Purpose: Breast cancer (BC) is a predominant malignancy globally, surpassing lung cancer in terms of diagnostic frequency, with an escalating incidence rate in recent decades.Recent studies have investigated the role of protein kinase C zeta (PRKCZ) in diverse cellular processes in cancer biology. In this study, we evaluated the association between PRKCZ and deleterious outcomes in BC and elucidated the mechanisms underlying its expression in breast carcinoma. Methods: The correlation between PRKCZ and survival rates of patients with BC was investigated using The Cancer Genome Atlas database. The methylation status of the PRKCZ promoter was analyzed using the UALCAN database. Furthermore, we investigated the mechanisms underlying PRKCZ inactivation in BC by treatment with transferase inhibitors, methylation-specific polymerase chain reaction (PCR) analysis, western blotting, and luciferase reporter gene assays. The degree of methylation and expression levels of PRKCZ, as regulated by DNA methyltransferase 1 (DNMT1), were quantified using quantitative PCR and western blotting. Results: Our analysis revealed that decreased expression of PRKCZ in BC was significantly correlated with poor clinical prognosis. Furthermore, we observed that hypermethylation of the PRKCZ promoter contributed to its reduced expression in BC. Notably, DNMT1 has been identified as a critical regulator of PRKCZ methylation. Conclusion Our findings elucidate the tumor-suppressive function of PRKCZ and provide insights into the molecular mechanisms underlying its downregulation in BC.

Purpose: Breast cancer (BC) is a predominant malignancy globally, surpassing lung cancer in terms of diagnostic frequency, with an escalating incidence rate in recent decades.Recent studies have investigated the role of protein kinase C zeta (PRKCZ) in diverse cellular processes in cancer biology. In this study, we evaluated the association between PRKCZ and deleterious outcomes in BC and elucidated the mechanisms underlying its expression in breast carcinoma. Methods: The correlation between PRKCZ and survival rates of patients with BC was investigated using The Cancer Genome Atlas database. The methylation status of the PRKCZ promoter was analyzed using the UALCAN database. Furthermore, we investigated the mechanisms underlying PRKCZ inactivation in BC by treatment with transferase inhibitors, methylation-specific polymerase chain reaction (PCR) analysis, western blotting, and luciferase reporter gene assays. The degree of methylation and expression levels of PRKCZ, as regulated by DNA methyltransferase 1 (DNMT1), were quantified using quantitative PCR and western blotting. Results: Our analysis revealed that decreased expression of PRKCZ in BC was significantly correlated with poor clinical prognosis. Furthermore, we observed that hypermethylation of the PRKCZ promoter contributed to its reduced expression in BC. Notably, DNMT1 has been identified as a critical regulator of PRKCZ methylation. Conclusion Our findings elucidate the tumor-suppressive function of PRKCZ and provide insights into the molecular mechanisms underlying its downregulation in BC.

Purpose: Breast cancer (BC) is a predominant malignancy globally, surpassing lung cancer in terms of diagnostic frequency, with an escalating incidence rate in recent decades.Recent studies have investigated the role of protein kinase C zeta (PRKCZ) in diverse cellular processes in cancer biology. In this study, we evaluated the association between PRKCZ and deleterious outcomes in BC and elucidated the mechanisms underlying its expression in breast carcinoma. Methods: The correlation between PRKCZ and survival rates of patients with BC was investigated using The Cancer Genome Atlas database. The methylation status of the PRKCZ promoter was analyzed using the UALCAN database. Furthermore, we investigated the mechanisms underlying PRKCZ inactivation in BC by treatment with transferase inhibitors, methylation-specific polymerase chain reaction (PCR) analysis, western blotting, and luciferase reporter gene assays. The degree of methylation and expression levels of PRKCZ, as regulated by DNA methyltransferase 1 (DNMT1), were quantified using quantitative PCR and western blotting. Results: Our analysis revealed that decreased expression of PRKCZ in BC was significantly correlated with poor clinical prognosis. Furthermore, we observed that hypermethylation of the PRKCZ promoter contributed to its reduced expression in BC. Notably, DNMT1 has been identified as a critical regulator of PRKCZ methylation. Conclusion Our findings elucidate the tumor-suppressive function of PRKCZ and provide insights into the molecular mechanisms underlying its downregulation in BC.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Objective To explore imaging manifestations of crossed ectopic fused kidney.Methods Data of 12 patients with crossed ectopic fused kidney were retrospectively analyzed,and the imaging manifestations of crossed ectopic fused kidney were observed.Results L type crossed ectopic fused kidney was detected in 5 cases,while inferior ectopic type(Ii type),S-shaped type and lump type(O type)ectopic fused kidney was found each in 2 cases,respectively,and doughnut or disc type(C-C type)ectopic fused kidney was noticed in 1 case.The ectopic fused kidney presented with empty one side renal cavity,while the morphology and position of the contralateral kidney were generally normal in all 12 cases,which crossed the midline and fused with the contralateral in situ kidney,including right to left crossed ectopic fusion in 8 cases and left to right crossed ectopic fusion in 4 cases.The ureters of the crossing kidney went across the midline,opened into the bladder trigone on the contralateral side in 11 cases or prostate in 1 case.Combined reproductive system abnormalities were found in 3 cases,including unicornous uterus,bicornuate uterus and cryptorchidism each in 1 case.Two cases were found complicated with abnormal inferior vena cava,including 1 case of both side inferior vena cava and 1 case of left inferior vena cava.Conclusion The imaging manifestations of crossed ectopic fused kidney had characteristics.Complete displaying of reveal fused kidney,ureteral course and opening was helpful to accurate diagnosis and classification of crossed ectopic fused kidney.

Objective To retrieve,extract,evaluate,and integrate the relevant evidence of postoperative pulmonary rehabilitation management in patients with lung cancer complicated with chronic obstructive pulmonary disease,so as to provide an evidence-based basis for improving the quality of postoperative pulmonary rehabilitation.Methods Relevant literature on postoperative pulmonary rehabilitation of lung cancer complicated with chronic obstructive pulmonary disease were searched by computer from clinical decisions,guideline websites,professional association websites,and comprehensive databases.The types of the literature included clinical decisions,guidelines,expert consensuses,evidence summaries,systematic reviews,meta-analyses,and randomized controlled trials.The retrieval time limit was from the establishment of the database to September 2023.Results A total of 19 articles were included,including 4 clinical decisions,3 guidelines,6 expert consensuses,1 evidence summary,3 systematic reviews,and 2 randomized controlled trials.Through reading,extraction and classification,23 pieces of best evidence were finally formed,including multidisciplinary cooperation,evaluation,pulmonary rehabilitation strategies and health education.Conclusion This study summarizes the best evidence for postoperative lung rehabilitation management in patients with lung cancer and chronic obstructive pulmonary disease.Clinical medical staff can implement practical evidence for postoperative lung rehabilitation based on actual situations,and promote the transformation of evidence-based knowledge into practice.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled

Objective:To study the protective effects and mechanisms of melatonin (MTn) on lipopolysaccharide (LPS) and hypoxic-ischemic(HI) induced white matter damage (WMD) in neonatal rats.Methods:Seventy-two 3-day-old newborn Sprague-Dawley (SD) rats were randomly assigned into sham operation group (the sham group), model group (the HI group) and MTn intervention group (the HI+MTn group) ( n=24 for each group). For the sham group, only dissection of the right common carotid artery was performed without ligation. Animal models of WMD were established using LPS pretreatment and HI method in both the HI group and HI+MTn group. The HI+MTn group received MTn intraperitoneal injection (15 mg/kg, 1 h before LPS injection and then once daily). The HI group and the sham group received equal volume of normal saline containing 1% ethanol intraperitoneal injection. The rats were sacrificed on d7 of experiment and periventricular white matter (PVWM) was collected for hematoxylin-eosin (HE) and TUNEL staining to determine WMD and apoptosis. The distribution and morphology of microglial cells in the PVWM were studied using IBA1 immunofluorescence staining. Reactive oxygen species (ROS) kit was used to detect ROS. The expression of nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes, interleukin (IL)-1β, IL-18 and mitochondrial autophagy markers (pink1 and parkin) were determined using real-time quantitative PCR. Results:Compared with the sham group, the HI group showed WMD, cell degeneration and necrosis,increased cell apoptosis and increased expressions of NLRP3 inflammasomes and downstream inflammatory factors (IL-1β and IL-18) in PVWM. Compared with the HI group,the HI+MTn group showed reduced WMD, cell apoptosis, microglia infiltration and inflammatory factors expression. MTn increased pink1 and parkin expression and reduced ROS production in PVWM.Conclusions:MTn reduces ROS production by enhancing mitochondrial autophagy and inhibits NLRP3 inflammasomes hyperactivation to alleviate endotoxin- and HI-induced WMD in neonatal rats.

Objective:To evaluate the efficacy of esketamine combined with fascia iliaca compartment-subarachnoid block in optimizing anesthesia in elderly patients undergoing hip fracture surgery.Methods:Sixty-two American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ elderly patients of either sex, aged 60-85 yr, with body mass index of 18.5-30.0 kg/m 2, were divided into 2 groups ( n=31 each) using a random number table method: fascia iliaca compartment-subarachnoid block group (FS group) and esketamine combined with fascia iliaca compartment-subarachnoid block group (ES group). In FS group, patients underwent ultrasound-guided fascia iliaca compartment block at 30 min before the operation of subarachnoid anesthesia on the surgical side. In ES group, esketamine 0.25 mg/kg was intravenously administered at 5 min before skin incision based on the fascia iliaca compartment-subarachnoid block. Patient-controlled intravenous analgesia was used for postoperative analgesia, and tramadol 1 mg/kg was intravenously given for rescue analgesia when numerical rating scale score > 4. The pressing times of patient-controlled analgesic pump, the number of rescue analgesia and consumption of tramadol were recorded within 48 h after operation. The occurrence of postoperative adverse reactions (respiratory depression, nausea and vomiting, dizziness, drowsiness, pruritus, illusion, nightmares) was recorded. Results:Compared with FS group, the consumption of postoperative tramadol was significantly decreased, and the pressing times of patient-controlled analgesic pump and the number of rescue analgesia were reduced in ES group ( P<0.05). There were no significant differences in the incidence of postoperative adverse reactions between the two groups ( P>0.05). Conclusions:Combination of esketamine with fascia iliaca compartment-subarachnoid block for hip fracture surgery can raise postoperative analgesia and optimize clinical management strategies in elderly patients.

Neonatal hypoxic-ischemic encephalopathy often causes long-term adverse effect on neurological system or even death in near-term or full-term infants, but no effective treatment is available currently. Studies have shown that xenon can reduce brain injury caused by hypoxia-ischemia and is promising in clinical practice. The possible mechanisms include antagonism to glutamic acid receptors, anti-apoptosis, promotion of cell repair and xenon preconditioning. This article reviews the mechanism and research progress on neuroprotection effect of xenon in the treatment of neonatal hypoxic-ischemic encephalopathy.