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.

Objective:To retrospectively analyze the efficacy and feasibility of surgical management in patients with cervical dysphagia secondary to Diffuse idiopathic skeletal hyperostosis(DISH)of the cervical spine.Methods:A retrospective analysis was conducted on 6 patients who presented with dysphagia as the primary symptom, were diagnosed with cervical DISH, and underwent surgical treatment in the Department of Otorhinolaryngology Head and Neck Surgery of The Second Xiangya Hospital of Central South University from January 2018 to February 2024. There were 5 males and 1 female, aged from 65 to 78 years (70.2±4.7 years). The duration of dysphagia prior to admission was 13 to 18 months (14.7±2.2 months). All patients had the symptom of dysphagia, and at least one other clinical manifestation of cervical DISH (dyspnea, restricted neck mobility, sleep apnea, odynophagia). One patient had undergone tracheotomy due to laryngeal obstruction before surgery. Surgical intervention was performed after failure of conservative management in all patients. All patients underwent anterior cervical osteophyte resection via the Smith-Robinson approach without concomitant spinal fusion. In the patient with prior tracheotomy for airway obstruction, epiglottoplasty and right arytenoidectomy were performed simultaneously. The swallowing function was evaluated by water swallow test, FEES, M. D. Anderson Dysphagia Inventory. Clinical and imaging evaluations were conducted for follow-uppostoperatively. Preoperative and 30-day post operative data were statistically analyzed using paired samples t-test.Results:Cervical computed tomography revealed osteophyte involvement from C2 to T1 with a median of 4 vertebral segments affected. The most frequently involved vertebral segments were C4-C6 (all 6 patients were involved). The anteroposterior diameter of the most prominent osteophyte was 12.0 to 20.0 mm (16±3.1 mm). The time to resumption of a regular diet was 6 to 20 days(12.7±5.3 days), and the time to remove the nasogastric tube was 8 to 25 days(15.2±6.2 days). In the patient with prior tracheotomy, the tracheostomy tube was successfully decannulated 30 days after initial tube capping following conversion to a metal tube. All cervical DISH-related symptoms except for limited neck mobility improved postoperatively. Both water swallow test and the Rosenbek Penetration-Aspiration Scale showed significant improvement postoperatively. At 30 days postoperatively, MDADI scores significantly improved in all domains: l global (73.33±10.33), emotional (85.56±8.35), functional (83.33±5.89), and physical (82.08±6.60). No major perioperative complications occurred. and the length of hospital stay was 7 to 10 days (7.8±1.2 days). The follow-up time was 12 to 84 months (43.7±27.2 months). All patients maintained sustained symptom relief, with no evidence of osteophyte recurrence during follow-up.Conclusion:Cervical DISH is an under-recognized causes of dysphagia in elderly patients and warrants attention from otolaryngologists. For patients erefractory to conservative treatment, anterior resection of cervical osteophytes via the Smith-Robinson approach is a safe, minimally invasive procedure with favorable short-and long-term outcomes in improving swallowing function.

Objective:To retrospectively analyze the efficacy and feasibility of surgical management in patients with cervical dysphagia secondary to Diffuse idiopathic skeletal hyperostosis(DISH)of the cervical spine.Methods:A retrospective analysis was conducted on 6 patients who presented with dysphagia as the primary symptom, were diagnosed with cervical DISH, and underwent surgical treatment in the Department of Otorhinolaryngology Head and Neck Surgery of The Second Xiangya Hospital of Central South University from January 2018 to February 2024. There were 5 males and 1 female, aged from 65 to 78 years (70.2±4.7 years). The duration of dysphagia prior to admission was 13 to 18 months (14.7±2.2 months). All patients had the symptom of dysphagia, and at least one other clinical manifestation of cervical DISH (dyspnea, restricted neck mobility, sleep apnea, odynophagia). One patient had undergone tracheotomy due to laryngeal obstruction before surgery. Surgical intervention was performed after failure of conservative management in all patients. All patients underwent anterior cervical osteophyte resection via the Smith-Robinson approach without concomitant spinal fusion. In the patient with prior tracheotomy for airway obstruction, epiglottoplasty and right arytenoidectomy were performed simultaneously. The swallowing function was evaluated by water swallow test, FEES, M. D. Anderson Dysphagia Inventory. Clinical and imaging evaluations were conducted for follow-uppostoperatively. Preoperative and 30-day post operative data were statistically analyzed using paired samples t-test.Results:Cervical computed tomography revealed osteophyte involvement from C2 to T1 with a median of 4 vertebral segments affected. The most frequently involved vertebral segments were C4-C6 (all 6 patients were involved). The anteroposterior diameter of the most prominent osteophyte was 12.0 to 20.0 mm (16±3.1 mm). The time to resumption of a regular diet was 6 to 20 days(12.7±5.3 days), and the time to remove the nasogastric tube was 8 to 25 days(15.2±6.2 days). In the patient with prior tracheotomy, the tracheostomy tube was successfully decannulated 30 days after initial tube capping following conversion to a metal tube. All cervical DISH-related symptoms except for limited neck mobility improved postoperatively. Both water swallow test and the Rosenbek Penetration-Aspiration Scale showed significant improvement postoperatively. At 30 days postoperatively, MDADI scores significantly improved in all domains: l global (73.33±10.33), emotional (85.56±8.35), functional (83.33±5.89), and physical (82.08±6.60). No major perioperative complications occurred. and the length of hospital stay was 7 to 10 days (7.8±1.2 days). The follow-up time was 12 to 84 months (43.7±27.2 months). All patients maintained sustained symptom relief, with no evidence of osteophyte recurrence during follow-up.Conclusion:Cervical DISH is an under-recognized causes of dysphagia in elderly patients and warrants attention from otolaryngologists. For patients erefractory to conservative treatment, anterior resection of cervical osteophytes via the Smith-Robinson approach is a safe, minimally invasive procedure with favorable short-and long-term outcomes in improving swallowing function.

Objective:To explore the application of spiral tracheoplasty in the repair of large tracheal defects after the resection of trachea invaded by thyroid cancer.Methods:A retrospective analysis was performed on the clinical data of 11 patients, including 4 males and 7 females, aged from 36 to 67 years old, with large tracheal defects after tracheal resection due to thyroid papillary carcinoma invading the trachea in the Department of Otorhinolaryngology Head and Neck Surgery, Second Xiangya Hospital, Central South University from January 2019 to January 2022. The range of tracheal defects, time of tracheal reconstruction, postoperative complications and airway were recorded, and the patients were followed up for more than 24 months.Results:All patients underwent total thyroidectomy and tracheal resection and spiral reconstruction, and 2 of the cases underwent cricoid cartilage resection on the invaded side of cartilage. The tracheal defect accounted for 40%-60% of the circumference, and the lengths of the tracheal defects were 5.0 cm×7.5 cm and 6-9 tracheal rings, with 2 cases combined with partial defects of the cricoid cartilage. The reconstruction time was 30-60 min, with an average of 41.81 min. Among the 11 patients, 3 had recurrent laryngeal nerve paralysis, and 2 underwent tracheotomy. Four patients presented with hypocalcemia within one month after the operation. Followed up for 24-60 months, no tracheal stenosis occurred, the 2-year survival rate was 100%, the 2-year local control rate of the trachea was 100%, and the 2-year tumor-free survival rate was 81.8%.Conclusion:Spiral tracheoplasty is a safe and effective method that can reduce the tension at the tracheal anastomosis and expand the tracheal cavity, which can be used for tracheal reconstruction after extensive resection of trachea invaded by locally advanced thyroid cancer.

Objective:To explore the application of spiral tracheoplasty in the repair of large tracheal defects after the resection of trachea invaded by thyroid cancer.Methods:A retrospective analysis was performed on the clinical data of 11 patients, including 4 males and 7 females, aged from 36 to 67 years old, with large tracheal defects after tracheal resection due to thyroid papillary carcinoma invading the trachea in the Department of Otorhinolaryngology Head and Neck Surgery, Second Xiangya Hospital, Central South University from January 2019 to January 2022. The range of tracheal defects, time of tracheal reconstruction, postoperative complications and airway were recorded, and the patients were followed up for more than 24 months.Results:All patients underwent total thyroidectomy and tracheal resection and spiral reconstruction, and 2 of the cases underwent cricoid cartilage resection on the invaded side of cartilage. The tracheal defect accounted for 40%-60% of the circumference, and the lengths of the tracheal defects were 5.0 cm×7.5 cm and 6-9 tracheal rings, with 2 cases combined with partial defects of the cricoid cartilage. The reconstruction time was 30-60 min, with an average of 41.81 min. Among the 11 patients, 3 had recurrent laryngeal nerve paralysis, and 2 underwent tracheotomy. Four patients presented with hypocalcemia within one month after the operation. Followed up for 24-60 months, no tracheal stenosis occurred, the 2-year survival rate was 100%, the 2-year local control rate of the trachea was 100%, and the 2-year tumor-free survival rate was 81.8%.Conclusion:Spiral tracheoplasty is a safe and effective method that can reduce the tension at the tracheal anastomosis and expand the tracheal cavity, which can be used for tracheal reconstruction after extensive resection of trachea invaded by locally advanced thyroid cancer.

Objective:To screen differentially expressed proteins(DEPs)in the hippocampus of epileptic rats,pro-viding ideas for further exploring the pathogenesis and drug therapeutic targets of epilepsy.Methods:The epileptic rat model(PTZ group)induced by pentylenetetrazol(PTZ).The protein profiles of hippocampal tissues of the PTZ group and control groups were detected by isobaric tag for relative and absolute quantitation(iTRAQ)combined with LC-MS/MS technology,and the fold changes in the protein expression of the PTZ group versus the control group was considered to be more than 1.5 or less than 0.67,and P＜0.05 was taken as the criteria for screening DEPs.Then DEPs were subjected to bioinformatics analyses such as Gene Ontology(GO)functional annotation and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.Results:A total of 80 proteins showed significantly different expression,which included 39 up-regulated and 41 down-regulated.GO analysis showed that the up-regulated DEPs were mainly involved in biological processes such as cellular response to nerve growth factor stimulus,axon develop-ment,cell surface receptor signaling pathway,neuron migration,actin filament depolymerization,and signal transduc-tion,while down-regulated DEPs were mainly involved in biological processes such as tricarboxylic acid cycle,citrate metabolism process,acetyl-CoA biosynthetic process from pyruvate,oxaloacetate metabolism process,and regulation of focal adhesion assembly.KEGG pathway enrichment analysis showed that up-regulated DEPs were mainly involved in five signaling pathways,including AMPK signaling pathway,regulation of actin cytoskeleton,sphingolipid signaling pathway,phenylalanine metabolism,and insulin signaling pathway;The down-regulated DEPs were mainly involved in six signaling pathways,including the citric acid cycle,carbon metabolism,acetate and dicarboxylate metabolism,meta-bolic pathways,amino acid biosynthesis and amyotrophic lateral sclerosis signaling pathways.Conclusion:DEPs from epileptic hippocampal tissues were screened by iTRAQ proteomics,and the metabolic pathways enriched by bioinformat-ics methods for DEPs may be closely related to the pathogenesis of epilepsy.

Objective The aim of this study is to combine Raman spectroscopy and machine learning techniques to distinguish subgin-gival plaques among three groups of subjects,including patients with chronic periodontitis(CP)and type 2 diabetes mellitus(T2DM),patients with CP alone,and healthy controls.Methods The Raman spectra of the subgingival plaques from 20 patients with CP and T2DM(group A),23 patients with CP alone(group B),and 23 healthy controls(group C)were obtained using a portable Raman spec-trometer.Eight common machine learning algorithms were applied to build models to distinguish the Raman spectra of the three types of subgingival plaques.Results The model identified as optimal for distinguishing the three types of subgingival plaques was linear discri-minant analysis(LDA).The optimal model to distinguish groups A and B is LDA,groups A and C is extra trees(ET),and groups B and C group is LDA.Conclusion The proposed classification model based on Raman spectroscopy and machine learning algorithms can dis-tinguish subgingival plaques among patients with CP and T2DM,with CP alone,and healthy controls.This technique can be used in future clinical practice as a screening or diagnostic tool.

The emergence of regular short repetitive palindromic sequence clusters (CRISPR) and CRISPR- associated proteins 9 (Cas9) gene editing technology has greatly promoted the wide application of genetically modified pigs. Efficient single guide RNA (sgRNA) is the key to the success of gene editing using CRISPR/Cas9 technology. For large animals with a long reproductive cycle, such as pigs, it is necessary to screen out efficient sgRNA
Animals ; CRISPR-Cas Systems/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; Gene Editing ; RNA, Guide/genetics* ; Swine

BACKGROUND: Matrix metal oproteinase inhibitor 1 plays an important role in the inhibition of articular cartilage degeneration and destruction.
OBJECTIVE: To observe the changes of matrix metal oproteinase inhibitor 1 expression level in synovium of knee osteoarthritis rats after treated with penetration needling of long needle.
METHODS: A total of 40 Sprague-Dawley rats were randomly assigned into normal group, penetration needling group, drug group and model group, with 10 rats in every group. 1.6% papain solution was injected into knee joint cavity of Sprague-Dawley rats. 2 weeks later, knee osteoarthritis models were established. Rats in the normal and model groups did not receive any intervention. In the penetration needling group, rats were treated by penetration needling with 0.3 mm×125.0 mm filiform needle. Rats in the drug group were intraarticularly injected with sodium hyaluronate.
RESULTS AND CONCLUSION: (1) Enzyme linked immunosorbent assay: at 4 weeks after treatment, matrix metal oproteinase inhibitor 1 expression in synovial membrane was higher in the normal group than in the model group (P < 0.05). Matrix metal oproteinase inhibitor 1 expression in synovial membrane was higher in the penetration needling group and drug group than in the model group (P < 0.05). (2) Results verified that long needle penetration therapy can effectively increase matrix metal oproteinase inhibitor 1 expression in synovial membrane of knee osteoarthritis model rats.

Objective To explore the clinical application value of the expression levels of serum hypoxia induced factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),carcino-embryonic antigen(CEA)and CA125 in predicting the recurrence or metastasis of colon cancer after radical resection.Methods Totally 123 cases of colon cancer after radical surgery in our hospital from July 2009 to December 2013 were performed the retrospective analysis.The correlation between the serum markers levels with the recurrence or metastasis was dynamically analyzed.Results (1)The HIF-1αand CEA levels after operation in 123 cases of co-lon cancer were decreased significantly compared with before operation;(2)The HIF-1α,CEA and CA125 levels in 39 cases of re-currence or metastasis were significantly increased compared with those in 84 cases of non-recurrence or non-metastasis (P <0.05);(3)in 39 cases of recurrence or metastasis,the HIF-1α and CEA levels in recurrence or metastasis were increased signifi-cantly compared with those after the end of chemotherapy (P <0.05);(4)HIF-1αwas positively correlated to VEGF(P <0.05). Conclusion The serum levels of HIF-1αand CEA in the patients with colon cancer are positively correlated with recurrence or me-tastasis,the dynamically combined detection of serum markers has an important significance for predicting and early find recurrence or metastasis after radical operation in colon cancer.