Objective To explore the relationship between dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and clinical pathological features of invasive breast cancer and lymphovascular invasion(LVI).Methods Imaging and clinical pathological data were retrospectively collected from 508 patients with invasive breast cancer who underwent breast DCE-MRI at the First Medical Center of Chinese PLA General Hospital from January 2019 to August 2021.Patients were divided into the LVI-positive(LVI+)group(n=79)and LVI-negative(LVI-)group(n=429)based on postoperative pathological results.Univariate and multivariate logistic regression analyses were used to identify risk factors for LVI.Results Compared with LVI-group,LVI+group had a higher proportion of patients aged<45 years(44.3%vs.27.0%,P=0.002),non-mass-like enhancement(NME)(31.7%vs.17.7%,P=0.004),Ki-67 expression rate(40.0%vs.30.0%,P<0.001),high Ki-67 expression(94.9%vs.78.1%,P=0.001),Luminal B subtype(76.0%vs.60.1%,P=0.008),and positive axillary lymph nodes rate(72.2%vs.31.5%,P<0.001),while the proportion of Luminal A subtype was lower(2.5%vs.21.5%,P<0.001).Univariate and multivariate logistic regression analyses showed that age≥45 years(OR=0.468,95%CI 0.280-0.783,P=0.004)was an independent protective factor for LVI,while NME(OR=1.987,95%CI 1.126-3.444,P=0.016)was an independent risk factor.Compared with Luminal A subtype,patients with Luminal B subtype(OR=10.482,95%CI 3.164-64.923,P=0.001),HER-2 overexpression subtype(OR=11.571,95%CI 2.755-79.341,P=0.003)and triple-negative subtypes(OR=8.433,95%CI 1.985-57.908,P=0.009)had a higher risk of LVI.Conclusions Age≥45 years is an independent protective factor for LVI,while NME is an independent risk factor.Among molecular subtypes,patients with Luminal B,HER-2 overexpression and triple-negative subtypes have a higher risk of LVI compared with the Luminal A subtype.

Objective:To investigate the clinical manifestation, therapy, and prognosis of Susac syndrome and enhance the understanding of this disease.Methods:A case summary was made.The clinical data of two siblings with Susac syndrome treated at Children′s Medical Center, Peking University First Hospital in January 2024 were summarized.Reported cases of pediatric Susac syndrome were reviewed.Results:The onset of the disease in the two siblings was at the age of 3.00 and 6.75 years, with recurrent headaches, tinnitus, hearing loss and encephalopathy symptoms.Cranial magnetic resonance imaging showed multiple cerebral microbleeding and microinfarction lesions, " snowball like" in the corpus callosum and diffuse white matter edema in the brain.Audiometry revealed sensorineural hearing loss.In one case, ophthalmic fluorescein angiography revealed ischemic changes due to branch retinal artery occlusions.No pathogenic variants were detected in gene testing.This child was diagnosed with Susac syndrome, and the symptoms were improved after treatment with Corticosteroids and Rituximab.No relapse was observed during the 9-month follow-up.A total of 20 pediatric cases of Susac syndrome were retrieved, including 18 reported previously and 2 cases from this study.There were 2 boys and 18 girls, with the age of onset ranging from 2.5 to 17.0 years.The common initial symptoms included headache (19 cases), vertigo and tinnitus or hearing loss (9 cases), and vision impairment or visual field defect (4 cases). The symptoms were improved after immunotherapy.Conclusions:With a low incidence, Susac syndrome is rare in children and difficult to diagnose.There may be a genetic predisposition in such disease.Early diagnosis and immunotherapy can low the relapse and improve the prognosis.

Objective:To investigate the clinical manifestation, therapy, and prognosis of Susac syndrome and enhance the understanding of this disease.Methods:A case summary was made.The clinical data of two siblings with Susac syndrome treated at Children′s Medical Center, Peking University First Hospital in January 2024 were summarized.Reported cases of pediatric Susac syndrome were reviewed.Results:The onset of the disease in the two siblings was at the age of 3.00 and 6.75 years, with recurrent headaches, tinnitus, hearing loss and encephalopathy symptoms.Cranial magnetic resonance imaging showed multiple cerebral microbleeding and microinfarction lesions, " snowball like" in the corpus callosum and diffuse white matter edema in the brain.Audiometry revealed sensorineural hearing loss.In one case, ophthalmic fluorescein angiography revealed ischemic changes due to branch retinal artery occlusions.No pathogenic variants were detected in gene testing.This child was diagnosed with Susac syndrome, and the symptoms were improved after treatment with Corticosteroids and Rituximab.No relapse was observed during the 9-month follow-up.A total of 20 pediatric cases of Susac syndrome were retrieved, including 18 reported previously and 2 cases from this study.There were 2 boys and 18 girls, with the age of onset ranging from 2.5 to 17.0 years.The common initial symptoms included headache (19 cases), vertigo and tinnitus or hearing loss (9 cases), and vision impairment or visual field defect (4 cases). The symptoms were improved after immunotherapy.Conclusions:With a low incidence, Susac syndrome is rare in children and difficult to diagnose.There may be a genetic predisposition in such disease.Early diagnosis and immunotherapy can low the relapse and improve the prognosis.

Purpose To explore the clinicopathological features and molecular characteristics of primary CD5+diffuse large B cell lymphoma(DLBCL).Methods Immunohisto-chemistry and next-generation sequencing(NGS)were used to compare the pathological features,immunophenotypes,and mo-lecular characteristics between primary CD5+DLBCL and CD5-DLBCL,and to analyze their relationship with prognosis and clinical characteristics of patients.Results Among 311 DLBCL patients,there were 46 cases(14.7％)of CD5+DLBCL.There were no statistically significant differences in patient gen-der,clinical staging,international prognostic index between CD5+DLBCL and CD5-DLBCL,and between CD5+DLBCL with and without MYD88 L265P mutation(P＞0.05).Immuno-phenotypically,the overexpression of BCL2(69.5％vs 49.4％,P=0.003)and the co-expression of BCL2 and C-MYC(26％vs 14％,P=0.04)were higher in the CD5+DLBCL group than those in the CD5-DLBCL group;the expression of C-MYC(53％vs 20％),BCL6(93.3％vs 61.3％),Ki67(93.3％vs 64.5％),and co-expression(46.7％vs 20.8％)were higher in the CD5+with MYD88 L265P mutation group than those in the CD5+without MYD88 L265P mutation group(P＜0.05).Survival analysis showed that the disease progres-sion-free survival time of patients in the CD5+DLBCL group tended to be shorter than that of patients in the CD5-DLBCL group(P=0.09).Furthermore,the disease progression-free survival time of patients in the CD5+without MYD88 L265P mutation group was significantly longer than that of patients in the CD5+with MYD88 L265P mutation group(P=0.04).NGS detection found differences in the distribution of accompan-ying mutated genes between CD5+DLBCL and CD5-DLBCL groups.ConclusionCD5 expression and CD5+with MYD88 L265P mutation may be potential indicators of poor prognosis in DLBCL patients.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To investigate the efficacy and safety of bendamustine combined with gemcitabine, vinorelbine，glucocorticoids (BeGEV)±X regimen in treatment of patients with relapsed/refractory non-Hodgkin lymphoma. METHODS: A total of 18 relapsed/ refractory non-Hodgkin lymphoma patients at the age of 18 years or older hospitalized in the First People's Hospital of Changzhou from March 2020 to March 2021 were selected. They received two or more cycles of BeGEV±X regimen. X could be anti-CD20 monoclonal antibody, PD-1-blocking antibodies, lenalidomide, BTK inhibitor, Bcl-2 inhibitor and so on according to patients' disease feature. The clinical efficacy and adverse effects were observed. RESULTS: In total, 18 patients completed two or more cycles of BeGEV±X regimen, including 14 with diffuse large B-cell lymphoma, one with low-grade follicular lymphoma, one with follicular lymphoma grade 3b, one with angioimmunoblastic T-cell lymphoma and one with peripheral T-cell lymphoma, not otherwise specified. 11 patients were male. The median age of the patients was 64 years old. 17 patients had modified Ann Arbor stage Ⅲ/Ⅳ disease. 13 patients had high- intermediate risk or high risk IPI score, while 15 patients had high-intermediate high risk or high risk NCCN-IPI score. 14 cases had extranodal sites of disease. And 6 cases had bulky disease. 12 patients experienced refractory disease, while 8 patients had received 3 line or more prior treatment. After two or three cycles of chemotherapy, the complete response rate was 6/18, the partial response rate was 3/18, and the objective response rate was 9/18. From the beginning of salvage chemotherapy to the end of follow-up, the median progression-free survival time was 130 days, and the median overall survival was 152 days. The most common grade 3 to 4 adverse events were hematologic toxicities, infection and febrile neutropenia. CONCLUSION BeGEV±X is an effective salvage regimen in treatment of patients with relapsed/refractory non-Hodgkin lymphoma, while adverse events such as hematologic toxicities and infection should be closely monitored.
Humans ; Male ; Middle Aged ; Adolescent ; Female ; Lymphoma, Follicular/drug therapy*

Objective: To analyze the change trend of underground dust concentration, the incidence and survival status of pneumoconiosis patients, and provide reference for improving the working environment of dust-exposed workers and the prevention and treatment of pneumoconiosis patients in the future. Methods: In February 2020, a retrospective investigation was conducted on the dust data of underground mining operations in a steel enterprise in Jiangsu Province from 1991 to 2019, and the case data of patients diagnosed with pneumoconiosis from 1956 to 2019 were collected. The time trends of the number of pneumoconiosis patients and dust concentration, the stage of pneumoconiosis and survival status of patients were analyzed. Results: From 1956 to 2019, a total of 241 patients with pneumoconiosis were diagnosed in the steel enterprise. From 1991 to 2019, the annual average dust concentration in the mine showed a downward trend as a whole. Compared with the transportation platform (14.28%, 1447/10132) , the average dust concentration exceeding rate of the mining platform (43.68%, 8415/19263) was significantly higher (χ(2)=2674.84, P<0.01) . The average age of pneumoconiosis patients was (73.54±10.42) years old, and the average working age of dust exposure was (21.41±8.68) years, of which 85 cases (35.27%) survived and 156 cases (64.73%) died. The main type of pneumoconiosis was silicosis (90.46%, 218/241) , and the main stage of pneumoconiosis was the stage I (96.68%, 233/241) ; The higher the stage of pneumoconiosis, the younger the diagnosis age (P<0.01) . The average survival time of patients was (27.264±1.982) years, and the median survival time was 28 years. The cumulative survival rates of patients with pneumoconiosis in different diagnosis time periods were significantly different (χ(2)=35.57, P<0.01) . Conclusion: The improved dust-proof measures have a significant effect on reducing the concentration of underground dust. We need to focus on the dust control of underground mining platforms and the treatment of patients with stage Ⅲ pneumoconiosis.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Child ; Adolescent ; Young Adult ; Adult ; Incidence ; Coal Mining ; Steel ; Retrospective Studies ; Pneumoconiosis/diagnosis* ; Dust ; Occupational Exposure/adverse effects*

OBJECTIVE: KRAS gene is one of the most common mutations of proto-oncogenes in human tumors, G12V is one of the most common mutation types for KRAS. It's challenging to chemically acquire the targeted drug for this mutation. Recent studies reported that this mutation peptides can form a neoepitope for T cell recognition. Our study aims to clone the T cell receptor (TCR) which specifically recognizes the neoepitope for KRAS G12V mutation and constructs TCR engineered T cells (TCR-T), and to investigate if TCR-Ts have strong antitumor response ability. METHODS: In this study, tumor infiltrating lymphocytes were obtained from one colorectal cancer patient carrying KRAS G12V mutation. Tumor-reactive TCR was obtained by single-cell RT-5' rapid-amplification of cDNA ends PCR analysis and introduced into peripheral blood lymphocytes to generate TCR-Ts. RESULTS: We obtained a high-affinity TCR sequence that specifically recognized the HLA-A^*11:01-restricted KRAS G12V_8-16 epitope: KVA11-01. KVA11-01 TCR-T could significantly kill various tumor cells such as PANC-1, SW480 and HeLa (overexpressing HLA-A^*11:01 and KRAS G12V), and secreting high levels of interferon-γ (IFN-γ). Non-specific killing experiments suggested KVA11-01 specifically recognized tumor cells expressing both mutant KRAS G12V and HLA-A^*11:01. In vivo assay, tumor inhibition experiments demonstrated that infusion of approximately 1E7 KVA11-01 TCR-T could significantly inhibit the growth of subcuta-neously transplanted tumors of PANC-1 and HeLa (overexpressing HLA-A^*11:01 and KRAS G12V) cells in nude mice. No destruction of the morphologies of the liver, spleen and brain were observed. We also found that KVA11-01 TCR-T could significantly infiltrate into tumor tissue and had a better homing ability. CONCLUSION KVA11-01 TCR-T cells can effectively target a variety of malignant tumor cells carrying KRAS G12V mutation through in vitro and in vivo assay. KVA11-01 TCR-T cells have excellent biological activity, high specificity of target antigen and homing ability into solid tumor tissue. KVA11-01 TCR-T is expected to be an effective treatment for patients with KRAS G12V mutant solid malignancies.
Animals ; DNA, Complementary ; Epitopes ; HLA-A Antigens ; Humans ; Interferon-gamma ; Mice ; Mice, Nude ; Mutation ; Neoplasms ; Proto-Oncogene Proteins p21(ras)/genetics* ; Receptors, Antigen, T-Cell/genetics*