More anterior bone loss in middle vertebra after contiguous two-segment cervical disc arthroplasty.

BACKGROUND: Contiguous two-segment cervical disc arthroplasty (CDA) is safe and effective, while post-operative radiographic change is poorly understood. We aimed to clarify the morphological change of the three vertebral bodies operated on. METHODS: Patients admitted between 2015 and 2020 underwent contiguous two-level Prestige LP CDA were included. The follow-up was divided into immediate post-operation (≤ 1 week), early (≤ 6 months), and last follow-up (≥ 12 months). Clinical outcomes were measured by Japanese Orthopedic Association (JOA) score, visual analogue score (VAS), and neck disability index (NDI). Radiographic parameters on lateral radiographs included sagittal area, anterior-posterior diameters (superior, inferior endplate length, and waist length), and anterior and posterior heights. Sagittal parameters included disc angle, Cobb angle, range of motion, T1 slope, and C2-C7 sagittal vertical axis. Heterotopic ossification (HO) and anterior bone loss (ABL) were recorded. RESULTS: 78 patients were included. Clinical outcomes significantly improved. Of the three operation-related vertebrae, only middle vertebra decreased significantly in sagittal area at early follow-up. The four endplates that directly meet implants experienced significant early loss in length. Sagittal parameters were kept within an acceptable range. Both segments had a higher class of HO at last follow-up. More ABL happened to middle vertebra. The incidence and degree of ABL were higher for the endplates on middle vertebra only at early follow-up. CONCLUSION: Our findings indicated that after contiguous two-segment CDA, middle vertebra had a distinguishing morphological changing pattern that could be due to ABL, which deserves careful consideration before and during surgery.

Aloe-emodin alleviates cerebral ischemia-reperfusion injury by regulating microglial polarization and pyroptosis through inhibition of NLRP3 inflammasome activation.

BACKGROUND: Microglial activation plays a crucial role in injury and repair after cerebral ischemia, and microglial pyroptosis exacerbates ischemic injury. NOD-like receptor protein 3 (NLRP3) inflammasome activation has an important role in microglial polarization and pyroptosis. Aloe-emodin (AE) is a natural anthraquinone compound originated from rhubarb and aloe. It exerts antioxidative and anti-apoptotic effects during cerebral ischemia/reperfusion (I/R) injury. However, whether AE affects microglial polarization, pyroptosis, and NLRP3 inflammasome activation remains unknown. PURPOSE: This study aimed to explore the effects of AE on microglial polarization, pyroptosis, and NLRP3 inflammasome activation in the cerebral infarction area after I/R. METHODS: The transient middle cerebral artery occlusion (tMCAO) and oxygen-glucose deprivation/re-oxygenation (OGD/R) methods were used to create cerebral I/R models in vivo and in vitro, respectively. Neurological scores and triphenyl tetrazolium chloride and Nissl staining were used to assess the neuroprotective effects of AE. Immunofluorescence staining, quantitative polymerase chain reaction and western blot were applied to detect NLRP3 inflammasome activation and microglial polarization and pyroptosis levels after tMCAO or OGD/R. Cell viability and levels of interleukin (IL)-18 and IL-1ß were measured. Finally, MCC950 (an NLRP3-specific inhibitor) was used to evaluate whether AE affected microglial polarization and pyroptosis by regulating the activation of the NLRP3 inflammasome. RESULTS: AE improved neurological function scores and reduced the infarct area, brain edema rate, and Nissl-positive cell rate following I/R injury. It also showed a protective effect on BV-2 cells after OGD/R. AE inhibited microglial pyroptosis and induced M1 to M2 phenotype transformation and suppressed microglial NLRP3 inflammasome activation after tMCAO or OGD/R. The combined administration of AE and MCC950 had a synergistic effect on the inhibition of tMCAO- or OGD/R-induced NLRP3 inflammasome activation, which subsequently suppressed microglial pyroptosis and induced microglial phenotype transformation. CONCLUSION: AE exerts neuroprotective effects by regulating microglial polarization and pyroptosis through the inhibition of NLRP3 inflammasome activation after tMCAO or OGD/R. These findings provide new evidence of the molecular mechanisms underlying the neuroprotective effects of AE and may support the exploration of novel therapeutic strategies for cerebral ischemia.

Modulation of the vitamin D receptor by traditional Chinese medicines and bioactive compounds: potential therapeutic applications in VDR-dependent diseases.

The Vitamin D receptor (VDR) is a crucial nuclear receptor that plays a vital role in various physiological functions. To a larger extent, the genomic effects of VDR maintain general wellbeing, and its modulation holds implications for multiple diseases. Current evidence regarding using vitamin D or its synthetic analogs to treat non-communicable diseases is insufficient, though observational studies suggest potential benefits. Traditional Chinese medicines (TCMs) and bioactive compounds derived from natural sources have garnered increasing attention. Interestingly, TCM formulae and TCM-derived bioactive compounds have shown promise in modulating VDR activities. This review explores the intriguing potential of TCM and bioactive compounds in modulating VDR activity. We first emphasize the latest information on the genetic expression, function, and structure of VDR, providing a comprehensive understanding of this crucial receptor. Following this, we review several TCM formulae and herbs known to influence VDR alongside the mechanisms underpinning their action. Similarly, we also discuss TCM-based bioactive compounds that target VDR, offering insights into their roles and modes of action.

Overloaded vertebral body: a unique radiographic phenomenon following multilevel anterior cervical discectomy and fusion.

PURPOSE: Because previous studies have not focused on postoperative cervical collapse, the purpose of the present study was to introduce the overloaded vertebral body (OVB) phenomenon following multilevel zero-profile anterior cervical discectomy and fusion (ACDF) as well as to investigate its effects on radiographic outcomes. METHODS: We conducted a retrospective study involving patients who underwent ACDF. A total of 55 patients were included in the analysis, including 110 OVB and 110 non-OVB. The evaluated vertebral parameters included the vertebral cross-sectional area (CSA), wedge angle (WA), vertebral height [anterior (AH) and posterior (PH)] and anterior-posterior vertebral diameter [upper (UD) and lower (LD)]. RESULTS: The CSA and WA were significantly lower in the OVB group than in the non-OVB group at 3, 6, and 12 months after surgery as well as at the final follow-up (p < 0.01). The AH of the OVB group was significantly lower at 3, 6, and 12 months after surgery as well as at the final follow-up compared to 1 week after surgery (p < 0.01). CONCLUSIONS: OVB, a new phenomenon following multilevel ACDF, is defined as the cervical vertebral body located in the middle of the surgical segments in multilevel anterior cervical spine surgery. Statistical analysis of vertebral parameters, including CSA, WA, AH, PH, UD, and LD, showed that OVB occurs mainly at the anterior edge of the vertebra and that its largest radiographic manifestation is the loss of height at the anterior edge of the vertebra in the early postoperative period.

Research trends and hotspots of mesenchymal stromal cells in intervertebral disc degeneration: a scientometric analysis.

Mesenchymal stromal cells (MSCs) are important potential candidates for regenerative therapy for intervertebral disc degeneration (IDD). This scientometric study aimed to summarize the main research trends, identify current research hotspots, and measure the networks of the contributors and their scientific productivity. A total of 1102 publications regarding MSC in IDD were recognized from January 2000 to April 2022. The number of records every year followed an overall uptrend with fluctuations. The main trend of research demonstrated the practice of gradually applying MSC-based therapy to IDD with the assistance of advances in biomaterials and IDD pathology. A recent focus on MSC-derived exosomes and notochordal cells was detected. The basic studies in this field were mainly contributed to by Japan, the USA, and European countries, while China dominated in the number of recent publications. Tokai University with Daisuke Sakai was the most productive contributor. Cell biology, tissue engineering, and biomaterials were the categories with deep engagement in research of this field.

Mulberry (Morus alba L.) leaf polysaccharide ameliorates insulin resistance- and adipose deposition-associated gut microbiota and lipid metabolites in high-fat diet-induced obese mice.

Dietary supplements are currently being used to ameliorate metabolic alterations via maintaining gut microflora balance. Mulberry leaf is known as medicine homologous food for its glucose- and lipid-modulating properties. However, the effects of mulberry leaf polysaccharide (MP) on metabolic dysbiosis and gut microbiota are still poorly understood. After extraction and characterization, the beneficial effects of water-soluble MP were evaluated in high-fat diet-induced obese mice. MP treatment could reduce adipose tissue, improve insulin resistance, and alleviate the pathological lesions in colon. Investigation of the underlying mechanism showed that MP modulated gut microbial community by 16S rRNA analysis and reversed the elevation of lipid indexes by plasma lipidomics analysis. Correlation analysis indicated that the abundance of seven key bacterial species and six lipids were closely associated with the metabolic traits, respectively. Overall, MP could ameliorate metabolic disorders, and modify the gut microbiota and lipids. This would greatly facilitate the utilization of MP as a functional food.

Safety and efficacy of the pan-FGFR inhibitor erdafitinib in advanced urothelial carcinoma and other solid tumors: A systematic review and meta-analysis.

Objective: This review aimed to comprehensively analyze the safety and efficacy of erdafitinib in treating advanced and metastatic urothelial carcinoma and other solid tumors. Methods: PubMed, Embase, and ClinicalTrials.gov were searched until 10 February 2022. The safety outcome as adverse events and efficacy outcomes, including objective response rate, stable disease rates, and progressive disease rates, were selected and analyzed by comprehensive meta-analysis version 3.0 and STATA 15.0. Results: The most common all-grade adverse events were hyperphosphatemia, dry mouth, stomatitis, diarrhea, and dysgeusia. The occurrence of ≥3 adverse events was relatively low, and stomatitis and hyponatremia were the most common. Moreover, eye disorders could not be ignored. Efficacy in urothelial carcinoma patients was obviously better than in other solid tumor patients, with a higher objective response rate (0.38 versus 0.10) and lower progressive disease rate (0.26 versus 0.68). All responses occurred in patients with fibroblast growth factor receptor (FGFR) alteration. In those patients, a specific FGFR alteration (FGFR3-TACC3) was observed to have a maximum response. Conclusion: Erdafitinib has satisfactory clinical activity for metastatic urothelial carcinoma and other solid tumors, while the toxicity is acceptable. With more RCTs and combination therapy trials published, erdafitinib will be applied widely.

Sanye Tablet Ameliorates Insulin Resistance and Dysregulated Lipid Metabolism in High-Fat Diet-Induced Obese Mice.

Sanye Tablet (SYT) is a patent prescription widely used in treating T2D and pre-diabetes, especially T2D comorbid with hypertriglyceridemia, for many years in China. However, the underlying mechanism that accounts for the anti-diabetic potential of SYT by regulating lipid-related intermediates remains to be elucidated. This study aimed to investigate the mechanism of SYT on lipid metabolism and insulin sensitivity in high-fat diet (HFD)-induced obese mice by means of combining lipidomics and proteomics. The obese mice models were developed via HFD feeding for 20 consecutive weeks. Mice in the treatment group were given metformin and SYT respectively, and the effects of SYT on body weight, blood glucose, insulin sensitivity, fat accumulation in the organs, and pathological changes in the liver were monitored. Lipid metabolism was examined by lipidomics. Further determination of signaling pathways was detected by proteomics. The biological contributions of the compounds detected in SYT's chemical fingerprint were predicted by network pharmacology. SYT treatment reduced body weight, inhibited viscera and hepatic steatosis lipid accumulation, and prevented insulin resistance. Furthermore, it was found that circulatory inflammatory cytokines were reduced by SYT treatment. In addition, lipidomics analysis indicated that SYT targets lipid intermediates, including diacylglycerol (DAG) and Ceramide (Cer). Mechanistically, SYT positively affected these lipid intermediates by suppressing liver lipogenesis via downregulation of SREBP1/ACC and the JAK/STAT signaling pathway. Our results predicted that astragalin and rosmarinic acid might regulate the JAK-STAT pathway by targeting PIM2 and STAT1, respectively, while paeoniflorin and rosmarinic acid were likely to regulate inflammatory responses by targeting TNFα, IL-6, and IL-4 during T2D. Overall, our study provides supportive evidence for the mechanism of SYT's therapeutic effect on dysregulated lipid metabolism in diabesity.