Inflammatory bowel disease(IBD)is a non-specific chronic inflammatory bowel condition.Crohn's disease(CD)and ulcerative colitis(UC)are the 2 main types of IBD.IBD is prone to recurrent attacks,which is associated with many factors,such as immune dysfunction,intestinal microenvironment homeostasis imbalance,and environmental and genetic factors;however,its specific pathogenesis is still unclear.Zebrafish has recently emerged as an emerging animal model and have been used extensively for mechanistic research into IBD,model construction,activity evaluation,and screening of anti-IBD agents,due to their unique biological advantages.Based on the latest research progress using zebrafish in the field of IBD,this review systematically introduces the intestinal development characteristics,tissue structure,intestinal immunity,IBD model,and the application of drug screening in zebrafish,to demonstrate the value of zebrafish in the study of IBD.

A 62-year-old female patient underwent medical thoracoscopic pleural biopsy for undiagnosed pleural effusion. Preoperative vital signs in the patient were stable, with no cardiovascular, cerebrovascular or neurological underlying diseases. During the procedure, midazolam 2 mg (0.045 mg/kg) and fentanyl 150 μg (3.3 μg/kg) were administered by intravenous injection for sedation and analgesia. Two minutes later, the patient developed respiratory depression, and her oxygen saturation decreased to 42%. Immediate jaw thrust maneuver followed by bag-valve-mask ventilation was initiated, and the spontaneous respiration resumed and oxygen saturation recovered (>90%) after 2 minutes, allowing successful biopsy of a pleural nodule. The patient was fully conscious in the immediate postoperative period, with normal ability of communication and mobility. However, at 6 hours postoperatively, she developed anterograde and retrograde amnesia, disorientation, sensation disorders, nausea, and retching. Cranial magnetic resonance imaging revealed no significant abnormalities. These symptoms were considered to be related to transient higher cortical dysfunction induced by the sedative and analgesic agents. Given supportive treatments including fluid administration, the symptoms were gradually improved at 8 hours postoperatively, and resolved completely by 11 hours postoperatively.

Inflammatory bowel disease(IBD)is a non-specific chronic inflammatory bowel condition.Crohn's disease(CD)and ulcerative colitis(UC)are the 2 main types of IBD.IBD is prone to recurrent attacks,which is associated with many factors,such as immune dysfunction,intestinal microenvironment homeostasis imbalance,and environmental and genetic factors;however,its specific pathogenesis is still unclear.Zebrafish has recently emerged as an emerging animal model and have been used extensively for mechanistic research into IBD,model construction,activity evaluation,and screening of anti-IBD agents,due to their unique biological advantages.Based on the latest research progress using zebrafish in the field of IBD,this review systematically introduces the intestinal development characteristics,tissue structure,intestinal immunity,IBD model,and the application of drug screening in zebrafish,to demonstrate the value of zebrafish in the study of IBD.

A 62-year-old female patient underwent medical thoracoscopic pleural biopsy for undiagnosed pleural effusion. Preoperative vital signs in the patient were stable, with no cardiovascular, cerebrovascular or neurological underlying diseases. During the procedure, midazolam 2 mg (0.045 mg/kg) and fentanyl 150 μg (3.3 μg/kg) were administered by intravenous injection for sedation and analgesia. Two minutes later, the patient developed respiratory depression, and her oxygen saturation decreased to 42%. Immediate jaw thrust maneuver followed by bag-valve-mask ventilation was initiated, and the spontaneous respiration resumed and oxygen saturation recovered (>90%) after 2 minutes, allowing successful biopsy of a pleural nodule. The patient was fully conscious in the immediate postoperative period, with normal ability of communication and mobility. However, at 6 hours postoperatively, she developed anterograde and retrograde amnesia, disorientation, sensation disorders, nausea, and retching. Cranial magnetic resonance imaging revealed no significant abnormalities. These symptoms were considered to be related to transient higher cortical dysfunction induced by the sedative and analgesic agents. Given supportive treatments including fluid administration, the symptoms were gradually improved at 8 hours postoperatively, and resolved completely by 11 hours postoperatively.

Objective To determine the effect of thrombus aspiration combined with intracoronary injection of recombinant human TNK tissue type plasminogen activator(rhTNK-tPA)on micro-circulation and cardiac function during primary PCI in elderly patients with acute myocardial in-farction(AMI).Methods A retrospective study was conducted on 90 elderly patients with STEMI undergoing primary PCI in Tianjin Third Central Hospital from January 2021 to October 2023.According to their treatment strategies,they were divided into simple suction group(n=46)and combination group(n=44).The suction group received a suction catheter for thrombus aspiration within the coronary artery,while the combined group got a suction catheter for thrombus aspira-tion within the infarct related blood vessels,and then received a local injection of rhTNK-tPA into the lesion through the suction catheter.Their general data,proportion of ST segment resolution(STR)≥70％at 90 min after surgery,postoperative TIMI blood flow grade,postoperative TIMI myocardial perfusion grade(TMPG),corrected TIMI frame count(CTFC)and cardiac ultrasound indicators as well as the incidence of adverse cardiac events during hospitalization were compared between the two groups.Results Larger proportions of postoperative STR ≥70％,postoperative TIMI blood flow grade 3 and TMPG grade 3,and lower CTFC were observed in the combination group than the suction group(P＜0.05).In 1 week after surgery,the simple suction group had lower left ventricular ejection fraction[LVEF,(52.5±6.2)％vs(58.3±6.4)％,P＜0.05],but larger left ventricular diameter(LVD,44.1±3.9 mm vs 51.9±2.5 mm,P＜0.05)than the com-bined group.The incidence of MACE during hospitalization was obviously lower in the combined group than the suction group(20.5％vs 37.0％,P＜0.05).Conclusion Combined intracoronary injection of rhTNK-tPA based on thrombotic aspiration can effectively reduce the coronary thrombus burden,improve myocardial microcirculation perfusion,reduce the incidence of MACE during hospitalization,and not increase the risk of bleeding in elderly STEMI patients.

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment(TME),which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma(HNSCC)patients.This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology.The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing(scRNA-seq)profiles and validated through bulk transcriptomes.Serine-glycine-one-carbon(SGOC)metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients.A 4-SGOC gene prognostic signature,constructed by LASSO-COX regression analysis,demonstrated good predictive performance for overall survival and therapeutic responses.Patients in the low-risk group exhibited greater infiltration of exhausted CD8+T cells,and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy.Conversely,high-risk patients exhibited characteristics of cold tumors,with enhanced IMPDH1-mediated purine biosynthesis,resulting in poor responses to current therapies.IMPDH1 emerged as a potential therapeutic metabolic target.Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress.Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment(TME),which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma(HNSCC)patients.This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology.The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing(scRNA-seq)profiles and validated through bulk transcriptomes.Serine-glycine-one-carbon(SGOC)metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients.A 4-SGOC gene prognostic signature,constructed by LASSO-COX regression analysis,demonstrated good predictive performance for overall survival and therapeutic responses.Patients in the low-risk group exhibited greater infiltration of exhausted CD8+T cells,and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy.Conversely,high-risk patients exhibited characteristics of cold tumors,with enhanced IMPDH1-mediated purine biosynthesis,resulting in poor responses to current therapies.IMPDH1 emerged as a potential therapeutic metabolic target.Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress.Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.
Humans ; Male ; Animals ; Mice ; Semen/metabolism* ; Dyneins/metabolism* ; Cilia/metabolism* ; Mutation ; Ciliary Motility Disorders/genetics*

Primary ciliary dyskinesia (PCD) is a hereditary disease characterized by airway mucociliary clearance dysfunction. The estimated prevalence of PCD is 1꞉10 000 to 1꞉20 000. The main respiratory manifestations in children are cough, expectoration, chronic rhinitis, sinusitis, and chronic otitis media, while the most common symptoms in adults are chronic sinusitis, bronchiectasis, and infertility. About 50% of patients with certain PCD-related gene variants are combined with situs inversus, and the incidence of congenital heart disease is also high. The pathogenesis behind PCD is that gene variants cause structural or functional disorders of respiratory cilia and motile cilia of other organs, leading to a series of heterogeneous clinical manifestations, which makes it difficult to identify and diagnose PCD. Combining different disease screening tools and understanding the relationship between genotypes and phenotypes may facilitate early diagnosis and treatment for PCD.
Chronic Disease ; Cilia/pathology* ; Humans ; Kartagener Syndrome/genetics* ; Phenotype ; Sinusitis

Objective To summarize CT and MRI features of hyaline vascular type localized Castleman disease(LCD)and analyze the causes of misdiagnosis,to improve the preoperative diagnosis rate.Methods The clinical and imaging data of 7 patients with hyaline vascular type LCD confirmed by operation and pathology were analyzed retrospectively.Results (1)6 cases were misdiagnosed before operation,1 case was misdiagnosed as pancreatic neuroendocrine tumor,1 case as thymoma,1 case as neurogenic tumor,1 case as pheochromocytoma, 1 case as clear cell renal cell carcinoma and 1 case as small mesenteric stromal tumor.(2)1 case was located in the right neck,1 case in the anterior superior mediastinum,1 case in the neck of the pancreas,1 case in the upper part of the left kidney,2 cases in the retroperitoneum and 1 case in the lower abdomen.(3)3 cases were scaned by dynamic enhanced MRI,3 cases were scaned by dynamic enhanced CT, and 1 case was checked by plain CT and enhanced MRI.CT and MRI showed that 7 cases had a round or elliptical soft tissue mass, and 4 cases with well defined margin,3 cases were not clear in edge,2 cases with spot or strip calcification on CT images,4 cases had slightly longer T1 and longer T2 signal,4 cases were restricted of diffusion and had higher signal on DWI.All the lesions were enhanced in arterial phase,and went on in the delayed phase.There were 5 cases with distorted vascular shadow in the middle and/or around of the mass, 3 cases with strips,spoke-like low-density areas or low-signal areas,and some lesions were filled in delayed phase.Conclusion CT and MRI features of hyaline vascular type LCD have certain characteristics such as rich blood supply,enhancement in persistent,tortuosity of peripheral vascular,with some short strip calcification and high signal on DWI,which may be helpful for preoperative diagnosis.