Intervertebral disc degeneration （IVDD） is the core cause of chronic low back pain， which severely impairs patients’ quality of life and imposes a heavy social and medical burden. The hypoxia-pyroptosis-inflammation cascade mediated by hypoxia-inducible factor-1α （HIF-1α） is the core pathological mechanism driving the initiation and progression of IVDD. Natural active ingredients derived from traditional Chinese medicine （TCM） have become a research hotspot in the field of IVDD prevention and treatment due to their advantages of multi-target effects， favorable efficacy， and low toxicity. This paper systematically reviews the mechanism of HIF-1α-mediated hypoxia-pyroptosis-inflammation cascade in degenerative nucleus pulposus tissue and the intervention of related active ingredients. It is found that natural active ingredients such as baicalein， curcumin and resveratrol can intervene in the HIF-1α-mediated pathological cascade through four core links to delay IVDD progression： targeting the HIF-1α oxygen sensing pathway to block the initiation of pyroptosis cascade， inhibiting NOD-like receptor protein 3 inflammasome activation to cut off the cascade amplification of inflammatory signals， intervening in the Gasdermin D-mediated pyroptosis execution stage to protect cell membrane integrity， and regulating extracellular matrix metabolism to reconstruct intervertebral disc homeostasis.

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:Multiple clinical observational studies have suggested a close relationship of serum trace elements and nutrients with osteonecrosis,but it remains unclear whether there is a genetic causal effect between serum trace elements and nutrients on osteonecrosis. OBJECTIVE:To investigate the causal effects of serum trace elements and nutrients on osteonecrosis using the Mendelian randomization approach. METHODS:The exposure factors of serum trace elements and vitamins with mononucleotide polymorphisms were obtained from the published UK Biobank database and publicly available databases of genome-wide association studies.The outcome event of osteonecrosis was derived from the FinnGen Biobank database.Mendelian randomization methods were employed to explore the causal relationship between seven trace elements and three nutrients with osteonecrosis.Causal inference was conducted using inverse variance weighting,MR-Egger,and weighted median methods.F-statistic was calculated to ensure the robustness of instrumental variables.Cochran's Q test and leave-one-out method were used for heterogeneity testing.MR-Egger regression and MR-PRESSO were employed for horizontal pleiotropy testing.PhenoScanner database was utilized to remove mononucleotide polymorphisms with horizontal pleiotropy to ensure the reliability of the results. RESULTS AND CONCLUSION:Causal relationships were found between serum selenium,phosphate,vitamin C,vitamin E,and osteonecrosis through Mendelian randomization analysis.Serum selenium,vitamin C,and vitamin E were found to have a protective effect on osteonecrosis,while excessive intake of phosphate increased the risk of osteonecrosis.No heterogeneity or horizontal pleiotropy was observed during the study,and Mendelian randomization statistical power(Power value>80%)indicated the reliability of the aforementioned four results.These findings have important clinical implications for the development of targeted preventive and therapeutic measures for osteonecrosis.

Objective To investigate the clinical efficacy and safety of percutaneous vertebroplasty(PVP)combined with radiofrequency ablation(RFA)for spinal metastases.Methods A computerized retrieval of academic papers concerning the case-control studies(CCS)and randomized controlled trials(RCT)of PVP combined with RFA for spinal metastases from the databases of CNKI,Wanfang,Chinese Biomedical Literature Database(CBM),PubMed,Cochrane Library,Web of science and other databases was conducted.A control group(receiving PVP treatment alone)and a test group(receiving PVP combined with RFA treatment)were established.Newcastle-Ottawa scale(NOS)score was used to evaluate case-controlled trial literature,and the Cochrane risk bias assessment tool was used to evaluate the RCT literature.Results A total of 12 articles(10 CCS articles and 2 RCT articles)including 1 051 patients were included in this analysis.Meta-analysis showed that the recurrence rate of spinal metastases(OR=0.17,95％CI=0.08-0.34,P＜0.001),incidence of complications(OR=0.29,95％CI=0.21-0.41,P＜0.001)and pain visual analog scale(VAS)score(WMD=-1.21,95％CI=-1.64--0.78,P＜0.001)in the test group were significantly lower than those in the control group.The Karnofsky functional status(KPS)score(WMD=14.69,95％CI=-12.25-17.14,P＜0.001)in the test group was remarkably higher than that in the control group,but the long-term efficacy in the test group(OR=1.55,95％CI=0.90-2.68,P=0.12)was not obviously better than that in the control group.Conclusion For the treatment of spinal metastases,PVP combined with RFA has significant clinical short-term efficacy and safety,although its long-term efficacy is not obvious.Due to the limited quantity and quality of the included literature,larger-scale and higher-quality clinical trial studies need to be done before the above conclusions can be further clarified.

Objective:To explore the optimal match degree between thoracolumbar kyphosis (TLK) and lower lumbar lordosis (LLL) in adult spinal deformity (ASD) after correction surgery.Methods:Data of 119 ASD patients (male: 28, female: 91), belonging to the Affiliated Hospital of Jining Medical University (19 cases), the Affiliated Hospital of Shandong University of Traditional Chinese Medicine (11 cases), and the First Medical Center of Chinese PLA General Hospital (89 cases) were reviewed and documented from March 2019 to March 2020. All patients (age, 64.48±8.88 years; range, 45-79 years) underwent the surgical procedure of thoracolumbar fusion with instrumentations were followed up over 24 months (51.68±15.60 months; range, 24-87 months) after surgery. Postoperative proximal interface failure, Oswestry disability index (ODI) score and Scoliosis Research Society-22 (SRS-22) score were recorded for all patients. The immediate match of TLK to LLL postoperatively was calculated as follows: TLM=TLK/LLL. The data of those individuals with excellent improvements in the ODI (>50%) at the final follow-up were recorded and analyzed. Then the mean value and the 95% CI of TLM in those individuals were calculated. All participants were subdivided into three groups according to the 95% CI value of TLM. After the receiver operating characteristic curve (ROC) analyzing, the area under the ROC curve (AUC) was the best cutoff value of TLM. The association of proximal junctional failure (PJF) developing with the abnormal TLM postoperatively was analyzed with logistic regression, and the odds ratio (OR) was calculated. Results:62 patients had significant improvements in ODI (>50%) at the final follow-up, and the mean TLM in those individuals was 0.41 [95% CI (0.2, 0.5)]. All patients were divided into three groups: TLM<0.2 (35 cases), 0.2≤TLM≤0.5 (48 cases) and TLM>0.5 (36 cases). The preoperative TLK (13.87°±16.61°) and T 1 pelvic angle (19.69°±10.55°) in the those patients with TLM<0.2 were the smallest, and those were the largest in those with TLM>0.5 (30.59°±16.68°, 28.30°±14.46°). The individuals with TLM<0.2 still had the smallest TLK (2.89°±1.78°), however, those with TLM>0.5 had the largest TLK (17.13°±12.13°) and the smallest LLL (-26.16°±11.02°) accordingly. Additionally, the ODI and SRS-22 for those with 0.2≤TLM≤0.5 at the final follow-up were the best ( P<0.05). ROC curve analysis results showed that the best cutoff value of TLM was 0.4 (sensitivity=78.9%, specificity=76.2%; AUC=0.802, 95% CI (0.708, 0.896) , P<0.001). During the follow-up after orthopedic surgery, there were 19 patients with postoperative proximal junction failure, including 16 patients in the mismatched group (6 patients in the TLM<0.2 group, 10 patients in the TLM>0.5 group) and 3 patients in the matched group (0.2≤TLM≤0.5 group), with the incidence of 23% (16/71) and 6% (3/48), respectively. The difference was statistically significant (χ 2=5.66, P=0.017). Thoracolumbar mismatch was significantly associated with proximal borderline failure after orthosis [ OR=4.35, 95% CI (1.196, 15.924)]. Conclusion:The abnormal correction in thoracolumbar kyphosis and lower lumbar lordosis may result in mismatch between thoracolumbar segments, which would undermine the quality of life, and increase the incidence of proximal junctional failure developing in those ASD patients underwent long-fusion surgeries. The match between TLK and LLL should be 0.2 to 0.5.

Low back pain (LBP) is closely related to intervertebral disc degeneration (IDD) , spinal canal stenosis, intervertebral disc herniation, osteoarthritis of intervertebral facet joints, ligament and muscle lesions, among which IDD is the key factor causing low back pain. Emerging evidence suggests that a large number of pro-inflammatory cytokines are produced during IDD, and the inflammatory responses induced by these cytokines aggravate the occurrence and development of degeneration. At the molecular level, the mechanism of regulating intervertebral disc metabolism based on signal pathway has become a research hotspot, but the specific pathway mechanism is still unclear. In this paper, according to the crosstalk of NF-κB, TGF-β, MAPK, Wnt/β-catenin, PI3K/AKT/mTOR and other signal pathways, the positive and negative feedback effects of signal pathways on the inflammatory response during disc degeneration will be discussed. To elucidate the pro-inflammatory effects of NF-κB, anti-inflammatory effects of TGF-β and MAPK as well as the potential mechanisms of other pathways, we analyze the internal relationship between the mechanism of IDD and the signal pathway transduction, in order to provide new ideas for the treatment of IDD.