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1.
Chinese Pharmacological Bulletin ; (12): 90-98, 2024.
Article in Chinese | WPRIM | ID: wpr-1013596

ABSTRACT

Aim To investigate the effect of ellagic acid (EA) on cognitive function in APP/PS 1 double- transgenic mice, and to explore the regulatory mechanism of ellagic acid on the level of oxidative stress in the hippocampus of double-transgenic mice based on the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3 (PI3K/AKT/GSK-3 β) signaling pathway. Methods Thirty-two SPF-grade 6-month-old APP/PS 1 double transgenic mice were randomly divided into four groups, namely, APP/PS 1 group, APP/PS1 + EA group, APP/PS1 + LY294002 group, APP/PS 1 + EA + LY294002 group, with eight mice in each group, and eight SPF-grade C57BL/6J wild type mice ( Wild type) were selected as the blank control group. The APP/PS 1 + EA group was given 50 mg · kg

2.
Chinese Journal of Pathology ; (12): 22-28, 2024.
Article in Chinese | WPRIM | ID: wpr-1012419

ABSTRACT

Objective: To investigate the clinicopathological characteristics, diagnosis and differential diagnosis of intravascular large B-cell lymphoma (IVLBCL) and its collision tumors. Methods: Five cases of IVLBCL were collected, including 2 cases of collision tumors, and 1 case complicated with liver cirrhosis. The morphology and immunophenotype were analyzed. The related literature was reviewed. Results: There were 2 females and 3 males, aged from 53 to 73 years, with a median age of 65 years. The tumors were located in the lower extremities, right cerebellar hemisphere, left kidney, bilateral nasal cavity, and liver, respectively. Cases 2 and 3 were incidentally found in meningioma and renal cell carcinoma tissues, respectively. Case 5 had a background of liver cirrhosis. Morphologically, atypical large lymphoid cells were located in small blood vessels and capillary lumen, with little cytoplasm, hyperchromasia, prominent nucleoli, and obvious mitotic figures. Immunohistochemically, the IVLBCL tumor cells expressed CD20 and PAX5; 2 cases were CD5 positive. One of the 5 cases was GCB phenotype, and 4 cases were non-GCB phenotype. All cases expressed C-MYC (positive rate was 10%-40%). PD-L1 was positive in 4 cases (positive rate was 60%-90%). Ki-67 proliferation index was 70%-90%. CKpan, CD3, TDT, and CD34 were negative. In case 2, meningioma cells were positive for PR, EMA, and vimentin, but negative for CKpan and PD-L1. In case 3, renal carcinoma cells were positive for CKpan, PAX8, EMA, vimentin, CAⅨ and CD10, while PD-L1 was negative. No EBER expression (by in situ hybridization) or C-MYC gene translocation (FISH, break-apart probe) was detected in any of the 5 cases. Three patients were followed up, and all died within 1-13 months. Conclusions: IVLBCL is a highly aggressive lymphoma, with occult clinical manifestations and poor prognosis. Collision tumors of IVLBCL are extremely rare. A better understanding of IVLBCL would help pathologists avoid misdiagnoses.


Subject(s)
Male , Female , Humans , Aged , B7-H1 Antigen , Vimentin , Meningioma , Lymphoma, Large B-Cell, Diffuse/pathology , Carcinoma, Renal Cell , Kidney Neoplasms/pathology , Meningeal Neoplasms , Liver Cirrhosis
3.
Protein & Cell ; (12): 36-51, 2024.
Article in English | WPRIM | ID: wpr-1010778

ABSTRACT

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.


Subject(s)
Humans , Vascular Endothelial Growth Factor A/metabolism , Endothelial Cells/metabolism , Transcription Factors/metabolism , Gene Expression Regulation , Hypoxia/metabolism , Cell Hypoxia/physiology
4.
Journal of Zhejiang University. Science. B ; (12): 1-22, 2024.
Article in English | WPRIM | ID: wpr-1010594

ABSTRACT

Cardiovascular diseases (CVDs) are a leading factor driving mortality worldwide. Iron, an essential trace mineral, is important in numerous biological processes, and its role in CVDs has raised broad discussion for decades. Iron-mediated cell death, namely ferroptosis, has attracted much attention due to its critical role in cardiomyocyte damage and CVDs. Furthermore, ferritinophagy is the upstream mechanism that induces ferroptosis, and is closely related to CVDs. This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy, and the regulatory pathways and molecular targets involved in ferritinophagy, and to determine their roles in CVDs. Furthermore, we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs. Collectively, this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.


Subject(s)
Humans , Cardiovascular Diseases , Ferroptosis , Iron , Trace Elements
5.
Chinese Pharmacological Bulletin ; (12): 560-568, 2023.
Article in Chinese | WPRIM | ID: wpr-1013835

ABSTRACT

Aim To predict the targets of Modified Danggui Shaoyao San ( MDSS) in the treatment of chronic atrophic gastritis ( CAG) based on network pharmacology and vertify the results based on experim-ention. Methods TCMSP, SWISS TARGETS, GENE CARDS and OMIM databases were used to screen the therapeutic targets of MDSS for CAG. STRING database and Cytoscape software were used to construct the protein interaction network and screen the core targets. Metascape database was used for GO analysis and KEGG enrichment pathways. And molecular docking was used for target validation. CAG rat model was pre¬pared by N-methyl-N'-nitroso-N-nitroguanidine free drink combined with sodium salicylate gastric lavage. The pathology of rat gastric mucosa was observed by hematoxylin-eosin staining,and the ultrastructure of ep¬ithelial cells was observed by transmission electron mi-croscopy. The serum IL-6 and IL-10 content was detected by enzyme-linked immunosorbent assay, and the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in rats was detected by qPCR and Western blot. Results MDSS acted on 189 targets, mainly involved in response to oxidative stress and apoptotic signaling pathway. KEGG analysis related to pathways in cancer and JAK-STAT signaling pathway. The experimental results showed that the MDSS could improve the degree of atrophy of gastric mucosa in CAG rats and improve the status of epithelial cells, down-regulate the serum IL-6 content of CAG rats, up-regulate the IL-10 content, and reduce the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in gastric mucosa with statistical significance. Conclusions MDSS treats CAG through multiple active ingredients, targets, and pathways, the mechanism of which may be related to the inhibition of the JAK2/STAT3 signaling pathway.

6.
Chinese Pharmacological Bulletin ; (12): 1613-1617, 2023.
Article in Chinese | WPRIM | ID: wpr-1013701

ABSTRACT

Tyrosine kinase inhibitors (TKIs) are a class of molecular targeted drugs that inhibit the activation of downstream signaling pathways by inhibiting oncogene-related receptor tyrosine kinases to exert anti-cancer effects. TKIs are superior to traditional chemotherapeutics in terms of selectivity, effectiveness and safety, and are widely used in the treatment of cancer. However, TKIs-induced liver injury is one of the difficult problems in its clinical application. In this article, relevant literatures from domestic and abroad are reviewed and the research progress in the classification, clinical application of TKIs and the mechanism of TKIs-induced liver injury are summarized. This review intends to provide a reference for further elucidating the mechanism of TKIs-induced liver injury, and seeking effective prevention and treatment methods.

7.
Chinese Journal of Pathology ; (12): 832-837, 2023.
Article in Chinese | WPRIM | ID: wpr-1012316

ABSTRACT

Objective: To investigate the expression of MSI1 and HER2 in mammary Paget's disease, and the correlation between the expression levels of MSI1 and HER2 and the clinicopathologic characteristics and prognosis of the patients. Methods: Clinical data and paraffin-embedded specimens of 34 pairs of mammary Paget's disease and underlying breast cancer were collected at the Department of Pathology, Affiliated Lianyungang Oriental Hospital of Xuzhou Medical University from March 2011 to December 2019. Immunohistochemistry was used to detect the expression of MSI1 and HER2 in mammary Paget's disease and the accompanying breast cancer, and to analyze the correlation between the expression levels of MSI1 and HER2 and their clinicopathologic features, as well as their influence on prognosis. Results: In mammary Paget's disease, the positive rate of MSI1 was 91.2% (31/34) and the positive rate of HER2 was 88.2% (30/34); the expression of MSI1 and HER2 was positively correlated (P=0.001, r=0.530). The expression of MSI1 was positively correlated with menopausal status (r=0.372, P=0.030) and lymph node metastasis (r=0.450, P=0.008). HER2 expression was positively correlated with menopausal status (r=0.436, P=0.010), and negatively correlated with ER expression (r=-0.365, P=0.034). The co-expression of MSI1 and HER2 was positively correlated with age (r=0.347, P=0.044) and menopausal status (r=0.496, P=0.003), and negatively correlated with ER expression (r=-0.461, P=0.006). Conclusions: MSI1 and HER2 are highly expressed in mammary Paget's disease and their expression levels are positively correlated. The correlation analysis between clinicopathological features and prognosis suggests that both of them may be involved in the occurrence and development of mammary Paget's disease and are potential therapeutic targets for mammary Paget's disease.


Subject(s)
Humans , Female , Paget's Disease, Mammary/pathology , Breast Neoplasms/pathology , Prognosis , Lymphatic Metastasis , Nerve Tissue Proteins/metabolism , RNA-Binding Proteins
8.
Chinese Journal of Hematology ; (12): 825-831, 2023.
Article in Chinese | WPRIM | ID: wpr-1012239

ABSTRACT

Objective: To explore the clinical characteristics and treatment of COVID-19 infection in patients with relapsed/refractory B-cell non-Hodgkin lymphoma before and after receiving chimeric antigen receptor T-cell therapy, and study the influencing factors of severe COVID-19 infection in these patients. Methods: The data of 59 patients with relapsed/refractory B-cell non-Hodgkin lymphoma who received chimeric antigen receptor T-cell therapy at the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology and Department of Hematology, the Second Affiliated Hospital, College of Medicine, Zhejiang University between December 2017 and February 2023, and who were infected with novel coronavirus between December 2022 and February 2023 were retrospectively studied. Patients were divided into light, medium, severe, and critical groups, and the differences between the groups were analyzed using the chi-square test. A univariate logistic regression model was used to evaluate the contribution of each variable and its relationship with severe infection. The chi-square and Fisher's exact tests were used to analyze the differences between the B-cell aplasia and B-cell recovery (BCR) groups. Results: Of the 59 pre- and post-infusion infections, 39 (66.1%) led to mild COVID-19, 9 (15.3%) resulted in moderate COVID-19, 10 (16.9%) resulted in severe COVID-19, and 1 (1.7%) led to critical COVID-19. Moroever, age greater than 55 years, having received autologous hematopoietic stem cell transplantation, progressive disease status, and B-cell aplasia at the time of diagnosis of COVID-19 infection are factors affecting severe infection. Patients with B-cell aplasia had a more severe infection with COVID-19 (P<0.001), a longer duration (P=0.015), a longer antiviral therapy course (P<0.001), and a higher hospitalization rate (P<0.001) than the BCR group. Conclusion: Active prevention and treatment of COVID-19 infection remains a crucial issue requiring urgent attention in managing patients with relapsed/refractory B-cell non-Hodgkin lymphoma treated with chimeric antigen receptor T-cell therapy.


Subject(s)
Humans , Adult , Middle Aged , Receptors, Chimeric Antigen , Retrospective Studies , COVID-19/therapy , SARS-CoV-2 , Lymphoma, B-Cell/therapy , Cell- and Tissue-Based Therapy
9.
Chinese Journal of Hematology ; (12): 820-824, 2023.
Article in Chinese | WPRIM | ID: wpr-1012238

ABSTRACT

Objective: This study systematically explore the efficacy and safety of fourth-generation chimeric antigen receptor T-cells (CAR-T), which express interleukin 7 (IL7) and chemokine C-C motif ligand 19 (CCL19) and target CD19, in relapsed or refractory large B-cell lymphoma. Methods: Our center applied autologous 7×19 CAR-T combined with tirelizumab to treat 11 patients with relapsed or refractory large B-cell lymphoma. The efficacy and adverse effects were explored. Results: All 11 enrolled patients completed autologous 7×19 CAR-T preparation and infusion. Nine patients completed the scheduled six sessions of tirolizumab treatment, one completed four sessions, and one completed one session. Furthermore, five cases (45.5%) achieved complete remission, and three cases (27.3%) achieved partial remission with an objective remission rate of 72.7%. Two cases were evaluated for disease progression, and one died two months after reinfusion because of uncontrollable disease. The median follow-up time was 31 (2-34) months, with a median overall survival not achieved and a median progression-free survival of 28 (1-34) months. Two patients with partial remission achieved complete remission at the 9th and 12th months of follow-up. Therefore, the best complete remission rate was 63.6%. Cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome were controllable, and no immune-related adverse reactions occurred. Conclusion: Autologous 7×19 CAR-T combined with tirelizumab for treating relapsed or refractory large B-cell lymphoma achieved good efficacy with controllable adverse reactions.


Subject(s)
Humans , Antibodies, Monoclonal/therapeutic use , Antigens, CD19 , Chemokine CCL19 , Immunotherapy, Adoptive , Interleukin-7 , Lymphoma, Large B-Cell, Diffuse/therapy , Programmed Cell Death 1 Receptor , Receptors, Chimeric Antigen
10.
Chinese Journal of Hematology ; (12): 813-819, 2023.
Article in Chinese | WPRIM | ID: wpr-1012237

ABSTRACT

Objective: To further elucidate the clinical efficacy and safety of a combination regimen based on the BTK inhibitor zebutanil bridging CD19 Chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) . Methods: Twenty-one patients with high-risk r/r DLBCL were treated with a zanubrutinib-based regimen bridging CAR-T between June 2020 and June 2023 at the Department of Hematology, Tongji Hospital, Tongji University and the Second Affiliated Hospital of Zhejiang University, and the efficacy and safety were retrospectively analyzed. Results: All 21 patients were enrolled, and the median age was 57 years (range: 38-76). Fourteen patients (66.7%) had an eastern cooperative oncology group performance status score (ECOG score) of ≥2. Eighteen patients (85.7%) had an international prognostic index (IPI) score of ≥3. Three patients (14.3%) had an IPI score of 2 but had extranodal infiltration. Fourteen patients (66.7%) had double-expression of DLBCL and seven (33.3%) had TP53 mutations. With a median follow-up of 24.8 (95% CI 17.0-31.6) months, the objective response rate was 81.0%, and 11 patients (52.4%) achieved complete remission. The median progression-free survival (PFS) was 12.8 months, and the median overall survival (OS) was not reached. The 1-year PFS rate was 52.4% (95% CI 29.8% -74.3%), and the 1-year OS rate was 80.1% (95% CI 58.1% -94.6%). Moreover, 18 patients (85.7%) had grade 1-2 cytokine-release syndrome, and two patients (9.5%) had grade 1 immune effector cell-associated neurotoxicity syndrome. Conclusion: Zanubrutinib-based combination bridging regimen of CAR-T therapy for r/r DLBCL has high efficacy and demonstrated a good safety profile.


Subject(s)
Humans , Middle Aged , Receptors, Chimeric Antigen/therapeutic use , Retrospective Studies , Immunotherapy, Adoptive/adverse effects , Lymphoma, Large B-Cell, Diffuse/drug therapy , Cell- and Tissue-Based Therapy , Antigens, CD19/adverse effects
11.
Protein & Cell ; (12): 888-907, 2023.
Article in English | WPRIM | ID: wpr-1010764

ABSTRACT

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.


Subject(s)
Animals , Male , Testis , Sertoli Cells/metabolism , Transcriptome , Spermatogenesis/genetics , Primates , Aging/genetics , Stem Cells
12.
Journal of Zhejiang University. Science. B ; (12): 711-722, 2023.
Article in English | WPRIM | ID: wpr-1010565

ABSTRACT

Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry, and the next-generation sequencing (NGS) to identify the pathological and molecular characteristics of CL. In the first case, the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body. An excisional biopsy of the skin lesions showed T-cell lymphoma. At the same time, the staging bone marrow (BM) biopsy revealed a diffuse large B-cell lymphoma (DLBCL). After R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapies, the patient produced a good response with substantial dissipation of the rashes and relief of skin. The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma (FL) after core needle biopsy of lymph nodes, BM biopsy, BM aspiration, and flow cytometry. Following R-CHOP and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone) therapies, they achieved complete remission unconfirmed (CRu) and complete remission (CR). However, one or two years later, they suffered a relapse of lymphadenopathy. The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL). NGS findings identified DNA methyltransferase 3a (DNMT3a), isocitrate dehydrogenase 2 (IDH2), Ras homolog gene family, member A (RHOA), splicing factor 3B subunit 1 (SF3B1), and tumor protein p53 (TP53) mutations. After immunochemotherapy, these patients achieved CRu and CR again. Nevertheless, they suffered a second relapse of T-cell lymphoma. Finally, they died due to progression of disease. We found that the occurrence of CL is associated with Epstein-Barr virus infection and DNMT3a, IDH2, and TP53 mutations, and the prognosis of the disease is closely related to the T-cell lymphoma components.


Subject(s)
Humans , Rituximab/therapeutic use , Vincristine/therapeutic use , Prednisone/therapeutic use , Epstein-Barr Virus Infections/drug therapy , Herpesvirus 4, Human , Neoplasm Recurrence, Local , Lymphoma, T-Cell/drug therapy , Cyclophosphamide/therapeutic use , Lymphoma, Large B-Cell, Diffuse/pathology , Doxorubicin/therapeutic use , Lymphadenopathy/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
13.
Chinese Journal of Rehabilitation Theory and Practice ; (12): 182-192, 2023.
Article in Chinese | WPRIM | ID: wpr-965031

ABSTRACT

ObjectiveTo analyze the content and psychological measurement indicators of the commonly used motor function assessment tools for children and adolescents, based on the theory and method of International Classification of Function, Disability and Health-Children and Youth Version (ICF-CY). MethodsBased on the ICF-CY classification framework and coding system, four commonly used functional evaluation tools for children and adolescents were selected, and their motor function measurement methods and psychological measurement indicators were analyzed by applying ICF coding rules and matching principles. ResultsFinally, nine English articles and two Chinese articles were included, from four countries including South Korea, Spain, China and Brazil. They were mainly published in the journals of clinical medicine, neuroscience, public health, rehabilitation science and other fields from 2011 to 2021. The age of the subjects was 0 to 16 years old involving 987 subjects; the health condition included spastic cerebral palsy, neurodevelopmental disorder, etc. Among the eleven articles included, six articles used Gross Motor Function Measure (GMFM-88), two articles used Fine Motor Function Measure Scale (FMFM), two articles used Peabody Developmental Motor Scales Second Edition (PDMS-2), and two articles used Pediatric Evaluation of Disability Inventory-Functional Skills Scale (PEDI-FSS), and three articles used Pediatric Evaluation of Disability Inventory (PEDI). The measurement methods were objective evaluation, subjective evaluation, and subjective observation, etc. The number of measurements was two to six. The measurement indicators of motor function mainly involved two levels. The first was the physical activity level, including gross movement, fine movement and motor control ability. The second was the functional level of activities, mainly including activities of daily living and functional independence. ConclusionBased on ICF-CY, the evaluation of children's motor function and activity and participation was mainly divided into two levels. At the body function level, the main evaluation indicators included b730, b760, b770, etc. At the level of activities and participation, the main evaluation indicators were d410, d440, d445, etc. GMFM-88 focuses on the evaluation of children's body movement and activity functions, such as sitting, standing, lying, walking and running, mainly involving b760, d410, d455, etc. FMFM focused on autonomous movement, motor motivation and motor coordination, and was mainly used to assess the functional status of upper limbs of children with cerebral palsy aged 0 to 3 years, mainly involving b760, d155, d440, etc. PDMS-2 payed more attention to evaluating the overall motor development level and motor function status of children and adolescents, mainly involving b750, b760, d415, etc. PEDI-FSS move partition focused on children's actual motor function performance in activities of daily living, and evaluated the application and practicability of children's motor function in activities of daily living, mainly involving b760, d410, d450, etc. In terms of measurement methods, the measurement of motor function mainly included objective evaluation and subjective evaluation; the measurement of activity function mainly included objective evaluation and subjective observation. These assessment tools have established norms varies with different age groups according to the movement development. Evaluators need accept professional training before using the above assessment tools to improve the reliability, validity and adaptability of the assessment.

14.
Chinese Journal of Biotechnology ; (12): 4123-4134, 2023.
Article in Chinese | WPRIM | ID: wpr-1008016

ABSTRACT

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.

15.
Chinese Medical Journal ; (24): 2621-2631, 2023.
Article in English | WPRIM | ID: wpr-1007549

ABSTRACT

BACKGROUND@#The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication.@*METHODS@#Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)-messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard.@*RESULTS@#Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A . In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression ( P  <0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs.@*CONCLUSIONS@#This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents.


Subject(s)
Humans , Female , Genomics , Carcinogenesis , Carcinoma , Breast Neoplasms , Cell Transformation, Neoplastic , Nucleotides , Tumor Microenvironment
16.
Chinese Journal of Radiological Health ; (6): 661-667, 2023.
Article in Chinese | WPRIM | ID: wpr-1006324

ABSTRACT

Objective To address the absence of matrix specified for the determination of intrinsic uniformity in the current standard, and to investigate the effect of source distances on intrinsic spatial linearity, the intrinsic uniformity and intrinsic spatial linearity of 16 probes in eight SPECT devices were measured and analyzed with different matrices and source distances, in order to determine the optimal measurement conditions. Methods According to the standard Specification for Testing of Quality Control in Gamma Cameras and Single Photon Emission Computed Tomograph (SPECT) (WS 523—2019), the intrinsic uniformity was measured using 64 × 64 and 256 × 256 matrices and the intrinsic spatial linearity was measured using of 1.7 and 3 m source distances. Results When intrinsic uniformity was measured with the 64 × 64 matrix, more than 50% of the probes showed lower values. When intrinsic spatial linearity was measured with the 3 m source distance, more probes showed lower values. Conclusion The 64 × 64 matrix is recommended for the determination of intrinsic uniformity and a source distance of >5 FOV is recommended for the measurement of intrinsic spatial linearity.

17.
Journal of Modern Urology ; (12): 323-328, 2023.
Article in Chinese | WPRIM | ID: wpr-1006083

ABSTRACT

【Objective】 To investigate the efficacy of negative pressure suction and topical testosterone cream in the treatment of simple micropenis in school-aged obese children and the effects on blood lipids and serum sex hormones. 【Methods】 A total of 79 children aged 7 to 14 (10.50±1.62) years treated and followed up during Nov.2020 and Jul.2022 were involved. The patients were randomly enrolled in the negative pressure suction group (n=39) and the topical testosterone cream group (n=40). The negative pressure suction group was treated with negative pressure suction for 30 min/time, 1 time/day, for 30 d. The topical testosterone cream group was treated with topical testosterone cream applied to the scrotum of the penis 2 times/day for 30d. The transverse and longitudinal diameter of the glans, penile flaccidity, retraction length, serum sex hormones and blood lipids were measured before and after treatment. 【Results】 In both groups, penile flaccidity, retracted length and transverse and longitudinal diameter of the glans were significantly greater at 30 days of treatment and 2 months of follow-up than those before treatment (P0.025). In the topical testosterone cream group, at 30 days of treatment, there were significant differences in serum total cholesterol (CHOL), apolipoprotein B (Apo B), apolipoprotein A1 (Apo A1), high-density lipoprotein (HDL), low-density lipoprotein (LDL), sex hormone binding protein (SBG), estradiol (E2) and testosterone (TES) compared to those before treatment; at 2 months of follow-up, the differences in Apo A1, HDL, TES and DHS were still significant (P<0.025). 【Conclusion】 Both topical testosterone cream and negative pressure suction have significant efficacy in the treatment of micropenis in school-aged obese children, while topical testosterone cream has some side effects and retraction may occur after treatment. Negative pressure suction is safe and easy to operate, without side effects and retraction, and can be promoted for the treatment of micropenis in obese children.

18.
Journal of Modern Urology ; (12): 692-695, 2023.
Article in Chinese | WPRIM | ID: wpr-1006012

ABSTRACT

【Objective】 To investigate the risk factors and predictive effectiveness of prostate imaging reporting and data system (PI-RADS) score for patients with clinically significant prostate cancer (CsPCa) whose PI-RADS score was 3, so as to provide evidence for the diagnosis and treatment. 【Methods】 The clinical and multi-parameter magnetic resonance imaging (mpMRI) data of 153 CsPCa patients treated during Jan.2017 and Dec.2021 whose PI-RADS score was 3 were retrospectively analyzed. With PI-RADS score of 3 as the independent risk factor for CsPCa, the other relevant independent risk factors in predicting CsPCa were evaluated. 【Results】 Univariate and multivariate analyses showed that prostate-specific antigen (PSA) density and apparent dispersion coefficient (ADC) were independent risk factors for the diagnosis of CsPCa (P<0.05). Analysis of receiver operating characteristic (ROC) curve showed that combined PSA density and ADC were more effective than PSA density and ADC alone (P<0.05). 【Conclusion】 The combination of PSA density and ADC can guide clinicians to identify high-risk CsPCa patients from patients with PI-RADS score of 3 points.

19.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 14-21, 2023.
Article in Chinese | WPRIM | ID: wpr-1005495

ABSTRACT

【Objective】 To investigate the correlation of monocytes and high-density lipoprotein cholesterol ratio(MHR) and albumin with the severity of coronary artery lesions in patients with unstable angina pectoris. 【Methods】 We enrolled 342 patients with unstable angina pectoris. According to the Gensini score of their coronary angiography results, they were divided into Gensini≤ 20 group, 20<Gensini ≤40 group, and Gensini >40 group. The differences in biochemical indicators between the groups were compared, and the correlation between the different indicators and the Gensini score was analyzed. According to the MHR quartile grouping, there were differences between the comparison groups. LDL-C was divided into subgroups and then subjected to multifactor Logistic regression analysis. 【Results】 MHR differed significantly among low, moderate and high grade lesions (P<0.05). Subgroup analysis showed that in low LDL-C group, Gensini score was positively correlated with MHR(P<0.05), while in high LDL-C group, Gensini score was negatively correlated with albumin(P<0.05). Multivariate Logistic regression analysis showed that the MHR level of patients with high Gensini score was 102.375 times higher than that of patients with low Gensini score(P<0.05). In the group with high LDL-C, the serum albumin level in the group with low Gensini score was 1.431 times that in the group with high Gensini score and 1.218 times that in the group with moderate Gensini score(all P<0.05). 【Conclusion】 In patients with unstable angina pectoris, especially when LDL-C levels are not high, both high MHR and low serum albumin are independent risk factors for the severity of coronary artery disease.

20.
Chinese Journal of Blood Transfusion ; (12): 428-431, 2023.
Article in Chinese | WPRIM | ID: wpr-1004840

ABSTRACT

【Objective】 To study the effect of perioperative allogeneic blood transfusion on patients with oral squamous cell carcinoma (OSCC) after first-stage free flap transplantation. 【Methods】 A total of 306 OSCC patients who accepted primary repair and reconstruction using free flap admitted to our affiliation from January 2010 to January 2019 were selected as the research objects and retrospectively analyzed. According to their clinical data, they were divided into three groups: no transfusion group (n=98), 1-2 U transfusion group (n=131) and 3 + U transfusion group (n=77), respectively. The incidence of complications including flap infection, blood circulation disorder and hematoma in the three groups were compared. The five-year survival rate of the three groups was calculated by Kaplan-Meier analysis, and the relative risk of death was analyzed by Cox regression. 【Results】 There was no statistically significant difference among the three groups of patients (P>0.05) regarding such baseline data as embracing gender, age, primary location, degree of differentiation, adjuvant radiotherapy and chemotherapy. The complication rate of patients with 3 + U transfusion (25.97%) was significantly higher than that of no transfusion (6.12%) and 1-2 U transfusion (10.86%) (P<0.05); and the five-year survival rate of patients with 3 + U transfusion (51.95%) was significantly lower than that of no transfusion (69.38%) and 1-2 U transfusion (62.60%) (P<0.05). The results of univariate analysis showed that age, adjuvant radiotherapy, degree of tissue differentiation, collateral infiltration, vascular invasion and blood transfusion were all factors influencing the quality of prognosis after repair and reconstruction of first-stage free flap transplantation treating OSCC (P<0.05). The results of multivariate analysis showed that adjuvant chemoradiotherapy was an independent protective factor for the prognosis and survival quality of postoperative OSCC patients (P<0.01); the degree of differentiation, vascular invasion and blood transfusion were independent risk factors for the prognosis and survival quality of postoperative OSCC patients (P<0.05). 【Conclusion】 Perioperative allogeneic transfusion in OSCC patients can increase the risk of postoperative complications and directly affect their prognostic quality. It can be regarded as an important risk factor for OSCC patients.

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