OBJECTIVE: To explore prevalence, incidence and possible factors of immediate herniated discs after posterior cervical expansive open-door laminoplasty (EODL). METHODS: Totally 29 patients with cervical spinal stenosis and intervertebral disc herniation who underwent EODL from October 2020 to December 2021 were collected, including 24 males and 5 females, aged from 43 to 81 years old with an average of (61.3±9.0) years old;the courses of disease ranged from 1 to 120 months with an average of (36.4±37.0) months. Three or more intervertebral discs on C₃-C₇ were observed. The clinical efficacy was evaluated according to Japanese Orthopaedic Association (JOA) score before operation, 3 days and 1, 3, 6 and 12 months after operation, respectively. The changes of herniated disc before and after operation were measured by multipoint area method and two-dimensional distance method, and incidence and percentage of herniated disc regression were further calculated. Cervical imaging parameters such as Cobb angle (C₃-C₇), intervertebral angle, T₁ slope (T₁S), spinal canal sagittal diameter, K-line angle, dural sac sagittal diameter were measured and compared before and after operation. Pearson correlation was used to analyze correlation between cervical sagittal imaging parameters and disc herniation changes before and after operation. RESULTS: All patients obtained grade A wound healing, and 14 of them were followed up for 3(1.00, 5.25) months. There were no immediate or long-term postoperative complications. Totally 101 herniated intervertebral discs were measured, of which 79 regression numbers were obtained by area measurement. The number of intervertebral disc regressions by distance measurement was 77. There was no statistically significant difference in Cobb angle, intervertebral angle, T₁S and K-line angle of C₃-C₇ (P>0.05), however, there were statistically significant differences in sagittal diameter of spinal canal, sagittal diameter of dural sac, and JOA score before and after operation(P<0.05). The regression ratio of disc herniation ranged from 5% to 50%, and regression ratio of disc herniation was greater than 25% in 45.57%(36/79). Disc herniation in C_4,5 was positively correlated with sagittal plane diameter in C₅(r=0.423, P=0.028). There was a negative correlation between changes of C_3,4 and C_3,4 intervertebral angle (r=-0.450, P=0.041). The improvement rate of cervical JOA score immediately after operation was (59.54±15.07) %, and postoperative follow-up improved to (76.57±14.66) %. CONCLUSION Herniated disc regression immediately after EODL is a common occurrence, and EODL should be selected as far as possible under the premise of satisfying surgical indications. The regression of disc herniation is positively correlated with spinal canal sagittal diameter, and spinal canal should be enlarged as far as possible in the appropriate scope during EODL, so as to create more opportunities and conditions for disc regression and achieve better clinical results.
Humans ; Female ; Male ; Intervertebral Disc Displacement/diagnostic imaging* ; Spinal Stenosis/diagnostic imaging* ; Laminoplasty/methods* ; Middle Aged ; Aged ; Cervical Vertebrae/diagnostic imaging* ; Adult ; Aged, 80 and over ; Intervertebral Disc/surgery*

OBJECTIVES: To study clinical manifestations and gene mutation features of neonates with centronuclear myopathy. METHODS: A retrospective analysis was conducted on the medical data of 5 neonates with centronuclear myopathy diagnosed in the Neonatal Intensive Care Unit of Children's Hospital, Zhejiang University School of Medicine from January 2020 to August 2024. The data included gender, gestational age, birth weight, Apgar score, clinical manifestations, creatine kinase level, electromyography, genetic testing results and the outcomes of the infants. RESULTS: All 5 male neonates had a history of postpartum asphyxia and resuscitation. They all presented with hypotonia, myasthenia, and respiratory failure; two neonates also had swallowing dysfunction. Of the five neonates, three had normal creatine kinase levels, while two had slightly elevated levels. Electromyography was performed for three neonates, among whom two had myogenic damage. MTM1 gene mutations were identified by genetic testing in all five neonates, including two nonsense mutations and three missense mutations, among which one variant had not been previously reported. Four mutations were inherited from the mother, and the other one was a de novo mutation. The five neonates showed no clinical improvement following treatment, failed weaning from mechanical ventilation, and ultimately died after withdrawal of life-sustaining therapy. CONCLUSIONS Centronuclear myopathy caused by MTM1 gene mutation often has a severe phenotype and a poor prognosis, and it should be considered for neonates with hypotonia and myasthenia after birth. Genetic testing should be performed as soon as possible.
Humans ; Myopathies, Structural, Congenital/genetics* ; Male ; Infant, Newborn ; Retrospective Studies ; Mutation ; Female ; Protein Tyrosine Phosphatases, Non-Receptor/genetics*

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) against cholestatic liver fibrosis in mice. METHODS: BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells (HSCs). HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation (BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues. RESULTS: BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore, BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell (HSC) activation and collagen fiber formation. CONCLUSION The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
Animals ; Mice ; Mesenchymal Stem Cell Transplantation ; Liver Cirrhosis/etiology* ; Male ; Cholestasis/therapy* ; Mice, Inbred C57BL ; Hepatic Stellate Cells ; Mesenchymal Stem Cells

A nodule in the right middle lobe of the lung was treated by a combination of cone-beam CT,three-dimensional registration for fusion imaging,and electromagnetic navigation bronchoscopy-guided thermal ablation.The procedure lasted for 90 min,with no significant bleeding observed under the bronchoscope.The total radiation dose during the operation was 384 mGy.The patient recovered well postoperatively,with only a small amount of blood in the sputum and no pneumothorax or other complications.A follow-up chest CT on the first day post operation showed that the ablation area completely covered the lesion,and the patient was discharged successfully.
Humans ; Bronchoscopy/methods* ; Catheter Ablation/methods* ; Cone-Beam Computed Tomography ; Electromagnetic Phenomena ; Imaging, Three-Dimensional ; Lung Neoplasms/diagnostic imaging* ; Tomography, X-Ray Computed

Objective:To investigate the expression of heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) in human esophageal cancer tissues and its clinical significance.Methods:Single-cell data for esophageal cancer were downloaded from the Gene Expression Omnibus (GEO) database (GSE160269 dataset, last updated on November 29, 2020) to analyze the expression of HNRNPA2B1. Transcriptional sequencing data for esophageal cancer from The Cancer Genome Atlas (TCGA) database, including the fragments per kilobase of transcript per million mapped reads (FPKM) quantitative data (173 samples, consisting of 162 esophageal cancer tissues and 11 adjacent normal tissues), and survival data in the phenotype category were downloaded. Analysis of FPKM quantitative data from the TCGA database for esophageal cancer was performed. The top 250 genes most correlated with HNRNPA2B1 were selected and the R4.3.0 clusterProfiler package was used to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the selected gene set. FPKM quantitative data from the TCGA database for esophageal cancer were imported into the CIBERSORTx website to obtain immune cell abundance scores, and the correlation between HNRNPA2B1 and the degree of immune cell infiltration was analyzed. The clinicopathological data of patients from esophageal cancer tissue microarrays including 114 cases of esophageal squamous cell carcinoma tissues and 66 cases of adjacent normal tissues were collected. The patients underwent surgery from January 2006 to December 2008, and the follow-up period extended until July 2015. Cytokeratin (CK) and HNRNPA2B1 expression in esophageal cancer tissue microarrays were detected by using multi-color immunohistochemical (mIHC) staining, and multispectral tissue imaging was conducted. The R4.3.0 survival package and survminer package in TCGA database were used to calculate the optimal cut-off value of HNRNPA2B1 expression and the proportion of CK + HNRNPA2B1 + cells in tissue microarrays was used to calculate the cut-off value of HNRNPA2B1 expression based on which patients were categorized into high and low expression groups. The overall survival (OS) of both groups was compared and the factors influencing OS were analyzed by using the Cox proportional hazards model. Results:In the GSE160269 dataset of single-cell data for esophageal cancer, the expression level of HNRNPA2B1 in tumor epithelial cells was higher than that in normal epithelial cells, and HNRNPA2B1 was highly expressed in various immune cell subtypes. The high expression level of HNRNPA2B1 was positively correlated with regulatory T cells, naive B cells and memory CD4 + T cells. GO enrichment analysis revealed that HNRNPA2B1 was primarily involved in the biological process of nuclear division, cellular components were mainly enriched in chromosomal regions, and molecular functions were mainly enriched in ATP hydrolysis activity. KEGG enrichment analysis indicated that HNRNPA2B1 was primarily involved in biological processes such as the cell cycle, spliceosome, and DNA replication. Results from mIHC and multispectral tissue imaging demonstrated that CK was predominantly expressed in the cell membranes of tumor cells and normal esophageal epithelial cells, while HNRNPA2B1 was primarily expressed in the nuclei of tumor cells and normal esophageal cells. The expression level of HNRNPA2B1 in esophageal cancer tissues was higher than that in the normal paracancerous tissues ( U = 2 984.00, P < 0.05). Results of tissue microarrays and the survival analysis on the data in the TCGA database indicated that esophageal cancer patients with low HNRNPA2B1 expression had a better OS compared to those with high expression (both P < 0.05). Cox multivariate regression analysis revealed that age ( HR = 1.919, 95% CI: 1.158-3.182, P = 0.011), TNM stage ( HR = 2.404, 95% CI: 1.374-4.207, P = 0.002), T stage ( HR = 2.349, 95% CI: 1.150-4.789, P = 0.019), and the expression of HNRNPA2B1 in tumor epithelial cells ( HR = 2.160, 95% CI: 1.280-3.647, P = 0.004) were independent factors influencing OS in esophageal cancer patients. Conclusions:The high expression of HNRNPA2B1 protein in esophageal cancer tissues may play a role in the developement and progression of esophageal cancer, serving as a crucial biological indicator for prognostic assessment of esophageal cancer.

Objective To investigate the effect of intrarectal local anesthesia (IRLA) with heated oxybuprocaine gel on pain during transrectal ultrasound guided prostate biopsy (TRUSPB).Methods A total of 150 cases patients who underwent TRUSPB in Huzhou Central Hospital from January to June 2023 were prospectively taken into.The patients were randomly divided into group A (routine group),group B (oxybuprocaine gel for IRLA at room temperature) and group C (oxybuprocaine gel for IRLA at 40℃),with 50 cases in each group.Nurses who were unaware of the anesthesia type used visual analog scale (VAS) to score the pain level of patients at each stage (VAS Ⅰ:when the ultrasound probe was inserted into the rectum;VAS Ⅱ:during the biopsy;VAS Ⅲ:30 minutes after biopsy),and the incidence of complications after biopsy were compared.Results The VAS Ⅱ score of group C was lower than that of group A and group B,and the difference was statistically significant (P<0.05).There was no statistically significant difference (P>0.05) in the VAS Ⅰ,VAS Ⅲ scores,and incidence of complications after biopsy among the three groups.There was no allergic reaction to oxybuprocaine gel.Conclusion In TRUSPB,IRLA with heated oxybuprocaine gel can effectively control pain without increasing incidence of complications.