Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences最新文献

Objectives: To explore the causal relationship between ferroptosis-related gene heat shock protein A5 (HSPA5) and hepatocellular carcinoma (HCC).

Methods: A two-sample Mendelian randomization (MR) design was employed to evaluate the causal relationships among HSPA5, regulatory T cells (Tregs), and liver cancer. Single nucleotide polymorphisms (SNPs) associated with HSPA5, HCC and Tregs were selected as instrumental variables through publicly available genome-wide association studies (GWAS) databases. MR analysis was used to assess the direct effect of HSPA5 on HCC, followed by two-step MR to analyze the potential mediating role of Tregs. Reverse MR analysis was conducted with liver cancer as the exposure and HSPA5 as the outcome. Inverse variance weighting (IVW) was the primary method for testing causal associations in all MR analyses. Robustness of the results was confirmed through MR Egger, weighted median, weighted mode, and simple mode methods. Heterogeneity of instrumental variables was evaluated using Cochrane's Q statistic, while pleiotropy was tested by MR-Egger intercept and MR-PRESSO, with leave-one-out sensitivity analysis performed for robustness. Data from The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) were utilized to verify the expression levels of HSPA5 in liver cancer tissues and its correlation with Tregs to reveal the interaction mechanisms between HSPA5 and Tregs in HCC progression and their relationship with patient prognosis.

Results: MR analysis showed a positive correlation between elevated HSPA5 expression and liver cancer risk (all P<0.01), while reverse MR analysis found no statistically significant association between liver cancer and HSPA5 (P>0.05). HSPA5 expression was significantly correlated with Tregs function (all P<0.05), and the enrichment of Tregs in the liver cancer microenvironment was positively associated with liver cancer progression (all P<0.05). Mediation analysis indicated that Tregs accounted for 5.00% and 7.45% of the mediation effect between HSPA5 and liver cancer. TCGA and HPA database analysis revealed that both HSPA5 mRNA and protein expression levels were higher in liver cancer tissues compared to normal tissues, and high HSPA5 expression was significantly associated with poor patient prognosis. Immune infiltration analysis confirmed a significant positive correlation between HSPA5 and Tregs, with high Tregs infiltration closely related to HCC progression.

Conclusions: Elevated HSPA5 expression is significantly associated with HCC development and poor prognosis. HSPA5 may promote HCC progression by regulating the function of Tregs in the tumor microenvironment.

Objectives: To develop a two-dimensional liquid chromatography method to determine the content of vitamin D₃ in cod liver oil preparations.

Methods: The samples were prepared by saponification and extraction, and the content of vitamin D₃ was determined by two-dimensional liquid chromatography with dual-pump-single-valve switching dual detectors. The chromatographic column, capture device, and detection wavelength were optimized; the linearity, system suitability, recovery rate, repeatability and sample stability of the method were investigated, and further validated in actual sample determination.

Results: A column switching two-dimensional chromatography method was developed. In the first dimensional chromatography, an Agilent PoroShell SB-C8 (50 mm×4.6 mm, 2.7 μm) column was used, and acetonitrile-water was used as mobile phase and gradiently eluted at a flow rate of 1.0 mL/min, the detection wavelength was 264 nm. An Agilent Zorbax SB-C18 (150 mm×3.0 mm,1.8 μm) column was used in the second dimensional chromatography, and acetonitrile was used as mobile phase at a flow rate of 0.42 mL/min, the detection wavelength was 264 nm. In determining content of Vitamin D₃, there was a good linear relationship in the concentration range and the system suitability, recovery rate, repeatability and sample stability all met the verification requirements.

Conclusions: The developed two-dimensional liquid chromatography method in the study is accurate, reproducible and simple, it can simultaneously separate pre-vitamin D₃, trans-vitamin D₃, vitamin D₃, and tachysterol3, the baseline separation was achieved, indicating that it is worth promoting for application.

Objectives: To evaluate the immunogenicity and osteogenic ability of animal-derived bone graft material decellularized with supercritical carbon dioxide.

Methods: Porcine femurs were randomly divided into two groups after preliminary treatment, and decellularized with conventional method (conventional control group) or supercritical carbon dioxide (experimental group). Clearance rate of galactose-α-1, 3-galactose (α-Gal) and residual DNA of the two groups were analyzed to assess the immunogenicity of the xenogenic materials. Clearance rate of α-Gal was determined by enzyme-linked immunosorbent assay and residual DNA was detected by fluorescence method. Nine SPF-grade male athymic nude mice of 6 weeks old were randomly divided into experimental group, conventional control group and positive control group. Samples were implanted over biceps femoris muscle of athymic nude mice, the explants were collected 4 weeks post implantation, hematoxylin and eosin (HE) staining and immunohistochemistry were applied to determine the osteogenic ability and bone tissue-associated protein expressions of the implants.

Results: The clearance rates of α-Gal antigen in the experimental group and the conventional control group were (99.09±0.26)% and (30.18±2.02)%, respectively (t=58.67, P<0.01). The residual DNA of the experimental group, the conventional control group and the positive control group were (13.49±0.07) ng/mg, (15.20±0.21) ng/mg and (14.70±0.17) ng/mg, the residual DNA in the experimental group was significantly lower than that in the conventional control group (t=－13.41, P<0.01) and the positive control group (t=－11.30, P<0.01). HE staining showed that multiple bone formation centers with active osteogenesis and rich bone marrow were observed in experimental group 4 weeks after implantation, only a small number of bone formation centers were observed in the conventional control group and the positive control group, with no obvious osteoblasts present. Immunohistochemistry results indicated that the expressions of alkaline phosphatase, Runt-related transcription factor 2, typeⅠcollagen and osteocalcin in the experimental group showed an increasing trend compared with those in the conventional control group and the positive control group.

Conclusions: Compared with clinically used demineralized bone matrix and bone graft material decellularized with conventional method, bone graft material decellularized with supercritical carbon dioxide exhibits lower immunogenicity and better osteogenic ability.

Objectives: To summarize the best evidence for the management of ovarian hyperstimulation syndrome in patients undergoing assisted reproductive therapy.

Methods: Evidence related to the management of ovarian hyperstimulation syndrome in patients undergoing assisted reproductive therapy, including guidelines, clinical decision, best clinical practice, systematic evaluation, expert consensus and evidence summary and related original research were systematically searched in UpToDate, BMJ Best Practice, World Health Organization (WHO) website, Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE) website, National Guidelines website, American Society for Reproductive Medicine (ASRM) website, New York Academy of Sciences (NYAS) website, Joanna Briggs Institute (JBI) database, Cochrane Library, CINAHL, PubMed, Wanfang database, CNKI, and China Biomedical Literature Database from inception to May 31, 2024. Two researchers independently evaluated the quality of the literature, and a senior researcher made the final decision for literature inclusion.

Results: A total of 15 articles were included in the study. Following quality assessment, one article was excluded. The remaining 14 articles included 5 practice guidelines, 3 systematic reviews, 2 expert consensuses, 1 evidence summary, and 3 from UpToDate. Ultimately, 27 pieces of evidence were identified across five key aspects: risk assessment, disease monitoring, early prevention, institutional management and health education.

Conclusions: The updated evidence indicates that the monitoring and prevention of ovarian hyperstimulation syndrome should start early, personalized treatment plans should be provided for patients, and the rational allocation of treatment resources needs to be promoted to enhance effective management of ovarian hyper-stimulation syndrome.

Periodontitis is a chronic inflammatory disease characterized by progressive destruction of alveolar bone. The most critical mechanism underlying alveolar bone destruction is the imbalance of bone homeostasis, where osteoblast-mediated bone matrix synthesis plays an important role in regulating bone homeostasis. Regulated cell death is instrumental in both the inflammatory microenvironment and the regulation of bone homeostasis. Chronic inflammation, oxidative stress, and other factors can be directly involved in mitochondrial and death receptor-mediated signaling pathways, modulating B-cell lymphoma 2 family proteins and cysteine aspartic acid specific protease (caspase) activity, thereby affecting osteoblast apoptosis and alveolar bone homeostasis. Chronic inflammation and cellular damage induce osteoblast necroptosis via the RIPK1/RIPK3/MLKL signaling pathway, exacerbating the inflammatory response and accelerating alveolar bone destruction. Stimuli such as pathogenic microorganisms and cellular injury may also activate caspase-1-dependent or independent signaling pathways and gasdermin D family proteins, promoting osteoblast pyroptosis and releasing pro-inflammatory cytokines to mediate alveolar bone damage. Iron overload and lipid peroxidation in periodontitis can trigger ferroptosis in osteoblasts, impacting their survival and function, ultimately leading to bone homeostasis imbalance. This article focuses on the mechanism of periodontal disease affecting bone homeostasis through regulatory cell death, aiming to provide research evidence for the treatment of periodontitis and alveolar bone homeostasis imbalance.

Microspheres are a novel drug delivery system, which provides a new approach for cancer therapy. Anti-cancer agents loaded in microspheres can be released in a controlled and sustained pattern, thereby enhancing the therapeutic efficacy and reducing the side effects and toxicity. The preparation methods for drug delivery microspheres include solvent evaporation, phase separation, spray drying, and microfluidic technology, each of these have advantages and limitations. Based on the preparation materials, drug delivery microspheres can be categorized into natural polymer microspheres, synthetic polymer microspheres and bioceramic microspheres. Natural polymer micro-spheres have good biocompatibility and degradability; synthetic polymer microspheres exhibit superior mechanical properties; bioceramic microspheres have good biocompatibility and specific biological functions, which are widely used in bone tissue engineering. Drug delivery microspheres are used for cancer treatment in various modalities, including photothermal therapy, photodynamic therapy, radioembolization, and immunotherapy, as well as chemotherapy. This article reviews the recent progress of microspheres as nano drug delivery system in cancer treatment to provide a reference for further clinical and translation research.

Important anatomical structures such as mandibular incisive canal, tongue foramen, and mouth floor vessels may be damaged during implant surgery in the mandibular anterior region, which may lead to mouth floor hematoma, asphyxia, pain, paresthesia and other symptoms. In severe cases, this can be life-threatening. The insufficient alveolar bone space and the anatomical variation of blood vessels and nerves in the mandibular anterior region increase the risk of blood vessel and nerve injury during implant surgery. In case of vascular injury, airway control and hemostasis should be performed, and in case of nerve injury, implant removal and early medical treatment should be performed. To avoid vascular and nerve injury during implant surgery in the mandibular anterior region, it is necessary to be familiar with the anatomical structure, take cone-beam computed tomography, design properly before surgery, and use digital technology during surgery to achieve accurate implant placement. This article summarizes the anatomical structure of the mandibular anterior region, discusses the prevention strategies of vascular and nerve injuries in this region, and discusses the treatment methods after the occurrence of vascular and nerve injuries, to provide clinical reference.

With the rapid development of implant techniques and digital technology, intraoral digital impressions have become a commonly used impression method in implant restoration. At present, the accuracy of intraoral digital impressions directly applied to implant-supported prostheses in edentulous jaw remains inadequate. This is due to the high accuracy requirement of full-arch implant impressions, while there are still technical challenges in intraoral digital impressions about recognition and stitching. In this regard, scholars have proposed a variety of scanning strategies to improve the accuracy of intraoral scans, including mucosal modifications, auxiliary devices and novel scan bodies. At the same time, as a new digital impression technique, stereo photogrammetry has been developing steadily and exhibits promising accuracy. This article reviews the research progress on the accuracy of edentulous full-arch implant impressions and techniques which can improve the accuracy of intraoral digital impressions thus providing a reference for clinical application.

Objectives: To investigate the incidence and influencing factors of allergic reactions to cephalosporins.

Methods: A cross-sectional study of 29 medical institutions in Zhejiang Province was conducted from April 2021 to June 2021. The incidence of allergic reactions to cephalosporins was investigated, and the influencing factors of cephalosporin-induced allergic reactions were analyzed by Poisson regression.

Results: A total of 56 155 patients were included in this study. The total incidence of allergic reactions to cephalosporin was 1.67‰, the highest incidence of anaphylaxis occurred for ceftizoxime (4.27‰), followed by ceftriaxone (3.49‰) and cefotaxime (2.40‰). There was no significant difference in the incidence of allergic reactions between patients with negative skin tests and those without skin tests (1.75‰ vs. 1.63‰, RR=1.07, 95%CI: 0.70-1.63, P>0.05). Poisson regression showed that body mass index (BMI) <18.5 kg/m² (RR=2.43, 95%CI: 1.23-4.82, P<0.05) and history of β-lactam antibiotics allergy (RR=33.88, 95%CI: 1.47-781.12, P<0.05) increased cephalosporin-induced anaphylaxis. Compared with cefuroxime, the risk of allergic reactions was increased for ceftriaxone (RR=3.08, 95%CI: 1.70-5.59, P<0.01), ceftazidime (RR=1.89, 95%CI: 1.03-3.47, P<0.05), and ceftizoxime (RR=3.74, 95%CI: 1.64-8.50, P<0.01).

Conclusions: Lower BMI and history of β-lactam antibiotics allergy increase the risk of cephalosporin allergic reactions. The routine skin test may not reduce the occurrence of allergic reactions to cephalosporins.