BACKGROUND:Spinal canal decompression using uniportal endoscopic surgery is a new minimally invasive surgery in the treatment of lumbar spinal stenosis.However,this technique needs a steep learning curve and high requirements for surgical equipment and instruments,which limits its clinical application.We previously use the spinal endoscopy as a monitoring endoscopy and combined with unilateral biportal endoscopy to propose a hybrid technique of spinal endoscopy to achieve coaxial endoscopic operation and hands-separate operation. OBJECTIVE:To compare the clinical outcome of hybrid technique and uniportal endoscopic surgery in treatment of lumbar spinal stenosis with bilateral lower limb pain symptoms. METHODS:Ninety patients diagnosed of lumbar spinal stenosis with bilateral symptoms were included and retrospectively analyzed at First People's Hospital,Shanghai Jiao Tong University from August 2020 to August 2022.44 cases were included in group A(hybrid technique group),while 46 cases were included in group B(uniportal endoscopic surgery).The nerve decompression was observed during the surgery.Operation time,hospital stay time,and expenses were recorded in both groups.The visual analog scale scores of lower back pain and both lower extremities pain,Oswestry disability index scores of quality of life and excellent and good rate of modified Macnab criteria were recorded and compared at preoperative,postoperative 3 days,and postoperative 3 and 6 months. RESULTS AND CONCLUSION:(1)The operation time of group A was significantly shorter than that of group B(P<0.05).(2)The lower back pain and lower extremity pain of the severe side at postoperative 3 days,and 3 and 6 months were significantly relieved in both groups(P<0.05).The visual analog scale score of lower extremity pain on the mild side was significantly decreased at postoperative 3 days,3 and 6 months than preoperative score in the group A(P<0.05).The visual analog scale score of lower extremity pain on the mild side was significantly decreased at postoperative 3 days than preoperative score in the group B(P<0.05).The visual analog scale scores of lower extremity pain on the mild side at postoperative 3 and 6 months did not show significant difference than preoperative score in the group B.The comparison between the two groups showed that there was no significant difference in the visual analog scale scores of postoperative lower back pain and lower extremity pain of the severe side(P>0.05).The visual analog scale scores of lower extremity pain on the mild side in the group A were significantly lower than those of group B at postoperative 3 and 6 months(P<0.05).(3)The Oswestry disability index scores of both groups at postoperative 3 day were significantly lower than preoperative score(P<0.05),and there was no significant difference between the two groups 3 days after operation.Oswestry disability index scores of group A at postoperative 3 and 6 months were significantly decreased than preoperative score(P<0.05).The Oswestry disability index scores of group B at postoperative 3 and 6 months did not show significant differences than preoperative score(P>0.05).The comparison between the two groups showed the Oswestry disability index scores of group A were significantly lower than group B at postoperative 3 and 6 months(P<0.05).(4)The results of modified Macnab showed that the excellent and good rate of group A was significantly higher than that of group B(95%,78%,P<0.05).(5)It is indicated that the hybrid technique is a new spinal endoscopy technique,which has the advantages of less trauma and faster recovery as a minimally invasive surgery.The clinical outcome of hybrid technique is superior to that of uniportal endoscopic surgery in the treatment of lumbar spinal stenosis with bilateral symptoms.Additionally,it also has the advantages of good operational flexibility and high decompression efficiency as an open surgery.

BACKGROUND:How to effectively promote bone regeneration and bone reconstruction after bone injury has always been a key issue in clinical bone repair research.The use of biological and degradable materials loaded with bioactive factors to treat bone defects has excellent application prospects in bone repair. OBJECTIVE:To investigate the effect of polylactic acid-glycolic acid copolymer(PLGA)composite scaffold modified by lysine-grafted graphene oxide nanoparticles(LGA-g-GO)on osteogenic differentiation and new bone formation. METHODS:PLGA was dissolved in dichloromethane and PLGA scaffold was prepared by solvent evaporation method.PLGA/GO composite scaffolds were prepared by dispersing graphene oxide uniformly in PLGA solution.LGA-g-GO nanoparticles were prepared by chemical grafting method,and the PLGA/LGA-g-GO composite scaffolds were constructed by blending LGA-g-GO nanoparticles at different mass ratios(1%,2%,and 3%)with PLGA.The micromorphology,hydrophilicity,and protein adsorption capacity of scaffolds of five groups were characterized.MC3T3 cells were inoculated on the surface of scaffolds of five groups to detect cell proliferation and osteogenic differentiation. RESULTS AND CONCLUSION:(1)The surface of PLGA scaffolds was smooth and flat under scanning electron microscope,while the surface of the other four scaffolds was rough.The surface roughness of the composite scaffolds increased with the increase of the addition of LGA-g-GO nanoparticles.The water contact angle of PLGA/LGA-g-GO(3%)composite scaffolds was lower than that of the other four groups(P<0.05).The protein adsorption capacity of PLGA/LGA-g-GO(1%,2%,and 3%)composite scaffolds was stronger than PLGA and PLGA/GO scaffolds(P<0.05).(2)CCK-8 assay showed that PLGA/LGA-g-GO(2%,3%)composite scaffold could promote the proliferation of MC3T3 cells.Alkaline phosphatase staining and alizarin red staining showed that the cell alkaline phosphatase activity in PLGA/LGA-g-GO(2%,3%)group was higher than that in the other three groups(P<0.05).The calcium deposition in the PLGA/GO and PLGA/LGA-g-GO(1%,2%,and 3%)groups was higher than that in the PLGA group(P<0.05).(3)In summary,PLGA/LGA-g-GO composite scaffold can promote the proliferation and osteogenic differentiation of osteoblasts,and is conducive to bone regeneration and bone reconstruction after bone injury.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.

BACKGROUND:Several observational studies have found a close relationship between thyroid function levels and sarcopenia,but the causal relationship between thyroid function levels and the onset of sarcopenia is not yet clear. OBJECTIVE:To investigate the causal relationship between thyroid function levels and sarcopenia using a two sample Mendelian randomization method. METHODS:A two sample Mendelian randomization analysis was conducted using genome-wide association study data on thyrotropin,free triiodothyronine,free tetraiodothyronine,subclinical hyperthyroidism,subclinical hypothyroidism,and four related phenotypes of sarcopenia-lefthand grip strength,right hand grip strength,limb lean mass,and gait speed.The inverse-variance weighted method,weighted median method,simple mode method,weighted median estimator method,and MR Egger regression method were used as analysis methods,while heterogeneity test,pleiotropy test,MR-PRESSO,leave-one-out method,funnel plot and other methods were used for sensitivity analysis. RESULTS AND CONCLUSION:Elevated levels of thyroid-stimulating hormone increased left-(β=0.02,SE=0.01,P=0.01)and right-handed grip strength(β=0.02,SE=0.01,P=0.01),an increase in free triiodothyronine decreased left-(β=-0.06,SE=0.02,P=9.5×10-5)and right-handed grip strength(β=-0.07,SE=0.02,P=9.3×10-5),and subclinical hyperthyroidism decreased gait speed(β=-4.4×10-3,SE=1.7×10-3,P=0.01).The sensitivity analysis results were basically consistent with the main analysis results.To conclude,an increase in thyroid-stimulating hormone is a protective factor for sarcopenia,and elevation of free triiodothyronine and subclinical hyperthyroidism may increase the risk of sarcopenia.

BACKGROUND:Lijin manipulation can promote skeletal muscle repair and treat skeletal muscle injury.However,the formation of fibrosis and scar tissue hyperplasia are closely related to the quality of skeletal muscle repair.To study the regulatory effect of Lijin manipulation on the formation of fibrosis and scar tissue hyperplasia is helpful to explain the related mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury. OBJECTIVE:To explore the mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury in rabbits,thereby providing a scientific basis for clinical treatment. METHODS:Forty-five healthy adult Japanese large-ear white rabbits were randomly divided into blank group,model group and Lijin group,with 15 rats in each group.Gastrocnemius strike modeling was performed in both model group and Lijin group.The Lijin group began to intervene with tendon manipulation on the 3rd day after modeling,once a day,and 15 minutes at a time.Five animals in each group were killed on the 7th,14th and 21st days after modeling.The morphology and inflammatory cell count of gastrocnemius were observed by hematoxylin-eosin staining,the collagen fiber amount was observed by Masson staining,the expression of interleukin-6 and interleukin-10 in gastrocnemius was detected by ELISA.The protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin,alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen were detected by western blot and RT-PCR,respectively,and the expression of type Ⅰ collagen protein was detected by immunohistochemistry. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and Masson staining showed that compared with the model group,inflammatory cell infiltration and collagen fiber content decreased in the Lijin group(P<0.01),and the muscle fibers gradually healed.ELISA results showed that compared with the model group,the expression of interleukin-6 in the Lijin group continued to decrease(P<0.05),and the expression of interleukin-10 increased on the 7th day after modeling(P<0.05)and then showed a decreasing trend(P<0.05).Western blot and RT-PCR results showed that compared with the model group,the protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin in the Lijin group were significantly increased on the 14th day after modeling(P<0.05),but decreased on the 21st day(P<0.05);the protein and mRNA expressions of alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen in the Lijin group were significantly decreased compared with those in the model group(P<0.05).Immunohistochemical results showed that the expression of type Ⅰ collagen in the Lijin group was significantly lower than that in the model group(P<0.05).To conclude,Lijin manipulation could improve the repair quality of skeletal muscle injury by inhibiting inflammation,promoting the proliferation and differentiation of muscle satellite cells,and reducing fibrosis.

BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc. OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of"mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells"in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.

BACKGROUND:The combination of platelet-rich fibrin and autogenous bone has achieved good results in the treatment of periodontal bone defects,but the study of the combination of the two in the treatment of severe alveolar bone defects is scarce. OBJECTIVE:To observe the effect of autologous bone transplantation plus platelet-rich fibrin on the repair of severe alveolar bone defects. METHODS:A total of 102 patients with severe alveolar bone defects in Hengshui People's Hospital from April 2022 to February 2023 were selected and divided into control and observation groups(n=51 per group)by random number table method.Guided tissue regeneration was performed in both groups.The bone defect was filled with autogenous bone in the control group,and the observation group underwent platelet-rich fibrin+autogenous bone filling for bone defects during the operation.The clinical efficacy,changes in tooth mobility,periodontal microecological environment(probing depth,clinical attachment loss,and bleeding index),height and density of alveolar bone,gingival crevicular fluid indicators(transforming growth factor-β,serine protease inhibitor,and matrix metalloproteinase-3)before and after surgery,as well as adverse reactions were observed between the two groups. RESULTS AND CONCLUSION:Six months after operation,there was no significant difference in treatment efficacy rate between the two groups(P>0.05).At 3 and 6 months after surgery,the levels of tooth mobility,probing depth,clinical attachment loss,and bleeding index in the observation group were lower than those in the control group(P<0.05).At 6 months after surgery,the height of alveolar bone in the observation group was higher than that in the control group(P<0.05).At 3 and 6 months after surgery,the levels of transforming growth factor-β in gingival crevicular fluid in the observation group were higher than those in the control group(P<0.05).At 3 and 6 months after surgery,the levels of serine protease inhibitor and matrix metalloproteinase-3 in the observation group were lower than those in the control group(P<0.05).The results suggest that using platelet-rich fibrin+autogenous bone filling in guided tissue regeneration treatment of patients with severe alveolar bone defects can improve the periodontal microenvironment,reduce gingival tissue inflammation,promote alveolar bone tissue regeneration and repair,and reduce tooth mobility.

BACKGROUND:Repetitive trans-spinal magnetic stimulation(rTSMS)can inhibit inflammatory responses following spinal cord injury.rTSMS applies magnetic field stimulation to the spinal cord region to modulate neuronal excitability and synaptic transmission,thereby promoting plasticity and repair of the nervous system. OBJECTIVE:To observe the effects of rTSMS on the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB/NLRP3 signaling pathway after spinal cord injury and explore its mechanism in promoting motor function recovery. METHODS:Male C57BL/6J mice,SPF grade,were randomly divided into sham surgery group,spinal cord injury group,and rTSMS group.The latter two groups of mice were anesthetized and the T9 vertebral plate was removed using rongeur forceps to expose the spinal cord,and the spinal cord was clamped using a small aneurysm clip for 20 seconds to establish the spinal cord injury model.Mice in the rTSMS group underwent a 21-day rTSMS intervention starting on day 1 after spinal cord injury.The stimulation lasted 10 minutes per day,5 days per week with an interval of 2 days.Basso Mouse Scale scores were used to assess motor function recovery in mice after spinal cord injury at 1,3,7,14,and 21 days after spinal cord injury.Western blot was employed to detect the expression of AQP4,apoptotic factors Bax,Bcl-2,CL-Caspase-3,inflammatory factors tumor necrosis factor-α,interferon-γ,interleukin-6,interleukin-4,and the TLR4/NF-κB/NLRP3 signaling pathway related proteins in the injured spinal cord.Oxidative stress assay kit was used to measure the activity of superoxide dismutase,glutathione peroxidase,and malondialdehyde content at the site of spinal cord injury.Immunofluorescence staining was performed to detect the expression of neuronal nuclei(NeuN). RESULTS AND CONCLUSION:The Basso Mouse Scale score in the rTSMS group was significantly higher than that in the spinal cord injury group(P<0.05).Compared with the spinal cord injury group,the rTSMS group showed a reduction in spinal cord water content.The expression of AQP4 protein,malondialdehyde content,and expression of Bax,Bcl-2,CL-Caspase-3,tumor necrosis factor-α,interferon-γ,interleukin-6,and TLR4/NF-κB/NLRP3 signaling pathway related proteins were all decreased in the rTSMS group,while the activities of superoxide dismutase and glutathione peroxidase,as well as the expression of Bcl-2,interleukin-4,and NeuN,were all increased(P<0.05).These results suggest that rTSMS downregulates the expression of proteins related to the TLR4/NF-κB/NLRP3 signaling pathway,alleviating symptoms after spinal cord injury such as spinal cord edema,oxidative stress,apoptosis,and inflammation,exerting neuroprotective effects,and thereby promoting the recovery of hindlimb motor function after spinal cord injury.

ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.