The metastasis and recurrence of tumors is a common cause of refractory and death in patients. The disseminated tumor cells from the primary tumor can infiltrate distal organs and enter a dormant state to evade treatment. Under the particular circumstances, some of the dormant cells are revived and multiply to create metastatic lesions. Although tumor dormancy-activation plays a significant role in mediating the metastasis and recurrence of tumors, the exact mechanism underlying tumor dormancy and recurrence is still unclear. Recent studies have shown that the metastatic niche of the distal organs may provide a special environment for dormancy and activation of disseminated tumor cells. This review focuses on the latest mechanism of the metastatic niche and tumor dormancy, including interactions between tumor cells and niche, and immune regulation within the niche, aiming to provide novel perspectives for cancer treatment and prognosis assessment.

Membrane-bound organelles and membraneless organelles (MLOs) coordinate various biological processes within eukaryotic cells. Among these, stress granules (SGs) are significant cytoplasmic MLOs that form in response to cellular stress, exhibiting liquid-like properties alongside stable substructures. SGs interact with diverse organelles, thereby influencing cellular pathways that are critical in both health and disease contexts. This review discusses the interplay between SGs and organelles and explores the methodologies employed to analyze interactions between SGs and other MLOs. Furthermore, it highlights the pivotal roles SGs play in regulating cellular responses and the pathogenesis of amyotrophic lateral sclerosis. Gaining insights into these interactions is essential for deciphering the mechanisms underlying both physiological processes and pathological conditions.
Humans ; Stress Granules/pathology* ; Organelles/metabolism* ; Amyotrophic Lateral Sclerosis/pathology* ; Animals ; Stress, Physiological ; Cytoplasmic Granules/metabolism*

Chimeric antigen receptor T (CAR-T) cells have reshaped the treatment landscape of hematological malignancies, offering a potentially curative option for patients. Despite these major milestones in the field of immuno-oncology, growing experience with CAR-T cells has also highlighted several limitations of this strategy. The production process of CAR-T cells is complex, time-consuming, and costly, thus leading to poor drug accessibility. The potential carcinogenic risk of viral transfection systems remains a matter of controversy. Treatment-related side effects, such as cytokine release syndrome, can be life-threatening. And the biggest challenge is the inadequate efficacy related to poor infiltration and retention of CAR-T cells in tumor tissues and impaired T cell activation caused by the immunosuppressive tumor microenvironment (TME). Innovative strategies are urgently needed to address these problems, and nanomedicine offers good solutions to these challenges. In this review, we provide a comprehensive summary of recent advancements in the application of nanomaterials to enhance CAR-T cell therapy. We examine the role of innovative nanoparticle-based delivery systems in the production of CAR-T cells, with a particular focus on polymeric delivery systems and lipid nanoparticles (LNPs). Furthermore, we explore various strategies for delivering immune stimulators, which significantly enhance the efficacy of CAR-T cells by modulating T cell viability and functionality or by reprogramming the immunosuppressive TME. In addition, we discuss several novel therapeutic approaches aimed at mitigating the adverse effects associated with CAR-T therapies. Finally, we offer an integrated perspective on the future challenges and opportunities facing CAR-T therapies.
Humans ; Nanomedicine/methods* ; Receptors, Chimeric Antigen/metabolism* ; Immunotherapy, Adoptive/methods* ; T-Lymphocytes/immunology* ; Nanoparticles/chemistry* ; Animals

Background and aims:Clinical data regarding patients with chronic hepatitis B(CHB)after Omicron BA.5 infection are currently limited.This study aimed to assess the clinical characteristics of patients with CHB and Omicron BA.5 infection in South China.Methods:This retrospective study was conducted from January to March 2023 in a cohort of 485 healthy individuals and 553 patients with CHB.Clinical features,encompassing COVID-19-related symptoms,levels of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)antibodies,vaccination status,liver functions,and virological markers of hepatitis B virus(HBV)infection were measured.Results:COVID-19-related symptom patterns were similar in both groups,except for fever,which was notably less prevalent(85.4％vs.90.4％,P=0.047)among patients with CHB who experienced a significantly shorter duration of fever(median 2.2(25th-75th percentile,1.0-3.0)days vs.2.3(1.0-3.0)days,P=0.048)and a shorter time for symptom relief(9.2(5.0-14.0)vs.11.1(5.0-14.0)days,P=0.015).The levels of SARS-CoV-2 antibodies were comparable between the two groups but increased after booster vaccinations.In patients with CHB,globulin(GLB)and hepatitis B envelope antibody levels were significantly increased after Omicron BA.5 infection,regardless of nucleos(t)ide analog regimens comparing entecavir(ETV)with tenofovir(TFV).Patients with CHB treated with TFV had significantly higher levels of SARS-CoV-2 antibodies than those treated with ETV(1065.1(346.9-1188.5)COI vs.765.5(24.5-1119.1)COI,P=0.025).Conclusions:No significant exacerbation of COVID-19 symptoms was observed in conjunction with the efficacy of COVID-19 booster vaccinations.There were no notable alterations in liver functions except for GLB.HBV reactivation,as evidenced by increased HBV DNA,was observed among patients with CHB after Omicron BA.5 infection.These changes were not affected by ETV versus TFV administration;however,TFV resulted in a significant increase in SARS-CoV-2 antibody levels.Further studies are required to improve care and therapeutics for patients with CHB who contracted COVID-19.

The metastasis and recurrence of tumors is a common cause of refractory and death in patients. The disseminated tumor cells from the primary tumor can infiltrate distal organs and enter a dormant state to evade treatment. Under the particular circumstances, some of the dormant cells are revived and multiply to create metastatic lesions. Although tumor dormancy-activation plays a significant role in mediating the metastasis and recurrence of tumors, the exact mechanism underlying tumor dormancy and recurrence is still unclear. Recent studies have shown that the metastatic niche of the distal organs may provide a special environment for dormancy and activation of disseminated tumor cells. This review focuses on the latest mechanism of the metastatic niche and tumor dormancy, including interactions between tumor cells and niche, and immune regulation within the niche, aiming to provide novel perspectives for cancer treatment and prognosis assessment.

Objective:To investigate the efficacy and safety of Rituximab (RTX) in the treatment of children with frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS) and to analyze the factors influencing the efficacy.Methods:Case series study.The clinical data of children with FRNS/SDNS who received B-cell-guided RTX (single dose: 375 mg/m 2, maximum dose: 500 mg, one additional dose when peripheral blood CD19 + B lymphocytes ≥0.01) in the First Affiliated Hospital of Zhengzhou University from September 2019 to March 2022 were retrospectively collected.The frequency of relapse and cumulative dose of glucocorticoids before and after RTX treatment were compared.The Kaplan-Meier method was used to analyze relapse-free survival rate and FRNS/SDNS-free survival rate after RTX treatment.The influencing factors of relapse were analyzed using the Cox proportional hazards regression model. Results:Totally 47 children were enrolled, including 35 males and 12 females; the age of first application of RTX was 10.2 (6.9, 13.0) years; 33 children had used one type of immunosuppressant before, and 14 children had used two or more types of immunosuppressant before; the dose of RTX treatment was 3.0 (2.0, 3.0). The frequency of relapse[0(0, 0.55) times/year vs.1.62 (1.09, 2.40) times/year] and cumulative dose of glucocorticoids[0.12 (0.05, 0.21) mg/(kg·d) vs.0.40 (0.20, 0.56) mg/(kg·d)] after RTX treatment significantly decreased compared with previous immunosuppressive treatment ( Z=-5.56, -5.54, all P<0.001). The relapse-free survival rates at 6, 12, 18 and 24 months after treatment were 80.9%, 72.3%, 68.1% and 68.1%, respectively, and the FRNS/SDNS-free survival rates were 93.6%, 89.4%, 89.4% and 89.4%, respectively.Univariate Cox regression analysis showed that the high frequency of relapse during previous immunosuppressive therapy was a risk factor for relapse after RTX treatment ( P<0.05). Of the 14 children who relapsed, 6 occurred in children whose CD19 + B lymphocytes<0.01, and the frequency of relapse after RTX treatment was significantly higher than those whose CD19 + B lymphocytes≥0.01 ( Z=-2.84, P=0.005). No severe adverse reactions occurred during RTX treatment and follow-up. Conclusions:The B-cell-guided RTX is effective and safe in the treatment of FRNS/SDNS in children.The high frequency of relapse during previous immunosuppressive therapy is a risk factor for relapse after RTX treatment, and relapse in the state of B lymphocyte depletion predicts poor outcomes of RTX treatment.

Background Pesticide exposure may impact the reproductive health of women undergoing assisted reproductive technology (ART). However, data on pesticide exposure levels in women undergoing ART in China are scarce, and current research on influencing factors is limited. Objective To evaluate the preconceptional pesticide exposure levels and identify potential determinants among women undergoing ART. Methods This study was designed as a cross-sectional survey and recruited 508 women undergoing ART from July 2017 to December 2018 at the fertility clinic of the International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Gas chromatography/liquid chromatography-tandem mass spectrometry was used to determine the metabolite concentrations of organophosphate pesticides (OPs), pyrethroid pesticides (PYRs), and neonicotinoid pesticides (NEOs) in urine. The sum of molar concentrations of the three pesticide classes (∑₂OPs, ∑₂PYRs, and ∑₂NEOs) were calculated. A questionnaire was used to collect demographic characteristics, dietary habits, and behavioral information. Multiple linear regression was employed to analyze the associations of demographic characteristics, dietary habits, and behavioral variables with the concentrations of pesticide metabolites in urine among the participants. Results The median creatinine-adjusted concentrations of ∑₂OPs, ∑₂PYRs, and ∑₂NEOs in this study were 419.77, 2.95, and 20.36 nmol·g⁻¹, respectively. The multiple linear regression results showed that the urinary concentration of ∑₂OPs was 42.88% higher in the participants with daily vegetable intake than in those who consumed vegetables ≤3 d per week (P<0.05), and the urinary concentration of ∑₂PYRs was 37.24% higher in the participants with daily fruit intake than in those who consumed fruits ≤3 d per week (P<0.01). Similarly, the urinary concentrations of ∑₂NEOs were 24.51% and 29.30% higher in the participants who consumed fruits daily and 4-6 d per week, respectively, than in those who consumed fruits ≤3 d per week (P<0.05). Besides, we also found that the urinary concentration of ∑₂PYRs was negatively correlated with body mass index (BMI) in the participants (P<0.05). Furthermore, the urinary concentration of ∑₂NEOs was not only positively correlated with age (P<0.05), but also significantly associated with pet ownership and infertility causes among the participants. Specifically, the participants who continued to own pets after conception had a 30.11% higher urinary concentration of ∑₂NEOs than those who never owned pets (P<0.05), and the participants with infertility due to female factors had a 24.10% lower urinary concentration of ∑₂NEOs than those who received ART treatment for infertility caused by male factors (P<0.05). Conclusion The women undergoing ART in Shanghai are widely exposed to pesticides. Age, BMI, frequency of vegetable and fruit intake, pet ownership, and infertility causes may be related to the pesticide exposure levels in this population. However, more human data are needed to confirm these findings.

Refractory acute T-lymphoblastic leukemia (T-ALL), which is characterized by a low sensitivity to conventional induction therapy and poor prognosis, poses significant challenges during treatment. This study reported a case of refractory T-ALL patient with mutations in the JAK1, JAK3, and STAT5B genes from Nanjing University’s Gulou Hospital. Following an unsuccessful course of standard VDLP regimen chemotherapy, the treatment was modified to include ruxolitinib in combination with venetoclax and azacitidine. Subsequent to this therapy, the patient achieved bone marrow minimal residual disease (MRD) negativity. Notably, pleural effusion and mediastinal mass significantly improved the post-chest cavity infusion of dexamethasone combined with etoposide at the same stage. The patient also underwent allogeneic hematopoietic stem cell transplantation upon achieving bone marrow remission and was followed up until January 2024. Ruxolitinib combined with venetoclax and azacytidine has shown promising efficacy and safety in treating refractory T-ALL harboring the JAK1, JAK3, and STAT5B mutations, providing a novel therapeutic approach for such patients.

Objective To explore the chromosome,molecular genetic abnormalities and survival prognosis of adults with acute leukemia(non-M3 type).Methods A total of 148 adult patients with acute leukemia who visited the Department of Hematology of Fuyang People's Hospital from December 2019 to December 2022 were selected as the research subjects.The chromosome karyotype and molecular genetic characteristics of the patients were detected and analyzed by using chromosome banding analysis techniques(R-banding)and fluorescence in situ hybridization.The general information,laboratory examina-tions and prognosis of the patients were collected from the medical records and questionnaires of the subjects.The Kaplan-Meier method was used to draw the survival curve.The survival analysis was tested by the Log-Rank method.Results Among the 148 adult patients with acute leukemia,62 developed acute lymphoblastic leukemia(ALL),with the majority of subtypes being B,and 86 developed acute myeloid leukemia(AML),with the majority of subtypes being M2 and M5.Bone marrow chromosome examination was successfully performed in 141 patients,and there was no significant difference in the proportion of abnormal bone marrow chromosome karyotypes between AML patients and ALL patients(x2=1.864,P＞0.05).A total of 143 patients completed fusion gene examination,and the results showed that 28 of 81 AML patients were fusion gene positive,including 8 cases(9.87％)of mixed lineage leukemia-rearranged(MLL-R)fusion gene,and 20 of 62 ALL patients were fusion gene positive,including 6 cases(9.68％)of MLL-R fusion gene.The incidence of hepatosplenomegaly was significantly higher in patients with positive MLL-R than in patients with negative MLL-R(x2=3.645,P＜0.05),and the incidence of elevated peripheral leukocyte count(≥100 x 109 L-1)was also higher in patients with positive MLL-R than in patients with negative MLL-R(x2=7.051,P＜0.05).The incidence of abnormal bone marrow chromosome karyotype was higher in patients with positive MLL-R than in patients with negative MLL-R(x2=13.961,P＜0.05).There was no significant difference in leukemia typing,age,gender,platelet count and hemoglobin level between patients with positive MLL-R and those with negative MLL-R(P＞0.05).In the ALL group,there was no significant difference in remission rate,relapse rate and mortality rate between MLL-R positive and MLL-R negative patients(P＞0.05);in the AML group,there was no significant difference in remission rate,relapse rate and mortality rate between MLL-R positive and MLL-R negative patients(P＞0.05).There was no significant difference in mortality rate between leukemia patients who received chemotherapy and bone marrow stem cell transplantation(P＞0.05).The 1-year event free survival(EFS)rates of ALL and AML patients were(41.90±3.20)％and(38.20±2.20)％,respectively,and there was no significant difference in the 1-year EFS rate between the ALL and AML patients(x2=0.512,P＞0.05).The 1-year overall survival(OS)rates of ALL and AML patients were(60.50±4.20)％and(58.20±4.60)％,respectively,and there was no significant difference in the 1-year OS rate between the ALL and AML patients(x2=0.175,P＞0.05).The 1-year EFS rates of MLL-R positive and MLL-R negative patients were(34.60±2.70)％and(36.20±3.10)％,respectively,and there was no significant difference in the 1-year EFS rate between the MLL-R positive and MLL-R negative patients(x2=0.579,P＞0.05).The 1-year OS rates of MLL-R positive and MLL-R negative patients were(37.30±4.20)％and(56.60±5.20)％,respectively,and there was a significant difference in the 1-year OS rate between the MLL-R positive and MLL-R negative patients(x2=4.092,P＜0.05).Conclusion There is no significant difference in abnormal chromosome karyotype between AML and ALL patients.The fusion gene MLL-R can be found in both AML and ALL patients.Although MLL-R positive patients are more likely to have hepatosplenomegaly,abnormal chromosome karyotype and elevated leukocyte count,the efficacy shows no significant difference between MLL-R positive patients and negative patients.The current treatment for AML and ALL patients is mainly chemotherapy.Although MLL-R negative patients have better 1-year OS rates than MLL-R positive patients,there is no significant difference in the 1-year EFS rate between MLL-R positive and MLL-R negative patients.

Objective:To develop a Cognitive Assessment Scale for Spinal Cord Injury (SCI) Rehabilitation and conduct reliability and validity tests in community-dwelling patients with SCI.Methods:Based on expectation value theory, social cognition theory, and goal setting theory, a Cognitive Assessment Scale for SCI Rehabilitation was developed through literature review, group discussions, patient trials, and expert verification. From February to December 2021, convenience sampling was used to select 231 community-dwelling patients with SCI as research subjects, including 67 community-dwelling patients with SCI who participated in rehabilitation training at Shanghai Sunshine Rehabilitation Center and 164 patients with SCI in the "Hope Home" WeChat group of Shanghai Sunshine Rehabilitation Center. Research subjects were surveyed using the Cognitive Assessment Scale for SCI Rehabilitation (patient version), 9-item depression scale of Patient Health Questionnaire, 7-item Generalized Anxiety Disorder Scale, EuroQol 5 Dimension-Visual Analogue Scale (EQ-VAS), General Self-Efficacy Scale, and general information questionnaire. SPSS 16.0 software and Amos 21.0 software were used for correlation analysis and reliability and validity testing.Results:The Cognitive Assessment Scale for SCI Rehabilitation (patient version) included two primary dimensions, eight secondary dimensions, and 24 items. The trial showed good results among patients with SCI and their caregivers, and experts generally agreed. Exploratory factor analysis found that the scale were divided into recognition dimension and understanding dimension. Cronbach's α coefficient of the scale was 0.98, the correlation coefficient between each item and its corresponding dimension was 0.75 to 0.88, and our results indicated good test-retest reliability. Correlation analysis showed that patient anxiety and depression scores were negatively correlated with rehabilitation cognitive scores ( P<0.05), and self-efficacy, quality of life were positively correlated with rehabilitation cognitive scores ( P<0.05) . Conclusions:The Cognitive Assessment Scale for SCI Rehabilitation is scientific and feasible, with good reliability and validity, and can be used to evaluate the rehabilitation cognition of community-dwelling patients with SCI.