Causal impact of statins on susceptibility to osteoarthritis: insights from a two-sample Mendelian randomization analysis.

BACKGROUND: Osteoarthritis is a widely prevalent cause of pain and disability among older adults. It is an incurable condition, and most treatments are aimed at alleviating symptoms. AIM: This study aimed to investigate the impact of statins on osteoarthritis by using a two-sample Mendelian randomization approach, using genetic variants associated with statin use as instrumental variables. METHOD: Information on single nucleotide polymorphisms associated with statin medication was obtained from the FinnGen study, and data on osteoarthritis were sourced from the UK Biobank. The inverse variance weighted method was used as the primary analytical approach for the Mendelian randomization analysis. Sensitivity analyses were conducted to evaluate horizontal pleiotropy and heterogeneity. To examine the genetic relationship between statins and osteoarthritis, linkage disequilibrium score regression-based estimates were used. RESULTS: Mendelian randomization analysis indicated a positive effect of statin use on the treatment of osteoarthritis (odds ratio 0.951, 95% confidence interval 0.914-0.99, p < 0.05). This conclusion was supported by various Mendelian randomization methods. Sensitivity analyses revealed no significant directional pleiotropy or influential single nucleotide polymorphisms that could compromise the overall causal inference. Linkage disequilibrium score regression-based estimates suggested a modest genetic correlation between statin use and osteoarthritis (Rg = 0.098, Se = 0.034, p < 0.05), thus reinforcing the robustness of the Mendelian randomization analysis. CONCLUSION: Statins reduce the risk of osteoarthritis, aligning with the results of observational studies. Further research is essential to validate these results and explore the underlying mechanisms in detail.

Effects of dietary ginger (Zingiber officinale) polysaccharide on the growth, antioxidant, immunity response, intestinal microbiota, and disease resistance to Aeromonas hydrophila in crucian carp (Carassius auratus).

Ginger polysaccharides (GP) promote growth and development in fish. However, the effects of GP on crucian carp remain unclear. The present study investigated the effects of GP on the growth performance, immunity, intestinal microbiota, and disease resistance in crucian carp. Four treatment groups were established with different concentrations of GP (0.1 %, 0.2 %, 0.4 %, and 0.8 %). GP was not added as the control group, and the feeding period lasted for 56 d, followed by a 96-h anti-infection treatment using Aeromonas hydrophila. The results showed that dietary GP significantly improved growth performance, especially in the 0.4 % GP group. Furthermore, GP administration notably increased serum lysozyme (LMZ) activity, digestive enzyme performance, and antioxidant capacity of crucian carp. Moreover, dietary inclusion of GP up-regulated the expression of tumour necrosis factor-α (TNF-α), interleukin-8 (IL-8), interferon-γ (IFN-γ), and nuclear factor kappa-B (NF-κB) genes while down-regulating IL-10 and transforming growth factor-ß (TGF-ß) gene expressions, thus promoting liver health in crucian carp. Additionally, incorporating GP into the diet regulated both the diversity and composition of the intestinal microbiota in crucian carp, explicitly enhancing the relative abundance of beneficial bacteria, such as Fusobacteriota and Firmicutes. Therefore, GP reduces the mortality of crucian carp infected with A. hydrophila. In conclusion, this study provides novel insights into the application of dietary GP in cultured fish and evaluates the value of traditional Chinese medicinal polysaccharides against pathogenic bacteria.

Development of two novel on-site detection visualization methods for murine hepatitis virus based on the multienzyme isothermal rapid amplification.

Murine hepatitis virus (MHV) infection is one of the most prevalent types of mice infection in laboratory. MHV could cause death in mice and even interfere with the results in animal experiments. Herein, we developed two isothermal approaches based on the Multienzyme Isothermal Rapid Amplification (MIRA), for rapid detection of MHV in conserved M gene. We designed and screened several pairs of primers and probes and the isothermal fluorescence detector was applied for the exonuclease Ⅲ reverse transcription MIRA (exo-RT-MIRA) assay. To further simplify the workflow, the portable fluorescence visualization instrument, also as a palm-sized handheld system, was used for the naked-eye exo-RT-MIRA assay. The amplification temperature and time were optimized. The assay could be processed well at 42 °C 20 min for the exo-RT-MIRA and the naked-eye exo-RT-MIRA assay. The limit of detection (LoD) of the exo-RT-MIRA assay was 43.4 copies/µL. The LoD of the naked-eye exo-RT-MIRA assay was 68.2 copies/µL. No nonspecific amplifications were observed in the two assays. A total of 107 specimens were examined by qPCR and two assays developed. The experimental results statistical analysis demonstrated that the exo-RT-MIRA assay with the qPCR yielded sufficient agreement with a kappa value of 1.000 (p < 0.0001). The results also exhibited a good agreement (kappa value, 0.961) (p < 0.0001) between the naked-eye exo-RT-MIRA assay and the qPCR assay. In our study, the exo-RT-MIRA assay and the naked-eye exo-RT-MIRA assay presented the possibility of new methods in MHV point-of-testing diagnosis.

High-efficiency single-frequency DBR fiber laser at 1091 nm utilizing a Yb:YAG crystal-derived silica fiber.

A single-frequency distributed Bragg Reflector (DBR) fiber laser operating at 1091 nm was demonstrated by using a Yb:YAG crystal-derived silica fiber (YDSF). The YDSF was prepared via the molten core (MC) method, with a Yb2O3 doping concentration of 5.60 wt.% in the core, resulting in a gain coefficient of 1.45 dB/cm at 1091 nm. Employing 0.8 cm of the YDSF, we attained a single-frequency laser with a maximum output power of 145 mW and a slope efficiency of 31.8%. The laser exhibited an optical signal-to-noise ratio (OSNR) exceeding 71 dB, a linewidth of ∼34 kHz, and a stabilized relative intensity noise (RIN) at -132 dB/Hz for frequencies over 4.5 MHz. The fiber laser could serve as an outstanding seed source for high-power, narrow-linewidth fiber amplifiers operating at 1091 nm.

Genetic influence of meningioma on cisplatin resistance: a Mendelian randomization analysis.

BACKGROUND: Although various aspects of cisplatin resistance have been studied, the impact of genetic variations still needs to be explored. AIM: This study aimed to investigate the impact of cisplatin on meningiomas using a two-sample Mendelian randomization (MR) approach, employing genetic variants associated with cisplatin use as instrumental variables. METHOD: We conducted a two-sample MR analysis using genome-wide association study (GWAS) data. Instrumental variables were derived from single-nucleotide polymorphisms (SNPs) associated with meningioma to estimate the causal relationship with cisplatin resistance. Sensitivity analyses were performed to confirm the findings. RESULTS: Genetic predisposition to meningioma significantly increased the risk of cisplatin resistance (odds ratio (OR): 1.63; 95% confidence interval (CI) 1.44-1.85, P < 0.05). Sensitivity analyses supported the causal link. CONCLUSION: This MR study suggests that genetic predisposition to meningioma increases susceptibility to cisplatin resistance. Further research is needed to uncover the mechanisms behind these causal effects.

Changes in thyroid hormones predict weight regain in patients with obesity who undergo metabolic surgery.

AIM: To investigate the relationship between thyroid function and weight regain in patients with obesity after metabolic surgery. METHODS: This retrospective study enrolled 162 patients who underwent metabolic surgery. Correlations between decreases in thyroid hormone levels and changes in weight, waist circumference (WC) and the Chinese visceral adiposity index (CVAI) were assessed. Binary logistic regression and receiver operating characteristic (ROC) curves were used to identify predictors and clinically useful cut-off values, respectively. RESULTS: The levels of thyroid-stimulating hormone (TSH) and free triiodothyronine (FT3) decreased markedly at 1 year after surgery, as did weight, body mass index (BMI), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, WC and CVAI. Decreases in TSH and FT3 after metabolic surgery were associated with changes in weight, BMI and CVAI. Binary logistic regression and ROC curve analyses confirmed that decreases in TSH can predict good weight loss after metabolic surgery to some extent. Finally, binary logistic regression and ROC curve analyses confirmed that changes in TSH can predict weight regain after metabolic surgery. CONCLUSIONS: Changes in TSH and FT3 after metabolic surgery were correlated with changes in weight and CVAI. Changes in thyroid hormones can predict weight regain in patients with obesity who underwent metabolic surgery.

SpRY-mediated screens facilitate functional dissection of non-coding sequences at single-base resolution.

CRISPR mutagenesis screens conducted with SpCas9 and other nucleases have identified certain cis-regulatory elements and genetic variants but at a limited resolution due to the absence of protospacer adjacent motif (PAM) sequences. Here, leveraging the broad targeting scope of the near-PAMless SpRY variant, we have demonstrated that saturated SpRY mutagenesis and base editing screens can faithfully identify functional regulatory elements and essential genetic variants for target gene expression at single-base resolution. We further extended this methodology to investigate a genome-wide association study (GWAS) locus at 10q22.1 associated with a red blood cell trait, where we identified potential enhancers regulating HK1 gene expression, despite not all of these enhancers exhibiting typical chromatin signatures. More importantly, our saturated base editing screens pinpoint multiple causal variants within this locus that would otherwise be missed by Bayesian statistical fine-mapping. Our approach is generally applicable to functional interrogation of all non-coding genomic elements while complementing other high-coverage CRISPR screens.

OsSRF8 interacts with OsINP1 and OsDAF1 to regulate pollen aperture formation in rice.

In higher plants, mature male gametophytes have distinct apertures. After pollination, pollen grains germinate, and a pollen tube grows from the aperture to deliver sperm cells to the embryo sac, completing fertilization. In rice, the pollen aperture has a single-pore structure with a collar-like annulus and a plug-like operculum. A crucial step in aperture development is the formation of aperture plasma membrane protrusion (APMP) at the distal polar region of the microspore during the late tetrad stage. Previous studies identified OsINP1 and OsDAF1 as essential regulators of APMP and pollen aperture formation in rice, but their precise molecular mechanisms remain unclear. We demonstrate that the Poaceae-specific OsSRF8 gene, encoding a STRUBBELIG-receptor family 8 protein, is essential for pollen aperture formation in Oryza sativa. Mutants lacking functional OsSRF8 exhibit defects in APMP and pollen aperture formation, like loss-of-function OsINP1 mutants. OsSRF8 is specifically expressed during early anther development and initially diffusely distributed in the microsporocytes. At the tetrad stage, OsSRF8 is recruited by OsINP1 to the pre-aperture region through direct protein-protein interaction, promoting APMP formation. The OsSRF8-OsINP1 complex then recruits OsDAF1 to the APMP site to co-regulate annulus formation. Our findings provide insights into the mechanisms controlling pollen aperture formation in cereal species.

Stacking and ridge regression-based spectral ensemble preprocessing method and its application in near-infrared spectral analysis.

Spectral preprocessing techniques can, to a certain extent, eliminate irrelevant information, such as current noise and stray light from spectral data, thereby enhancing the performance of prediction models. However, current preprocessing techniques mostly attempt to find the best single preprocessing method or their combination, overlooking the complementary information among different preprocessing methods. These preprocessing techniques fail to maximize the utilization of useful information in spectral data and restrict the performance of prediction models. This study proposed a spectral ensemble preprocessing method based on the rapidly developing ensemble learning methods in recent years and the ridge regression (RR) model, named stacking preprocessing ridge regression (SPRR), to address the aforementioned issues. Different from conventional ensemble learning methods, the proposed SPRR method applied multiple different preprocessing techniques to the original spectral data, generating multiple preprocessed datasets. These datasets were then individually inputted into RR base models for training. Ultimately, RR still served as the meta-model, integrating the output results of each RR base model through stacking. This approach not only produced diversity in base models but also achieved higher accuracy and lower computational complexity by using a single type of base model. On the apple spectral dataset collected by our team, correlation analysis showed significant complementary information among the data produced by different preprocessing techniques. This provided robust theoretical support for the proposed SPRR method. By introducing the currently popular averaging ensemble preprocessing method in a comparative experiment, the results of applying the proposed SPRR method to six datasets (apple, meat, wheat, olive oil, tablet, and corn) demonstrated that compared to the single preprocessing method and averaging ensemble preprocessing method, SPRR yielded the best accuracy and reliability for all six datasets. Furthermore, under the same conditions of the training and test datasets, the proposed SPRR method demonstrated better performance than the four commonly used ensemble preprocessing methods.

The epigenetic regulators EP300/CREBBP represent promising therapeutic targets in MLL-rearranged acute myeloid leukemia.

Acute myeloid leukemia (AML) with mixed-lineage leukemia (MLL) gene rearrangements (MLL-r) is an aggressive subtype of blood cancer with dismal prognosis, underscoring the urgent need for novel therapeutic strategies. E1A-binding protein (EP300) and CREB-binding protein (CREBBP) function as essential transcriptional coactivators and acetyltransferases, governing leukemogenesis through diverse mechanisms. Targeting EP300/CREBBP holds great promise for treating leukemia with some certain cytogenetic abnormalities. Here, we demonstrated that EP300 and CREBBP are core epigenetic regulators in the pathogenesis of MLL-r AML through assaying the transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). Knocking-out EP300/CREBBP and inhibitor (A-485) treatment depressed the MLL-r cells proliferation, while the MLL wild-type cells remained uninfluenced. We found that the CDK4/RB/E2F axis was downregulated specifically in MLL-r AML cell after A-485 treatment by RNA-seq, western blot and cut-tag analyses. EP300/CREBBP inhibitor selectively exerted potent anti-leukemia activity through blocking the MLL-r-BET complex binding to H3K27Ac modification on critical genes loci, distinct from global histone acetylation. Collectively, our study identified EP300/CREBBP as a critical epigenetic driver of MLL-r leukemia and validated their therapeutic potential through targeting inhibition, offering a promising avenue for improving clinical outcomes in this aggressive leukemia.

A pharmacovigilance study of adverse events associated with polymyxins based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database.

BACKGROUND: Polymyxins have been regarded as last-line treatment for multidrug-resistant gram-negative bacterial infections. Nonetheless, concerns regarding toxicity persist. This study aimed to explore and compare potential adverse events (AEs) between colistin and polymyxin B (PMB). METHODS: Polymyxins-related AEs were retrieved from the U.S. Food and Drug Administration Adverse Event Reporting System between 2004 and 2022. Potential signals were estimated by the reporting odds ratio (ROR), and subgroup analyses were preformed to adjust for potential factors in AEs with significant disproportionality. RESULTS: Analysis of 3,915 records involving 718 patients revealed a higher disproportionality of renal and urinary disorders (ROR 1.62, 95% CI 1.01-2.59) and acute kidney injury (ROR 1.75, 95% CI 1.07-2.87) with colistin treatment. Conversely, colistin exhibited a lower risk for neurotoxicity (ROR 0.47, 95% CI 0.30-0.73). Seven cases of skin hyperpigmentation were reported with PMB, whereas none were reported with colistin. Over 80% of cases involving polymyxin-related AEs occurred during the first two weeks of therapies, with a median onset time of 4.5 days. CONCLUSIONS: Patients received colistin displayed a higher potential risk of nephrotoxicity but a lower risk of neurotoxicity. Clinicians should be vigilant in monitoring the AEs of hyperpigmentation disorders induced by PMB.

Optical-Cavity-Incorporated Colorful All-Solid-State Electrochromic Devices for Dual Anti-Counterfeiting.

The fusion of electrochromic technology with optical resonant cavities presents an intriguing innovation in the electrochromic field. However, this fusion is mainly achieved in liquid electrolyte-based or sol-gel electrolyte-based electrochromic devices, but not in all-solid-state electrochromic devices, which have broader industrial applications. Here, a new all-solid-state electrochromic device is demonstrated with a metal-dielectric-metal (MDM) resonant cavity, which can achieve strong thin-film interference effects through resonance, enabling the device to achieve unique structural colors that have rarely appeared in reported all-solid-state electrochromic devices, such as yellow green, purple, and light red. The color gamut of the device can be further expanded due to the adjustable optical constants of the electrochromic layer. What is more, this device exhibits remarkable cycling stability (maintaining 84% modulation capability after 7200 cycles), rapid switching time (coloration in 2.6 s and bleaching in 2.8 s), and excellent optical memory effect (only increasing by 13.8% after almost 36 000 s). In addition, this exquisite structural design has dual-responsive anti-counterfeiting effects based on voltage and angle, further demonstrating the powerful color modulation capability of this device.

Reservoir Characteristics and Formation Model of the Bauxite Gas Reservoir: The Benxi Formation in the LX Block, Northeast of Ordos Basin, China.

Recently, horizontal well L47-1CH in the Longdong area of the southwestern Ordos Basin made a significant breakthrough in bauxite natural gas exploration, changing the traditional geological understanding that bauxite could not form effective reservoirs. To further explore the exploration and development potential of bauxite natural gas reservoirs in the northeast of the Ordos Basin, it is urgent to carry out basic geological studies. This paper discusses the sedimentary environment, reservoir characteristics, and formation patterns of the bauxite gas reservoirs in the LX Block using trace elements, thin sections, X-ray diffraction, scanning electron microscopy, conventional physical properties, constant pressure mercury, etc. Then, the distribution pattern of bauxite was studied according to the restoration of the karst paleogeomorphology, and the formation model of bauxite was ultimately established. The results show that bauxite developed a clear triple-segment structure vertically, characterized by rich iron at the bottom, high aluminum at the middle, and low iron at the top. The mineral composition of the bauxite section mainly includes diaspore, iron minerals, titanium minerals, and birnessite. The types of pores mainly include intra- and intergranular dissolved pores, matrix-dissolved pores, intercrystalline pores, and microfractures. The porosity ranges from 1.51 to 9.90%, with a relatively good sorting and connectivity of the pore and throat. The bauxite was formed in a hot and humid climate, deposited in a shallow-water tidal flat and lagoon sedimentary environment with oxygen depleted, and experienced oscillatory regression during the deposition process. The thickness of bauxite is significantly controlled by karst paleogeomorphology, and it is mainly distributed at the negative terrain positions of karat pits and karst terraces. The above results can provide a geological basis for the exploration and development of bauxite in the Ordos Basin and similar basins worldwide.

Population Pharmacokinetics of Lamotrigine and Its N2-Glucuronide Metabolite in Chinese Patients with Epilepsy.

BACKGROUND: Lamotrigine is a new antiepileptic drug with substantial interindividual variability in its pharmacokinetics and therapeutic responses. This study aimed to develop population pharmacokinetic (PPK) models of lamotrigine and its N2-glucuronide metabolites for model-informed individualized therapy. METHODS: A total of 353 plasma concentrations from Chinese patients with epilepsy receiving oral lamotrigine were used to develop a population PPK model using a nonlinear mixed effects modeling method. One- and two-compartment models were applied to the nonmetabolite and metabolite model, respectively. Forward addition and backward elimination were used to establish the final model. Model validation was performed using standard goodness-of-fit, bootstrap, visual predictive checks, and normalized prediction distribution errors. Finally, simulations were performed to propose lamotrigine dosages in different situations to achieve trough concentrations within the reference interval (2.5-15 mg/L). RESULTS: For both final population PPK models, coadministration with valproic acid (VPA) or enzyme inducer, and body weight significantly affected lamotrigine clearance. The final models for lamotrigine clearance were and for nonmetabolite and metabolite models, respectively. The precision of the PPK parameters was acceptable, and the models exhibited good predictability. Monte Carlo simulations revealed that the lamotrigine dosage administered to patients combined with an enzyme inducer must be tripled that administered with VPA to reach the target trough concentration. CONCLUSIONS: Variability in the pharmacokinetics of lamotrigine is large. Coadministration of VPA or an enzyme inducer and body weight are the most important factors in lamotrigine clearance in Chinese patients with epilepsy. The developed population PPK models might support further optimization of lamotrigine dosing regimens.

Untargeted LC-MS metabolomics reveals the metabolic responses in the Eriocheir sinensis gills exposed to salinity and alkalinity stress.

In recent years, saline-alkaline aquaculture development has become an important measure for China to expand its fishery development space to ensure food safety. Previous studies have verified that salinity and alkalinity positively influence the quality of Chinese mitten crabs (Eriocheir sinensis). However, the regulatory mechanism of E. sinensis endures saline-alkaline stress which remains obscure. This study investigated the metabolic changes in puberty-molting E. sinensis gills exposed to freshwater (FW), sodium chloride salinity of 5 ppt (SW), and carbonate alkalinity 10.00 mmol/L (AW) for 50 days using untargeted liquid chromatography-mass spectrometry metabolomics (LC-MS). A total of 5802 (positive-ion mode) and 6520 (negative-ion mode) peaks were extracted by LC-MS, respectively. A total of 188 (50 upregulated and 138 downregulated), 141 (94 upregulated and 47 downregulated), and 130 (87 upregulated and 43 downregulated) significantly regulated metabolites (SRMs) were observed in the FW-SW, FW-AW, and SW-AW treatments, respectively, wherein 42 generic SRMs were also found by Venn diagram analysis. Seven of the top 10 SRMs with the highest (variable importance in projection) VIP values were similarly identified in FW-SW and SW-AW. Integrated analysis of key metabolic pathways revealed glycerophospholipid, choline in cancer, phenylalanine, and butanoate metabolism. Overall, significant differences were observed in the metabolites and key metabolic pathways of E. sinensis gill exposed to salinity and alkalinity stress. These results will be helpful in understanding the environmental adaptability of aquatic crustaceans to saline-alkaline water.

Constructing lactylation-related genes prognostic model to effectively predict the disease-free survival and treatment responsiveness in prostate cancer based on machine learning.

Background: Prostate cancer (PCa) is one of the most common malignancies in men with a poor prognosis. It is therefore of great clinical importance to find reliable prognostic indicators for PCa. Many studies have revealed the pivotal role of protein lactylation in tumor development and progression. This research aims to analyze the effect of lactylation-related genes on PCa prognosis. Methods: By downloading mRNA-Seq data of TCGA PCa, we obtained the differential genes related to lactylation in PCa. Five machine learning algorithms were used to screen for lactylation-related key genes for PCa, then the five overlapping key genes were used to construct a survival prognostic model by lasso cox regression analysis. Furthermore, the relationships between the model and related pathways, tumor mutation and immune cell subpopulations, and drug sensitivity were explored. Moreover, two risk groups were established according to the risk score calculated by the five lactylation-related genes (LRGs). Subsequently, a nomogram scoring system was established to predict disease-free survival (DFS) of patients by combining clinicopathological features and lactylation-related risk scores. In addition, the mRNA expression levels of five genes were verified in PCa cell lines by qPCR. Results: We identified 5 key LRGs (ALDOA, DDX39A, H2AX, KIF2C, RACGAP1) and constructed the LRGs prognostic model. The AUC values for 1 -, 3 -, and 5-year DFS in the TCGA dataset were 0.762, 0.745, and 0.709, respectively. The risk score was found a better predictor of DFS than traditional clinicopathological features in PCa. A nomogram that combined the risk score with clinical variables accurately predicted the outcome of the patients. The PCa patients in the high-risk group have a higher proportion of regulatory T cells and M2 macrophage, a higher tumor mutation burden, and a worse prognosis than those in the low-risk group. The high-risk group had a lower IC50 for certain chemotherapeutic drugs, such as Docetaxel, and Paclitaxel than the low-risk group. Furthermore, five key LRGs were found to be highly expressed in castration-resistant PCa cells. Conclusion: The lactylation-related genes prognostic model can effectively predict the DFS and therapeutic responses in patients with PCa.

Risk factors associated with high-dose methotrexate induced toxicities.

INTRODUCTION: High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to identify early risk factors associated with HDMTX-induced toxicities, paving the way for personalized treatment. AREAS COVERED: A systematic review of PubMed and Cochrane databases was conducted for articles from inception to July 2023. Eligible studies included reviews, clinical trials, and real-world analyses. Irrelevant studies were excluded, and manual searches and citation reviews were performed. Factors such as MTX exposure, drug interactions, demographics, serum albumin, urine pH, serum calcium, and genetic polymorphisms affecting MTX transport (e.g. SLCO1B1), intracellular folate metabolism (MTHFR), cell development (ARID5B), metabolic pathways (UGT1A1, PNPLA3), as well as epigenetics were identified. EXPERT OPINION: This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.

From hyperglycemia to intervertebral disc damage: exploring diabetic-induced disc degeneration.

The incidence of lumbar disc herniation has gradually increased in recent years, and most patients have symptoms of low back pain and nerve compression, which brings a heavy burden to patients and society alike. Although the causes of disc herniation are complex, intervertebral disc degeneration (IDD) is considered to be the most common factor. The intervertebral disc (IVD) is composed of the upper and lower cartilage endplates, nucleus pulposus, and annulus fibrosus. Aging, abnormal mechanical stress load, and metabolic disorders can exacerbate the progression of IDD. Among them, high glucose and high-fat diets (HFD) can lead to fat accumulation, abnormal glucose metabolism, and inflammation, which are considered important factors affecting the homeostasis of IDD. Diabetes and advanced glycation end products (AGEs) accumulation- can lead to various adverse effects on the IVD, including cell senescence, apoptosis, pyroptosis, proliferation, and Extracellular matrix (ECM) degradation. While current research provides a fundamental basis for the treatment of high glucose-induced IDD patients. further exploration into the mechanisms of abnormal glucose metabolism affecting IDD and in the development of targeted drugs will provide the foundation for the effective treatment of these patients. We aimed to systematically review studies regarding the effects of hyperglycemia on the progress of IDD.

The Prescription trends and dosing appropriateness analysis of novel oral anticoagulants in ischemic stroke patients: a retrospective study of 9 cities in China.

Background: Novel oral anticoagulants (NOACs) have been recommended by guidelines as the first-line drugs for preventing cardiogenic stroke. We aimed to provide an overview of the prescription trends and dosing appropriateness of NOACs in China. Methods: We conducted a retrospective analysis of NOAC prescriptions using the Hospital Prescription Analysis Cooperation Project data from 2016 to 2022. Various patient features, such as gender, age, city, year, source, department visited, original diagnosis, dosing, cost, and insurance type, were collected and analyzed to examine the trends and dosing appropriateness of NOAC usage in ischemic stroke patients. Results: 62,014 NOAC prescriptions were analyzed, including 16,602 for dabigatran, 45,253 for rivaroxaban, and 159 for apixaban. 85.14% of the patients were aged 65 or above, and tertiary hospitals accounted for 95.97% of NOAC prescriptions. NOAC prescriptions rose from 1828 in 2016 to 13,998 in 2021 but dropped to 13,166 in 2022. The percentage of annual prescriptions for NOACs among stroke patients has increased from 0.05% in 2016 to 0.37% in 2022. Total drug cost increased from ¥704541.18 in 2016 to ¥4128648.44 in 2021, then decreased to ¥1680109.14 in 2022. Prescriptions were divided into 48,321 appropriate and 11,262 inappropriate dosing groups, showing significant differences in medications, age, year, city type, hospital level, source, insurance type, and department visited (all p < 0.001). The median drug cost for inappropriate dosing was higher than for appropriate dosing (¥55.20 VS ¥83.80). The top comorbidities in ischemic stroke patients were atrial fibrillation (35.30%), hypertension (32.75%), and coronary heart disease (16.48%). Conclusion: The application of NOACs in the Chinese population is increasing. Our findings highlight the frequent deviation from labeled dosing of NOACs in clinical practice. Continued efforts are necessary to promote the appropriate use of NOACs according to the standard dosage in the drug insert.

Comparison of the S8 navigation system and the TINAVI orthopaedic robot in the treatment of upper cervical instability.

The objective is to compare the clinical efficacy and safety of the S8 navigation system and the Tinavi orthopaedic surgery robot in the treatment of upper cervical instability. The research methods adopted are as follows. The clinical data of patients with upper cervical instability who underwent surgery from May 2021 to December 2021 were analysed retrospectively. Patients were divided into a navigation group (assisted by the S8 navigation system) and a tinavi group (assisted by the Tinavi robot) according to the auxiliary system used. Computed tomography and digital radiography were performed after the operation. The accuracy of pedicle screw placement was evaluated using the criteria put forward by Rampersaud. Degree of facet joint violation, visual analogue scale score, neck disability index and Japanese orthopaedic association score were recorded and assessed during follow-up examinations in both groups. Record two groups of surgery-related indicators. Record the complications of the two groups. A total of 50 patients were included. 21 patients in the navigation group and 29 in the tinavi group. The results of the study are as follows. The average follow-up time was 12.1 months. There was no significant difference in nail placement accuracy between the navigation and tinavi groups (P > 0.05); however, the navigation group had a significantly higher rate of facet joint violation than that of tinavi group (P < 0.05), and the screws were placed closer to the anterior cortex (P < 0.05). Significantly more intraoperative fluoroscopies were performed in the tinavi group than in the navigation group, and the operation time was significantly longer in the tinavi group than in the navigation group (P < 0.05). The time of single nail implantation, intraoperative blood loss and incision length in navigation group were significantly longer than those in tinavi group. There were no statistically significant differences in other indicators between the two groups (P > 0.05). We come to the following conclusion. The Stealth Station S8 navigation system (Medtronic, USA), which also uses an optical tracking system, and the Tinavi Orthopedic robot have shown the same high accuracy and satisfactory clinical results in the treatment of upper cervical instability. Although the S8 navigation system still has many limitations, it still has good application prospects and is a new tool for spine surgery.