BACKGROUND:It has been elucidated that downregulation of nuclear enriched abundant transcript 1(NEAT1)inhibits the progression of keloid fibroblasts,but the exact mechanism is not fully understood. OBJECTIVE:To investigate the influences of long non-coding RNA nuclear enriched abundant transcript 1(lncRNA NEAT1)on the proliferation,apoptosis and migration of keloid fibroblasts by regulating the miR-136-5p/ubiquitin-specific protease 4(USP4)axis. METHODS:Keloid fibroblasts were divided into five groups:si-NC group,control check group,si-NEAT1 group,si-NEAT1+miR-136-5p inhibitor group,and si-NEAT1+inhibitor-NC group.qRT-PCR was performed to measure the expressions of NEAT1 and miR-136-5p;cell counting kit-8 assay and EDU staining were performed to measure cell proliferation;flow cytometry was performed to measure apoptosis;scratch-healing experiment was performed to measure cell migration;western blot assay was performed to measure the protein expressions of USP4,p27,Bax,matrix metalloproteinase-9,α-smooth muscle actin,and type I collagen α1 chain;dual-luciferase assay was performed to examine the relationship of NEAT1 with miR-136-5p as well as the relationship of miR-136-5p with USP4. RESULTS AND CONCLUSION:Compared with the si-NC group,the NEAT1 expression,absorbance value at 450 nm,percentage of EDU positive cells,scratch-healing rate,the protein expressions of USP4,matrix metalloproteinase-9,α-smooth muscle actin,and type I collagen α1 chain decreased in the si-NEAT1 group(P<0.05),while the expression of miR-136-5p,apoptosis rate,and the protein expressions of p27 and Bax increased(P<0.05).miR-136-5p inhibitor reversed the effect of silencing NEAT1 on the biological behavior of keloid fibroblasts.There was a targeted regulatory relationship between NEAT1 and miR-136-5p as well as between miR-136-5p and USP4.To conclude,silencing NEAT1 may inhibit the proliferation and migration of keloid fibroblasts and induce apoptosis by regulating the miR-136-5p/USP4 axis..

BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.

BACKGROUND:Osteoarthritis is now considered a metabolic disease.Previous studies have shown that glycolysis plays an important role in the occurrence and development of osteoarthritis.Compound 3k,as a novel small molecule inhibitor of glycolysis,has anti-inflammatory and anti-tumor effects.Therefore,it can target glycolysis and is expected to provide new ideas for the treatment of osteoarthritis. OBJECTIVE:To explore the role of Compound 3k in osteoarthritis caused by glycolytic overactivity based on the hypoxia-inducible factor 1 alpha(HIF-1α)/reactive oxygen species(ROS)pathway. METHODS:ATDC5 chondroblasts at logarithmic growth phase were taken to induce osteoarthritis in an in vitro cellular model by the action of 10 ng/mL interleukin-1β for 24 hours.The cytotoxicity of Compound 3k at different concentrations(0.25,0.5,1,2.5,5,10,15 μmol/L)was detected by cell counting kit-8 assay,and the appropriate concentrations were selected for the subsequent experiments.The chondrocytes were randomly divided into control,model and treatment groups.The model group was induced with 10 ng/mL interleukin 1β,and the treatment group was pre-stimulated with Compound 3k for 2 hours and then co-cultured with interleukin 1β.The proliferation of the cells in each group was detected by the cell counting kit-8 assay;the inflammatory level of the cells in each group was detected by the ELISA kit;the ROS,extracellular lactate and glucose contents were detected using the kit;qRT-PCR and western blot were used to detect the levels of related inflammatory factors,interleukin-6 and tumor necrosis factor-α,glycolysis-related genes glucose transporter protein-1,glyceraldehyde 3-phosphate dehydrogenase,monocarboxylate transporter protein-1 and HIF-1α. RESULTS AND CONCLUSION:Compared with the control group,the model group showed a decrease in cell proliferative activity,active glycolysis level,manifested by an increase in extracellular lactate content(P<0.001)and a decrease in glucose content(P<0.001),interleukin-6(P<0.000 1)and tumor necrosis factor-α(P<0.001).The expression levels of glycolysis-related genes glucose transporter protein-1(P<0.001),glyceraldehyde 3-phosphate dehydrogenase(P<0.001),monocarboxylic acid transporter protein-1(P<0.001)and HIF-1α(P<0.001)in the model group were all up-regulated,accompanied by oxidative stress and overproduction of ROS.Compared with the model group,Compound 3k treatment effectively increased cell proliferation activity and inhibited the level of overactive glycolysis(P<0.001),while suppressing the expression of genes related to inflammation(P<0.001)and glycolysis in osteoarthritic chondrocytes,inhibiting oxidative stress,downregulating the expression level of HIF-1α(P<0.000 1)and decreasing the content of ROS.To conclude,Compound 3k inhibits interleukin-1β induced chondrocyte inflammation,and its mechanism may be related to glycolysis and HIF-1α/ROS mediated oxidative stress.

BACKGROUND:Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury.Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway is closely related to the degree of bladder dysfunction. OBJECTIVE:To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. METHODS:Sixty female Sprague-Dawley rats were randomly divided into sham operation group,model group,Jiawei Chunze Decoction low-dose group,Jiawei Chunze Decoction high-dose group and agonist group.In the sham operation group,the spinal cord was exposed but not transected.In the other groups,the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury.At 24 hours after modeling,the sham operation group and model group were intragastrically given equal volume of normal saline,Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg,respectively,via intragastric administration for 4 weeks,and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg.After 4 weeks of treatment,the maximum bladder capacity,leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics.The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test.The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining.The concentrations of GRP78,CHOP and Caspase-12 in serum were detected by ELISA,and the mRNA and protein expressions of PI3K,Akt,GRP78,CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats in the model group were increased(P<0.05),and the leakage point pressure and bladder contraction frequency were decreased(P<0.05);serum GRP78,CHOP,and Caspase-12 levels were also increased(P<0.05).The arrangement of bladder epithelial cells in the model group was disordered,and there was monocyte infiltration between cells,tissue edema,and detrusor tract atrophy.The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group,while those of GRP78,CHOP and Caspase-12 were increased(P<0.05).Compared with the model group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose,high-dose and agonist groups after 4 weeks of intervention(P<0.05),while the leakage point pressure and bladder contraction frequency were increased(P<0.05);serum GRP78,CHOP,Caspase-12 levels were decreased(P<0.05).The bladder epithelial cells in the three intervention groups were distributed evenly,arranged neatly,with less inflammatory cell infiltration and fuller detrusor muscle bundle.Compared with the model group,the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups,while those of GRP78,CHOP and Caspase-12 were decreased(P<0.05).The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group.To conclude,Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury,and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway,and then alleviating apoptosis.

BACKGROUND:Currently,different methods of model establishment have been derived from different injury modes of spinal cord injury.Traditional physical injury modeling methods have their own advantages and disadvantages,and there is a lack of more effective and stable animal models of spinal cord injury. OBJECTIVE:To establish a reproducible,controllable,trauma-free,low-mortality,more stable,widely applicable,and short-term postoperative care rat model of spinal cord injury. METHODS:Forty Sprague-Dawley rats with similar body mass and ages were randomly divided into a control group and an improved group,with 20 rats in each group.Animal models of spinal cord injury in the control group were constructed using a clip model method,while the improved group used a modified ligation method based on the compression method to make the spinal cord injury models using suture ligation based on fenestration.Postoperative comparisons were made between the two groups,assessing urination behavior,hematuria,pyuria(infection rate),mortality,scoliosis rate and Basso-Beattie-Bresnahan locomotor rating scale scores at 1,3,5,and 7 days after modeling. RESULTS AND CONCLUSION:Compared with the conventional modeling method,the modified ligation method based on the compression method resulted in faster recovery of urination behavior,lower hematuria rate,lower infection rate,lower mortality rate,lower scoliosis rate,and more concentrated and stable Basso-Beattie-Bresnahan scores(all below 2 points within 1 week).This proves that the modified ligation method based on compression is more suitable for the establishment of spinal cord injury models in rats.

BACKGROUND:Deep muscle stimulation has the effects of releasing muscle adhesion,relieving muscle spasm,improving and restoring muscle compliance and elasticity.Electromyographic biofeedback therapy can promote nerve recovery and improve lower limb motor function and gait. OBJECTIVE:To observe the effect of the effect of deep muscle stimulation combined with electromyographic biofeedback therapy on the spasm of the triceps surae and gait changes after stroke by using a digital muscle detector and three-dimensional gait analysis system. METHODS:A total of 72 patients who met the inclusion criteria were selected from the Rehabilitation Department of the First Affiliated Hospital of Guangdong Pharmaceutical University from October 2020 to October 2023.And they were enrolled and randomly divided into two groups(n=36 per group):a control group and a combined group.The control group received routine rehabilitation therapies,electromyographic biofeedback and pseudo deep muscle stimulation,while the combined group received true deep muscle stimulation treatment on the basis of the control group,five times per week,for 4 consecutive weeks.The oscillation frequency and dynamic stiffness of the affected gastrocnemius muscle,active range of motion of the ankle dorsiflexion muscle,electromyographic signal of the tibialis anterior muscle,Fugl-Meyer assessment of the lower limbs,and three-dimensional gait analysis parameters were statistically analyzed before and after treatment in two groups. RESULTS AND CONCLUSION:After treatment,oscillation frequency and dynamic stiffness values of the inner and outer sides of the affected gastrocnemius muscle in both groups of patients were significantly reduced compared with before treatment(P<0.05),and the combined group showed a more significant decrease compared with the control group(P<0.05).The active range of motion of the ankle dorsiflexion muscle,electromyographic signal of the tibialis anterior muscle,and Fugl-Meyer scores after treatment were significantly increased or improved compared with before treatment(P<0.05),while the combined group showed a more significant increase or improvement compared with the control group(P<0.05).In terms of gait parameters,the walking speed,frequency,and stride in both groups of patients were significantly increased compared with before treatment(P<0.05),while the combined group showed a more significant increase compared with the control group(P<0.05).The percentage time of support phase on the healthy side was shortened compared with before treatment(P<0.05),while the combined group showed a more significant decrease compared with the control group(P<0.05).In addition,there was no significant difference between the two groups except for the percentage of healthy side support(P>0.05).To conclude,the combination of deep muscle stimulation and electromyographic biofeedback can effectively alleviate triceps spasm in the short term after stroke,improve ankle dorsiflexion function,enhance lower limb motor function,and improve gait.The treatment effect is significant and worthy of clinical promotion and application.

BACKGROUND:Microcirculation,as the only place for the energy metabolism of body substances,is closely related to the human movement ability.Resistance exercise is an effective way to improve the function of microcirculation,but some studies have also pointed out that blood flow restriction exercise can also improve the function of microcirculation and has the advantages of small load and high safety. OBJECTIVE:To compare the effects of 6-week low-load blood flow restriction exercise and high-intensity resistance exercise on the thigh microcirculation function of athletic young men,and to explore the possible mechanism by which exercises improve microcirculation function from the perspective of vascular endothelial function. METHODS:Sixty sports students from Hubei Minzu University were divided into control group,high-intensity resistance exercise group and low-load blood flow restriction exercise group according to the random number table method,with 20 students in each group.The low-load blood flow restriction exercise group performed a low-load blood flow restriction exercise for 6 weeks(three times a week,90 minutes each,at an exercise intensity of 30%1RM).The high-intensity resistance exercise group received a high-intensity resistance exercise for 6 weeks(three times a week,90 minutes each,at an exercise intensity of 70%1RM).The control group did not perform any form of exercise training during this period.Microcirculatory blood perfusion,transcutaneous partial pressure,muscle oxygen saturation,nitric oxide,endothelial nitric oxide synthase,endothelin 1,vascular endothelial cell growth factor,thigh circumference,and muscle strength were tested in each group on the day before the intervention and the morning after the end of the 6-week intervention. RESULTS AND CONCLUSION:After the exercise intervention,heating values of microcirculatory blood flow perfusion and blood cell movement speed in the low-load blood flow restriction exercise group and the high-intensity resistance exercise group were significantly different from those in the control group and before the exercise intervention(P<0.05).The heating values of microcirculatory blood flow perfusion and blood cell movement speed showed significant differences between the low-load blood flow restriction exercise group and the high-intensity resistance exercise group(P<0.05).After the exercise intervention,the levels of nitric oxide,endothelial nitric oxide synthase,endothelin 1,and vascular endothelial cell growth factor were significantly different in the low-load blood flow-limiting exercise group and the high-intensity resistance exercise group compared with the control group and the pre-exercise intervention(P<0.05).After the exercise intervention,thigh circumference and thigh muscle strength were significantly different in low-load blood flow restriction group and high-intensity resistance exercise groups compared with the pre-exercise intervention(P<0.05).All these findings indicate that 6-week low-load blood flow restriction exercise and high intensity resistance exercise may regulate the secretion of vascular factors such as endogenous nitric oxide synthase,endothelin-1 and vascular endothelial growth factor to improve the function of thigh microcirculation and increase the contractile strength of the thigh muscle.In addition,And low-load blood flow restriction exercise has better intervention effects on microcirculatory blood perfusion volume and blood cell movement speed,so low-load blood flow restriction exercise is more advantageous than high-intensity resistance exercise in improving microcirculation function.

BACKGROUND:Traumatic brain injury is a condition in which the normal function of the brain is disrupted by a bump or impact to the head.It is necessary to find effective treatments and objective targets that can help doctors diagnose the injury status and restore the brain function of patients. OBJECTIVE:To explore the effect of electroacupuncture combined with low-frequency transcranial ultrasound stimulation on the electroencephalographic signals of rats with traumatic brain injury. METHODS:Forty 6-week-old SPF male Sprague-Dawley rats were randomly divided into five groups:sham group,model group,electroacupuncture group,low-frequency transcranial ultrasound stimulation group and combined group(electroacupuncture+low-frequency transcranial ultrasound stimulation),with eight rats in each group.Feeney weight-drop method was used to establish the animal model of traumatic brain injury.In the sham group,the bone window was only opened without impact.Interventions were started at 1 day after modeling.Electroacupuncture in the electroacupuncture group,low-frequency transcranial ultrasound stimulation in the low-frequency transcranial ultrasound stimulation group,and electroacupuncture+low-frequency transcranial ultrasound stimulation in the combined group were performed for days in total.The modified neurological severity scale score for assessing rats'neurological deficits was performed at 8 hours after modeling.The percentage of spontaneous alternation behavior in the Y-maze was measured at 7 days after modeling.Then,the electroencephalographic signals were collected and electroencephalographic data of α,β,θ,and δ waves were extracted by fast Fourier transform,and the value of oscillation amplitude and energy ratio were calculated in α,β,θ,and δ waves,as well as the Lempel-Ziv complexity and sample entropy. RESULTS AND CONCLUSION:Compared with the sham group,the modified neurological severity scale scores in the model group,electroacupuncture group,low-frequency transcranial ultrasound stimulation group and combined group were significantly increased at 8 hours after modeling(P<0.05).Compared with the sham group,the value of oscillation amplitude in δ wave and the value of δ energy ratio were significantly increased in the model group at 7 days after modeling,meanwhile the percentage of spontaneous alternation behavior in Y-maze,and the value of α/β energy ratio,Lempel-Ziv complexity,and sample entropy were significantly decreased(P<0.05).Compared with the model group,the value of oscillation amplitude in α and δ waves was significantly decreased in the combined group(P<0.05),while the value of α/β energy ratio was significantly increased(P<0.05)and the value of δ energy ratio was significantly decreased(P<0.05)in the electroacupuncture group,low-frequency transcranial ultrasound stimulation group and combined group.Compared with the electroacupuncture group and low-frequency transcranial ultrasound stimulation group,the value of δ energy ratio was significantly decreased in the combined group(P<0.05),while the percentage of spontaneous alternation behavior,the value of α/β energy ratio,the Lempel-Ziv complexity,and the sample entropy were significantly increased(P<0.05).To conclude,abnormal electroencephalographic signals can appear in rats with traumatic brain injury,while the electroacupuncture combined with low-frequency transcranial ultrasound stimulation can alleviate the abnormal electroencephalographic signals in rats,which suggests the electroencephalographic frequency domain value and nonlinear features can be used to assess the severity of traumatic brain injury.

BACKGROUND:The sports medicine community has widely called for the use of machine learning technology to efficiently process the huge and complicated sports data resources,and construct intelligent sports injury prediction models,enabling accurate early warning of sports injuries.It is of great significance to comprehensively summarize and review such research results so as to grasp the direction of early warning model improvement and to guide the construction of sports injury prediction models in China. OBJECTIVE:To systematically review and analyze relevant research on sports injury prediction models based on machine learning technology,thereby providing references for the development of sports injury prediction models in China. METHODS:Literature search was conducted on CNKI,Web of Science and EBSCO databases,which mainly searched for literature related to machine learning techniques and sports injuries.Finally,61 articles related to sports injury prediction models were included for analysis. RESULTS AND CONCLUSION:(1)In terms of external risk feature indicators,there is a lack of competition scenario indicators,and the inclusion of related feature indicators needs to be further improved to further enrich the dimensions of the dataset for model training.In addition,the inclusion feature weighting methods of the sports injury prediction model are mainly based on filtering methods and the use of embedding and wrapping weighting methods needs to be strengthened in order to enhance the analysis of the interaction effects of multiple risk factors.(2)In terms of model body training,supervised learning algorithms become the mainstream choice.Such algorithms have higher requirements for the completeness of sample labeling information,and the application scenarios are easily limited.Therefore,the application of unsupervised and semi-supervised algorithms can be increased in the later stage.(3)In terms of model performance evaluation and optimization,the current studies mainly adopt two verification methods:HoldOut crossover and k-crossover.The range of AUC values is(0.76±0.12),the range of sensitivity is(75.92±11.03)%,the range of specificity is(0.03±4.54)%,the range of F1 score is(80.60±10.63)%,the range of accuracy is(69.96±13.10)%,and the range of precision is(70±14.71)%.Data augmentation and feature optimization are the most common model optimization operations.The accuracy and precision of the current sports injury prediction model are about 70%,and the early warning effect is good.However,the model optimization operation is relatively single,and data augmentation methods are often used to improve model performance.Further adjustments to the model algorithm and hyperparameters are needed to further improve model performance.(4)In terms of model feature extraction,most of the internal risk profile indicators included are mainly based on anthropometrics,training load,years of training,and injury history,but there is a lack of sports recovery and physical function indicators.

BACKGROUND:Muscle aging is closely related to various epigenetic changes,and exercise has a certain regulatory effect on these epigenetic changes.However,the specific mechanism is not fully understood. OBJECTIVE:To review the epigenetic mechanisms of skeletal muscle and how exercise can improve skeletal muscle aging and promote adaptive changes in muscle through these epigenetic mechanisms,aiming to provide a more comprehensive understanding of skeletal muscle aging and disease mechanisms. METHODS:During the period from June 1st to August 1st,2023,literature searches were conducted for relevant literature published from database inception to August 2023 in databases including Web of Science,PubMed,CNKI,WanFang,and VIP.The search terms used included"skeletal muscle,""muscle,""aging,""older adult,""aging,""exercise,""physical exercise,""epigenetic,"and"epigenetics"in Chinese as well as"skeletal muscle,muscle,aging,older adult,senescence,age,exercise,sports,physical activity,epigenetic,epigenetics"in English.Boolean logic operators were used to connect the search terms for retrieval,and corresponding strategies were developed.According to the predetermined inclusion and exclusion criteria,70 eligible articles were selected. RESULTS AND CONCLUSION:Epigenetics refers to the phenomenon where gene expression and function are regulated without changes in gene sequence,and epigenetic changes in skeletal muscle are an important field.The epigenetic mechanisms of skeletal muscle play an important role in muscle aging,mainly involving DNA methylation,histone modification,regulation of non-coding RNAs,chromatin remodeling,changes in mitochondrial function and expression changes of aging-related genes.Exercise significantly regulates the epigenetics of skeletal muscle,including promoting DNA methylation,muscle histone modification,regulating miRNA expression,and regulating lncRNA expression,regulating muscle factors(such as interleukin-6),regulating mitochondrial function(such as peroxisome proliferators-activated receptors γ co-activator 1α).Future studies are recommended for long-term,cross-diverse population-based exercise interventions;the application of multi-omics techniques such as proteomics and metabolomics;strengthening the understanding of epigenetic changes at the single-cell level;cross-species comparative studies as well as human clinical trials for the translation of animal model findings to humans;strategies for combining exercise and pharmacological interventions to assess their synergistic effects;and epigenetic studies of crosstalk interactions between skeletal muscle and different organs.