supernatant was detected by western blot assay.Cytotoxicity and cell death were observed through lactate dehydrogenase release and live-dead fluorescence staining. RESULTS AND CONCLUSION:(1)In vivo test:Micro-CT scanning 3D reconstruction images showed that the bone mass around the sagittal suture of the skull of mice in the osteolysis group was significantly reduced,and the bone tissue structure was severely damaged.Compared with the osteolysis group,the bone mass around the sagittal suture of the skull in the melatonin group was significantly increased,and the destruction of tissue structure was reduced.(2)In vitro test:For mouse bone marrow-derived macrophages,lipopolysaccharide significantly up-regulated NLRP3 protein expression in cell lysate,and melatonin intervention could reduce NLRP3 protein expression in a dose-dependent manner.CoCrMo particles significantly up-regulated the protein expressions of the gasdermin D-N terminal in cell lysate and Caspase-1 and interleukin-1β in the supernatant of cell culture,while melatonin intervention could reduce the expression of these proteins in a dose-dependent manner.For THP-1 cells,the protein expressions of Caspase-1 and interleukin-1β in the supernatant of cell culture were significantly up-regulated by CoCrMo particles,and the expression of these proteins was decreased dose-dependent by melatonin intervention.Lactate dehydrogenase release and live-dead fluorescence staining showed that CoCrMo particles significantly increased the release of lactate dehydrogenase and cell death in the supernatant of mouse bone marrow-derived macrophage culture,and melatonin intervention could reduce the release of lactate dehydrogenase and cell death.(3)The results show that melatonin can inhibit particle-induced inflammasome activation and pyroptosis to suppress periprosthetic osteolysis.

Application of strontium polyphosphate with both radiopaque and osteogenic functions in calcium phosphate cement / 中国组织工程研究

BACKGROUND:Our previous studies found that adding barium sulfate could improve the mechanical and radiopaque properties of calcium phosphate cement.However,with the degradation of calcium phosphate,the remaining radiopaque agent is difficult to degrade,and the space-occupying and osteoclast effects at the implantation site affect the bone repair process.Therefore,it is necessary to develop a new biodegradable radiopaque material. OBJECTIVE:To discuss the radiopaque ability of bioactive degradable material strontium polyphosphate(SrPP)and its impact on the physicochemical properties and osteogenic effect of calcium phosphate cement. METHODS:(1)Calcium phosphate cement(CPC),starch modified calcium phosphate cement(CPS)and starch modified calcium phosphate cement(20%SrPP-CPN)containing SrPP(20%mass fraction of bone cement powder)were prepared respectively,and the physicochemical properties of the three groups of bone cements were characterized.(2)The three groups of bone cement extracts were co-cultured with rat bone marrow mesenchymal stem cells,respectively,to detect cell proliferation,energy metabolism,and osteogenic differentiation.(3)Bone defects with a diameter of 5 mm were made on each side of the top of the skull of 24 SD rats,and they were randomly divided into control group(without any intervention),CPC group,CPS group,and 20%SrPP-CPN group for intervention,with 6 rats in each group.Relevant tests were performed after 4 and 12 weeks of intervention. RESULTS AND CONCLUSION:(1)Compared with the other two groups of bone cement,20%SrPP-CPN had enhanced radiopaque ability,increased compressive strength and degradation rate,and prolonged curing time,and 20%SrPP-CPN could release Sr2+ stably during degradation.(2)CCK-8 assay showed that 20%SrPP-CPN did not affect the proliferation of bone marrow mesenchymal stem cells.Cell starvation test(serum-free culture)showed that 20%SrPP-CPN could promote the proliferation of bone marrow mesenchymal stem cells compared with the other two groups of bone cement.Compared with the other two groups of bone cements,20%SrPP-CPN increased adenosine triphosphate concentration in bone marrow mesenchymal stem cells.Alkaline phosphatase and alizarin red staining showed that 20%SrPP-CPN could promote osteogenic differentiation of bone marrow mesenchymal stem cells compared with the other two groups of bone cement.(3)In the rat skull defect experiment,Micro-CT scanning and histological observation(hematoxylin-eosin and Masson stainings)showed that bone cement in 20%SrPP-CPN group was significantly degraded compared with that in CPC and CPS groups,and a large number of new bone tissues were dispersed in degraded bone cement.Immunohistochemical staining showed that Runx2 protein expression was increased in 20%SrPP-CPN group compared with CPC group and CPS group(P＜0.01).(4)These results show that 20%SrPP-CPN has good radiopaque ability and osteogenic properties.

Treatment of cement dislodgement after vertebral augmentation / 中华创伤骨科杂志

Objective:To analyze the clinical efficacy of treatment of cement dislodgement after vertebral augmentation for osteoporotic vertebral fractures.Methods:A retrospective study was conducted to analyze the data of 13 patients who had been treated at Department of Orthopaedics, The First Affiliated Hospital of Soochow University for cement dislodgement after vertebral augmentation for osteoporotic vertebral fractures from July 2013 to July 2022. There were 4 males and 9 females, with an average age of (76.5±8.6) years and a T value of bone mineral density of -3.3±0.6. By the CT and MRI features of cement dislodgement, their conditions fell in 4 types: cement loosening in situ (4 cases), anterior cement moving (6 cases), anterior cement moving with posterior bone mass moving (2 cases), and posterior cement moving (1 case). They were treated by percutaneous vertebroplasty (3 cases), pedicle screw fixation combined with bone graft fusion and decompression (7 cases), and conservative therapy (3 cases). The curative effects for surgical patients were evaluated by comparing their visual analogue scale (VAS), Oswestry dysfunction index (ODI) and cobb angle of kyphosis at preoperation, 1 week and 1 month postoperation, and the last follow-up, and Frankel grading for nerve injury as well. The curative effects for patients undergoing conservative treatment were evaluated by observing their symptoms.Results:This cohort was followed up for 7 (5, 12) months after treatment. The VAS scores [5.0 (4.0, 5.0) points, 3.0 (2.0, 3.0) points, and 3.0 (2.0, 3.0) points] in the 10 surgical patients at 1 week and 1 month postoperation and the last follow-up were significantly improved compared with the preoperative value [8.5 (8.0, 9.0) points] ( P<0.05); the VAS scores at 1 month postoperation and the last follow-up were also significantly improved compared with that at 1 week postoperation ( P < 0.05), but there was no significant difference between the last follow-up and 1 month postoperation ( P > 0.05). The ODIs (50.6%±4.2%, 37.8%±4.5%, and 29.3%±5.6%) in the 10 surgical patients at 1 week and 1 month postoperation and the last follow-up were significantly improved compared with the preoperative value (93.2%±3.6%), showing significant differences in pairwise comparisons ( P<0.05). The cobb angles [10.0 (9.0, 11.0)°, 9.0 (9.0, 11.0)°, and 10.0 (9.0, 12.0)°] in the 10 surgical patients at 1 week and 1 month postoperation and the last follow-up were significantly improved compared with the preoperative value [12.5 (11.0, 14.0)°] ( P<0.05) , but there was no statistically significant difference between the time points after operation ( P>0.05). The Frankel grading was significantly improved in the 6 patients with nerve injury after operation. Of the 3 patients undergoing conservative treatment, the symptoms were cured in one, showed no change during follow-up in one, and aggravated in one. Conclusion:Surgical treatment can significantly relieve pain, improve spinal dysfunction and repair nerve injury in patients with bone cement dislodgement after vertebral augmentation.

Risk factors for residual pain after percutaneous kyphoplasty for osteoporotic vertebral fractures / 中华创伤骨科杂志

Objective:To analyze the risk factors for residual pain after percutaneous kyphoplasty (PKP) for osteoporotic vertebral fractures (OVF).Methods:Retrospectively analyzed were the patients with OVC who had been treated at Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University by single level PKP from January 2020 to December 2021. They were 40 men and 181 women, with an age of (69.6±8.2) years. By the pain score of visual analogue scale (VAS) on the postoperative day 3, they were assigned into 2 groups: a residual pain group (VAS≥4) and a control group (VAS<4). The general demographics, radiographic and surgical related data of the 2 groups were analyzed by single factor analysis, including their gender, age, bone mineral density, body mass index, glucocorticoid usage, follow-up time, duration of symptoms, fracture location, severity of fracture compression, intravertebral cleft, middle column involvement, thoracolumbar fascia injury, anesthesia method, puncture method, volume of bone cement injected, cement-endplates contact, pattern of cement distribution, cement leakage, vertebral height restoration, preoperative cobb angle and correction of cobb angle. The P<0.1 factors screened were further analyzed by the multivariate logistic regression to determine the final variables. Results:In the present study, 19 patients were assigned into the residual pain group and 202 patients the control group. The univariate analysis showed that body mass index ( P=0.059), intravertebral cleft ( P=0.049) and thoracolumbar fascia injury ( P< 0.001) increased the risk for residual pain. The multivariate logistic regression analysis showed that thora-columbar fascia injury was an independent risk factor for residual pain ( OR=6.127, 95% CI: 2.240 to 16.755, P<0.001). Conclusion:Thoracolumbar fascia injury is an independent risk factor for residual pain after PKP for OVF.

Nimbolide targeting SIRT1 mitigates intervertebral disc degeneration by reprogramming cholesterol metabolism and inhibiting inflammatory signaling

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.

Ginger-indirect moxibustion plus acupuncture versus acupuncture alone for chronic fatigue syndrome: a randomized controlled trial.

OBJECTIVE: To assess the efficacy and safety of ginger-indirect moxibustion for chronic fatigue syndrome (CFS). METHODS: In this central randomized, controlled trial, 290 CFS participants were recruited and randomly allocated to group A (ginger-indirect moxibustion plus acupuncture) or group B (acupuncture alone). The study consisted of a treatment period of 8 weeks with a total of 24 treatments (3 sessions per week, every other day), and a follow-up period of 12 weeks. The outcome was measured by Fatigue Severity Scale (FSS), Psychological Health Report (SPHERE), the Self-rating depression scale (SDS) and the Hamilton anxiety scale (HAMA) at baseline, 2, 4, 6, 8, 12 and 20 weeks. RESULTS: With the treatment undergoing, the changes of FSS, SPHERE, SDS and HAMA scores in both groups increased gradually, and the effect maintained at the 12th week. Between groups, significantly higher score changes were seen in group A in FSS after 4 weeks treatment (11.94 9.12, 95%: 0.94, 4.7) and in SPHERE after 2 weeks treatment (3.7 2.27, 95%: 0.56, 2.31). But for SDS and HAMA, the improvement did not differ significantly between groups. No severe adverse events were reported. CONCLUSION: Ginger-indirect moxibustion is a safe and effective intervention to relieve fatigue and accompanying physical symptoms of CFS.

Evaluating the Reproducibility of the Walking Test for Intermittent Claudication Associated with Lumbar Spinal Stenosis.

STUDY DESIGN: This is a multicenter, prospective study. PURPOSE: This study aimed to evaluate the reproducibility of the walking test for patients with lumbar spinal stenosis (LSS). OVERVIEW OF LITERATURE: Walking test is one of the useful procedures to investigate cauda equina syndrome with lumbar spinal stenosis. One the other hands, there were few studies to investigate the reproducibility of this test. METHODS: In this study, we prospectively examined 70 LSS patients with intermittent claudication symptoms at a multicenter outpatient clinic. A walking test was administered at baseline and week 4 to assess patients' walking distance and lower limb pain and numbness. Immediately after the walking test, patients were asked to use the Visual Analog Scale (VAS) to rate their pain and numbness in the front, back, outside, inside, and hip of the lower legs. The reproducibility of the walking test was evaluated using Cohen's κ analysis and intraclass correlation coefficients (ICCs). Meanwhile, the Swiss Spinal Stenosis (SSS) Questionnaire was used to evaluate the severity of the stenosis. RESULTS: The walking distance ICC at baseline and at week 4 remained unchanged at 0.7, with acceptable interobserver reliabilities for lower limb pain and numbness in both legs. The average VAS score for lower leg pain was 23.2±25.2 mm at baseline and 27.4±28.8 mm at week 4, while the corresponding average VAS score for numbness was 23.4±26.7 mm at baseline and 24.8±25.2 mm at week 4. The ICC score was 0.7 for leg pain and 0.7 for numbness. The mean SSS was 30.2±5.5 at baseline and 29.2±5.2 at week 4, and there was no significant difference in the severity. CONCLUSIONS: The walking test for LSS has acceptable reproducibility.

Status of minimally invasive treatment for adjacent segment disease after lumbar interbody fusion / 中华骨科杂志

Adjacent segment degeneration (ASDeg) is a common complication occurring in patients after lumbar fusion, mainly manifested as adjacent disc herniation, adjacent vertebral fracture or spondylolisthesis, adjacent segment scoliosis, adjacent segment spinal canal stenosis or facet joint degeneration, etc. When patients with imaging manifestations of ASDeg present with clinical symptoms such as lumbosacral pain, root lower limb pain or intermittent claudication, it is called adjacent segment disease (ASDis), and reoperation is often required at this time. At present, open surgery has been widely used in the treatment of symptomatic ASDis, including fusion via posterior approach and transforaminal approach, etc. The traditional surgery is effective, but it always has many disadvantages, such as large surgical trauma, large intraoperative blood loss, long operation time and hospital stay, and slow postoperative recovery. Therefore, surgeons are actively trying to apply various minimally invasive procedures to the treatment for symptomatic ASDis. Anterior lumbar interbody fusion (ALIF) has better recovery effect on intervertebral space height and lumbar lordosis, but it also has higher risk of vascular, urinary system and abdominal organ injury. Minimally invasive transforaminallumbar interbody fusion (MIS-TLIF) has a significant effect on the protection of muscles (such as multifidus muscle) and ligaments. However, compared with open surgery, MIS-TLIF has a limited effect on the correction of coronal and sagittal malformations, and has a higher incidence of superior facet joint violation. lateral lumbar interbody fusion (LLIF) has significant correction effect on coronal and sagittal malformations, complete treatment of intervertebral space, high intervertebral fusion rate, and good intervertebral space height recovery. However, due to the influence of the iliac crest, the surgical segment of LLIF is limited, and there is a risk of injury to the lumbar plexus and iliac vessels at the lower lumbar spine. Extreme lateral lumbar interbody fusion (XLIF) has a low risk of iliac vascular injury, little impact on the original internal fixation, and good interbody fusion effect. However, XLIF is not suitable for patients with a history of retroperitoneal surgery, retroperitoneal abscess, or vascular anatomical abnormalities, and neurological monitoring is often needed during surgery. Compared with open surgery, oblique lumbar interbody fusion (OLIF) has the advantages of less surgical trauma and low risk of common complications (such as dural injury). However, due to the need to pull the sympathetic nerve during operation, OLIF may lead to postoperative limb cold and heat disorders, thus affecting the judgment of surgical decompression effect. Percutaneous endoscopic lumbar discectomy (PELD) can fully decompress the nerve and dural sac while causing less damage to the posterior spinal structure. However, it is not suitable for patients with ASDis complicated with severe spinal stenosis, lumbar spondylolisthesis or cauda equina syndrome. At the same time, PELD has a steeper learning curve than other procedures. Percutaneous endoscopic lumbar interbody fusion (PELIF) also has the disadvantages of steep learning curve and easy to damage outlet nerve, but it has the advantages of less blood loss, shorter hospital stay, faster recovery, and fewer complications (such as deep vein thrombosis and pulmonary embolism) compared with open surgery. This paper reviews the advantages and disadvantages of different minimally invasive procedures in the treatment of symptomatic ASDis and the indications of different minimally invasive procedures through literature retrieval, in order to provide reference for the future minimally invasive methods in the treatment of symptomatic ASDis.

Clinical efficacy of immunotherapy combined with targeted therapy for postoperative recur-rent hepatocellular carcinoma / 中华消化外科杂志

Systemic therapy is the preferred treatment option for advanced primary hepatic carcinoma, and the results of clinical study IMbrave150 suggesting the superiority of atezolizumab combined with bevacizumab for the treatment of hepatocellular carcinoma. The authors introduce the clinical experience of one patient with postoperative recurrent primary hepatic carcinoma who was treated with atezolizumab plus bevacizumab followed by radiotherapy. The results reveal that the efficacy as stable disease during immunotherapy combination of targeted therapy and partial response after radiotherapy, and the patient tolerating well with a high quality of life.

Risk factors for bone cement leakage and recompression of injured vertebrae after percutaneous kyphoplasty for osteoporotic vertebral compression fracture / 中华创伤杂志

Objective:To investigate the risk factors of bone cement leakage and recompression of injured vertebrae after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF).Methods:A case-control study was performed to analyze the clinical data of 297 patients with single-segment OVCF who underwent PKP in First Affiliated Hospital of Soochow University from January 2017 to January 2021, including 67 males and 230 females; aged 60-92 years [(69.5±8.2)years]. According to the occurrence of bone cement leakage, the patients were divided into leakage group ( n=36) and no leakage group ( n=261). According to the occurrence of recompression of injured vertebrae, the patients were divided into recollapse group ( n=40) and no recollapse group ( n=257). The gender, age, fracture segment, type of fracture, fracture severity, cortical disruption, intravertebral cleft, preoperative and postoperative local kyphosis angle, correction value of local kyphosis angle, bone cement injection volume, bone cement distribution, and postoperative anti-osteoporosis treatment were recorded. Univariate analysis was used to analyze the correlation of those factors with bone cement leakage and recompression of injured vertebrae after PKP, followed by multivariate Logistic regression analysis to identify the independent risk factors. Results:Univariate analysis showed that fracture severity, cortical disruption and bone cement injection volume were related to bone cement leakage ( P<0.05 or 0.01). Gender, age, fracture segment, type of fracture, intravertebral cleft, preoperative and postoperative local kyphosis angle, correction value of local kyphosis angle, bone cement distribution, and postoperative anti-osteoporosis treatment were not related to bone cement leakage (all P>0.05). Univariate analysis showed that intravertebral cleft, bone cement distribution, and postoperative anti-osteoporosis treatment were associated with recompression of injured vertebrae (all P<0.01). Gender, age, fracture segment, type of fracture, fracture severity, cortical disruption, preoperative and postoperative local kyphosis angle, correction value of local kyphosis angle, and bone cement injection volume were not related to recompression of injured vertebrae (all P>0.05). Multivariate Logistic regression analysis showed that severe fracture ( OR=4.23, 95% CI 1.52-11.81, P<0.01), cortical disruption ( OR=3.29,95% CI 1.52-7.13, P<0.01), and bone cement injection volume >8 ml ( OR=2.31,95% CI 1.09-4.92, P<0.05) were significantly related to bone cement leakage. Multivariate Logistic regression analysis showed that intravertebral cleft ( OR=2.10, 95% CI 1.03-4.30, P<0.05), solid type of bone cement distribution ( OR=2.56, 95% CI 1.25-5.27, P<0.05) and no anti-osteoporosis treatment after operation ( OR=3.06, 95% CI 1.46-6.40, P<0.01) were significantly related to recompression of injured vertebrae. Conclusions:For OVCF patients, severe fracture, cortical disruption, and bone cement injection volume>8 ml are independent risk factors for bone cement leakage after PKP. Intravertebral cleft, solid type of bone cement distribution, and no anti-osteoporosis treatment after operation are independent risk factors for recompression of injured vertebrae after PKP.

TEG evaluation and blood transfusion prediction model for patients with upper gastrointestinal bleeding / 中国输血杂志

【Objective】 To establish a blood transfusion outcome prediction model for comprehensivel evaluation of coagulation function of patients with upper gastrointestinal bleeding by thrombelastogram (TEG) and blood coagulation indicators. 【Methods】 The data of 101 patients with upper gastrointestinal hemorrhage, admitted to the Department of Gastroenterology of Zhejiang Provincial People′s Hospital and its Chun′an Branch from June 2018 to June 2021, were collected through Tongshuo blood transfusion management system and His system. Those patients were divided into blood transfusion group (n=56) and non-transfusion group (n=45), and into cirrhosis group (n=74) and non-cirrhosis group (n=27), and 40 patients, with non-upper gastrointestinal bleeding, were enrolled as the control. The results of TEG indicators (R, K, α, MA), coagulation function (PT, INR, APTT, TT, Fib), blood routine (Hb, Plt, WBC, NEUT%) and biochemical detection(Alb, SCr, ALT, AST, GGT) before transfusion were compared between groups and the correlation between TEG indicators and traditional coagulation parameters was analyzed. Single-factor and multi-factor analysis were used to screen blood transfusion-related factors to establish a predictive model. 【Results】 The comparisons of paremeters between transfusion and non-transfusion group were as follows, K (min), α (°), and MA (mm) was 3.86±3.12 vs 2.50±1.47, 54.00±14.08 vs 61.05±10.88, and 51.12±13.37 vs 58.26±11.08, respectively (P<0.01); PT (s) and Fib (g) was 16.36±7.45 vs 13.44±1.50 and 1.59±0.87 vs 2.35±1.09 (P<0.01); NEUT% and Hb (g/L) was 0.75 ±0.13 vs 0.66±0.15 and 68.04±14.49 vs 100.73±22.92 (P<0.01); Alb (g/L) and SCr (nmol/L) was 29.73±6.08 vs 33.73±7.19 and 99.50±53.55 vs 76.25±19.28 (P<0.01). Correlation analysis showed that APTT was positively correlated with R and K values, and negatively correlated with α and MA. Fib was negatively correlated with K values, and positively correlated with α and MA. Plt was negatively correlated with K values, and positively correlated with α and MA (P<0.01). Eight pre-transfusion indicators as K, MA, PT, Fib, NEUT%, Hb, Alb, and SCr were subjected to Logistic regression to establish a blood transfusion prediction model. The optimal ROC curve of blood transfusion threshold (blood transfusion predictive value of patients), sensitivity, specificity and AUC were 0.448, 92.9%, 88.9%, and 0.969, respectively. 【Conclusion】 The establishment of Logistic regression model by integrating detection indicators of TEG, coagulation function, blood routine and biochemistry in patients with upper gastrointestinal bleeding have showed significant correlation with blood transfusion prediction, and good clinical practicability.

Advice on Standardized Diagnosis and Treatment for Spinal Diseases during the Coronavirus Disease 2019 Pandemic

Coronavirus disease 2019 (COVID-19) outbreak started in December 2019 that caused difficulties for clinical work. Practical work experience in our spinal outpatient and emergency department during the COVID-19 pandemic is summarized in this article, with combined evidence-based medical evidence to explore a standardized process of diagnosis and treatment for spinal diseases. Outpatient reservation, continuous screening, triage, and isolation, first consultation accountability system, pandemic reporting system, and online revisit were strictly followed. We hope that our experience in prevention and control of COVID-19 can help spine surgeons globally in stopping the spread of COVID-19. Spine surgeons should collaborate with infection control specialists to avoid cross-infection in hospitals and optimize treatment.

Small dose of low molecular weight heparin improves the prognosis of elderly patients with severe pneumonia: a Meta-analysis of 1 173 patients / 中华危重病急救医学

Objective:To explore the effect of small dose of low molecular weight heparin on the prognosis of elderly patients with severe pneumonia using systematic evaluation method.Methods:Databases including Wanfang data, VIP, CNKI, SinoMed, PubMed, Embase and Cochrane Library were searched for randomized controlled trial (RCT) studies about the comparison of conventional therapy and low molecular weight heparin on prognosis of elderly patients with severe pneumonia from the time of database establishment to August 2019. The patients in conventional treatment group were treated by improving ventilation, anti-infection, eliminating phlegm, relieving asthma and maintaining homeostasis while those in low molecular weight heparin group were subcutaneously injected with low molecular weight heparin of 4 000 U, once a day for 7 days. The patients' main outcomes included the oxygenation index (PaO 2/FiO 2) after 7 days of treatment, duration of mechanical ventilation, mortality in hospital, and secondary outcomes included acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score and coagulation function after 7 days of treatment, the length of intensive care unit (ICU) stay, and incidence of bleeding. Data extraction and quality evaluation were conducted. The Meta-analysis of included studies that met the quality standards was performed using RevMan 5.3 software. Funnel diagram analysis was used to analyze the parameters with no less than 10 studies enrolled. Results:A total of 14 RCT studies were enrolled involving 1 173 elderly patients with severe pneumonia, among whom 590 received low molecular weight heparin while the other 583 received conventional therapy. All the included studies were well designed and of high quality. The results of Meta-analysis showed that compared with conventional therapy, small dose of low molecular weight heparin significantly elevated PaO 2/FiO 2 after 7 days of treatment [mean difference ( MD) = 19.25, 95% confidence interval (95% CI) was 16.88 to 21.61, P < 0.000 01], shortened the duration of mechanical ventilation ( MD = -48.88, 95% CI was -67.42 to -30.33, P < 0.000 01), and decreased mortality in hospital [odds ratio ( OR) = 0.40, 95% CI was 0.22 to 0.73, P = 0.003] and APACHEⅡ score after 7 days of treatment ( MD = -3.38, 95% CI was -3.94 to -2.83, P < 0.000 01), and shortened the length of ICU stay ( MD = -4.51, 95% CI was -5.75 to -3.27, P < 0.000 01). There was no significant difference in the changes of coagulation parameters after 7 days of treatment or the incidence of bleeding between low molecular weight heparin group and conventional therapy group [7-day thrombin time (TT): MD = 0.57, 95% CI was -0.15 to 1.28, P = 0.12; 7-day prothrombin time (PT): MD = 0.32, 95% CI was -0.35 to 0.98, P = 0.35; 7-day fibrinogen (FIB): MD = -0.17, 95% CI was -0.45 to 0.10, P = 0.22; incidence of bleeding: OR = 0.86, 95% CI was 0.36 to 2.07, P = 0.74]. The funnel diagram showed that there was publication bias of included 10 studies about APACHEⅡ score after 7 days of treatment. Conclusion:Small dose of low molecular weight heparin can improve the prognosis of elderly patients with severe pneumonia and it has no obvious side-effect on coagulation function.

Clinical guideline for surgical treatment of symptomatic chronic osteoporotic vertebral fractures / 中华创伤杂志

According to the pathological characteristics of symptomatic chronic thoracic and lumbar osteoporotic vertebral fracture (SCOVF), the different clinical treatment methods are selected, including vertebral augmentation, anterior-posterior fixation and fusion, posterior decompression fixation and fusion, and posterior correction osteotomy. However, there is still a lack of a unified understanding on how to choose appropriate treatment method for SCOVF. In order to reflect the new treatment concept and the evidence-based medicine progress of SCOVF in a timely manner and standardize its treatment, the clinical guideline for surgical treatment of SCOVF is formulated in compliance with the principle of scientificity, practicability and advancement and based on the level of evidence-based medicine.

Inhibitory effect of pills against diethylnitrosamine-induced hepatocarcinogenesis in rats / 南方医科大学学报

OBJECTIVE@#To study the inhibitory effect of pills (BJJ) agaisnt diethylnitrosamine (DEN)-induced hepatocarcinogenesis and explore the relation between this effect and the inflammasome signaling pathway.@*METHODS@#Sixty-five male SD rats were randomly divided into control group, DEN model group, and 3 BJJ treatment groups at low, medium and high dose (with daily dose of 0.55, 1.1 and 2.2 g/kg, respectively, for 12 consecutive weeks starting from the 5th week after modeling). The pathological changes of the liver tissue were observed with HE and Masson staining, and serum levels of alanine transaminase (ALT), glutamic oxaloacetic transaminase (AST), alkaline phosphatase (ALP) and total bilirubin (TBIL) of the rats were detected using ELISA. Oxidation stress in the liver tissue was assessed with ELISA, and Western blotting and ELISA were used to detect the molecular expressions of inflammasome-related pathway.@*RESULTS@#BJJ significantly inhibited tumor growth in the liver of the rats. HE and Masson staining showed that BJJ treatment obviously ameliorated liver fibrosis and reduced cancer cell and inflammatory cell infiltration in the liver. BJJ significantly reduced elevations of serum ALT, AST, ALP and TBIL levels, increased the contents of superoxide dismutase, catalase and glutathione peroxidase in the liver and suppressed malondialdehyde in Den-treated rats. BJJ also dose-dependently decreased the expressions of NLRP3, apoptosis-associated speck-like protein (ASC), caspase-1, pro-IL-1β, pro-IL-18, IL-1β and IL-18 in the liver of Den-treated rats.@*CONCLUSIONS@#BJJ treatment can dose-dependently inhibit DEN-induced hepatocarcinogenesis by enhancing antioxidant capacity and down-regulating inflammatory-related pathways in rats.

Schisantherin B Improves the Pathological Manifestations of Mice Caused by Behavior Desperation in Different Ages-Depression with Cognitive Impairment

Depression is a major mood disorder. Abnormal expression of glial glutamate transporter-1 (GLT-1) is associated with depression. Schisantherin B (STB) is one bioactive of lignans isolated from Schisandra chinensis (Turcz.) Baill which has been commonly used as a traditional herbal medicine for thousands of years. This paper was designed to investigate the effects of STB on depressive mice induced by forced swimming test (FST). Additionally, we also assessed the impairment of FST on cognitive function in mice with different ages. FST and open field test (OFT) were used for assessing depressive symptoms, and Y-maze was used for evaluating cognition processes. Our study showed that STB acting as an antidepressant, which increased GLT-1 levels by promoting PI3K/AKT/mTOR pathway. Although the damage is reversible, short-term learning and memory impairment caused by FST test is more serious in the aged mice, and STB also exerts cognition improvement ability in the meanwhile. Our findings suggested that STB might be a promising therapeutic agent of depression by regulating the GLT-1 restoration as well as activating PI3K/AKT/mTOR pathway.

Effect of surgical factors on the augmentation of cement-injectable cannulated pedicle screw fixation by a novel calcium phosphate-based nanocomposite / 医学前沿

Bone cement-augmented pedicle screw system demonstrates great efficacy in spinal disease treatments. However, the intrinsic drawbacks associated with clinically used polymethylmethacrylate (PMMA) cement demands for new bone cement formulations. On the basis of our previous studies, a novel injectable and biodegradable calcium phosphate-based nanocomposite (CPN) for the augmentation of pedicle screw fixation was systematically evaluated for its surgical feasibility and biomechanical performance by simulated and animal osteoporotic bone models, and the results were compared with those of clinical PMMA cement. ASTM-standard solid foam and open-cell foam models and decalcified sheep vertebra models were employed to evaluate the augmentation effects of CPN on bone tissue and on the cement-injected cannulated pedicle screws (CICPs) placed in osteoporotic bone. Surgical factors in CICPs application, such as injection force, tapping technique, screw diameter, and pedicle screw loosening scenarios, were studied in comparison with those in PMMA. When directly injected to the solid foam model, CPN revealed an identical augmentation effect to that of PMMA, as shown by the similar compressive strengths (0.73 ± 0.04 MPa for CPN group vs. 0.79 ± 0.02 MPa for PMMA group). The average injection force of CPN at approximately 40-50 N was higher than that of PMMA at approximately 20 N. Although both values are acceptable to surgeons, CPN revealed a more consistent injection force pattern than did PMMA. The dispersing and anti-pullout ability of CPN were not affected by the surgical factors of tapping technique and screw diameter. The axial pullout strength of CPN evaluated by the decalcified sheep vertebra model revealed a similar augmentation level as that of PMMA (1351.6 ± 324.2 N for CPN vs. 1459.7 ± 304.4 N for PMMA). The promising results of CPN clearly suggest its potential for replacing PMMA in CICPs augmentation application and the benefits of further study and development for clinical uses.