Background During urbanization, the passenger load on urban public transport systems continues to increase, exposing bus drivers to a high risk of musculoskeletal disorders (MSDs). This occupational health issue may also potentially compromise public transport safety. Objective To investigate the prevalence of MSDs among bus drivers in a first-tier city and to explore associated influencing factors. Methods A self-administered questionnaire survey was conducted from December 2024 to March 2025 among 1300 bus drivers in a bus company. Data were collected on general demographic information, occupational activities, and MSDs indicators. A total of 1268 valid questionnaires were returned, yielding a response rate of 97.5%. Descriptive statistics were used to analyze the distribution characteristics of MSDs. Pearson χ² tests were employed to examine the association between MSDs prevalence and individual/occupational characteristics. Logistic regression was performed to identify the influencing factors of MSDs. Results The survey revealed that the prevalence of MSDs among the bus drivers was 28.5%, with the highest prevalence in the 41–50 years age group (30.5%). The conditions primarily affected the cervical spine (60.5%) and lumbar spine (61.9%), with some cases involving multiple sites. The logistic regression model indicated that the following factors were associated with a higher risk of MSDs: frequent smoking (OR=1.477), poor or moderate self-reported health status (OR=4.422), 11–20 years of service (OR=1.749), daily cumulative driving time ≥361 min (OR=1.616), frequent whole-body fatigue during driving (OR=2.077), occasional whole-body fatigue during driving (OR=1.873), feeling tense during driving (OR=1.518), fatigue after work (OR=2.485), work-related stress (OR=1.882), and prolonged smartphone use with head-down posture (OR=1.671). Conversely, occasional exercise (OR=0.713)/frequent exercise (OR=0.569), driving intervals ≥21 min per round (OR=0.645), and perceiving the driving seat comfortable (OR=0.429) were associated with a lower risk of MSDs. Conclusion Physical exercise, smoking, years of service, daily cumulative driving time, driving intervals per round, prolonged smartphone use with head-down posture, self-reported health status, and psychological factors such as work-related stress are influencing factors for MSDs among bus drivers. Drivers should increase physical exercise and change unhealthy living habits. Employers should optimize working conditions, arrange reasonable driving schedules, and foster a positive work environment to reduce MSDs prevalence.

Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease. Anti-fibrosis treatment is a significant therapy for heart disease, but there is still no thorough understanding of fibrotic mechanisms. This study was carried out to ascertain the functions of cytokine receptor-like factor 1 (CRLF1) in cardiac fibrosis and clarify its regulatory mechanisms. We found that CRLF1 was expressed predominantly in cardiac fibroblasts. Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction, but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-‍β1 (TGF‍-‍β1). Gain- and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts (NMCFs) with or without TGF-‍β1 stimulation. CRLF1 overexpression increased cell viability, collagen production, cell proliferation capacity, and myofibroblast transformation of NMCFs with or without TGF‍-‍β1 stimulation, while silencing of CRLF1 had the opposite effects. An inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and different inhibitors of TGF-‍β1 signaling cascades, comprising mothers against decapentaplegic homolog (SMAD)‍-dependent and SMAD-independent pathways, were applied to investigate the mechanisms involved. CRLF1 exerted its functions by activating the ERK1/2 signaling pathway. Furthermore, the SMAD-dependent pathway, not the SMAD-independent pathway, was responsible for CRLF1 up-regulation in NMCFs treated with TGF-‍β1. In summary, activation of the TGF-‍β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression. CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway. CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.
Animals ; Humans ; Mice ; Disease Models, Animal ; Fibroblasts/metabolism* ; Fibrosis ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase 3/metabolism* ; Myocardial Infarction/metabolism* ; Receptors, Cytokine/metabolism* ; Signal Transduction ; Transforming Growth Factor beta1/pharmacology*

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Abstract Comprehensive sexuality education is an important part of quality education, primary and secondary schools are the most suitable places for sex education. This paper sorts out the current status of sexuality education for primary and secondary school students in developed countries after presenting the overall significance of school based sexuality education, and further points out the problems and urgency of sexuality education for primary and secondary school students in China. It also put forward the way to new directions for advocacy, including the comphrehensive sexuality education curriculum system, training of sexuality education teachers, the positive and active role of families, as well as social and community support for sexuality education in schools.

OBJECTIVE: To explore the genetic and clinical characteristics of near-tetraploidy/tetraploidy karyotype (NT/T) in patients with myelodysplastic syndrome (MDS). METHODS: Cytogenetic findings of 1576 inpatients with primary MDS were retrospective analyzed, among which 9 were diagnosed with NT/T. Clinical data including gender, age, morphology, genetic feature and prognosis were analyzed. RESULTS: The prevalence of MDS patients with NT/T (NT/T-MDS) among all cases was 0.57%. Karyotyping analysis suggested that eight MDS patients had sole NT/T, while the remainder one had a complex karyotype. In addition to the typical morphology of MDS, NT/T-MDS had unique morphology including huge blast, double-nuclear cell and irregular nuclear membrane. One NT/T-MDS patient gave up therapy, and the remaining eight underwent the first course of treatment, albeit with poor prognosis. Only one patient had complete remission, one had partial remission, three had no remission; and three had converted to acute myeloid leukemia. CONCLUSION NT/T-MDS is rare and has unique morphology. Generally, NT/T-MDS patients have poor prognosis. However, NT/T cannot be simply classified as high-risk group, but with consideration whether they have affected particular chromosomal structures as well as other clinical data.
Humans ; Karyotype ; Leukemia, Myeloid, Acute/complications* ; Myelodysplastic Syndromes/pathology* ; Prognosis ; Retrospective Studies ; Tetraploidy

Fluid shear stress (FSS) caused by interstitial fluid flow within trabecular bone cavities under mechanical loading is the key factor of stimulating biological response of bone cells. Therefore, to investigate the FSS distribution within cancellous bone is important for understanding the transduction process of mechanical forces within alveolar bone and the regulatory mechanism at cell level during tooth development and orthodontics. In the present study, the orthodontic tooth movement experiment on rats was first performed. Finite element model of tooth-periodontal ligament-alveolar bone based on micro computed tomography (micro-CT) images was established and the strain field in alveolar bone was analyzed. An ideal model was constructed mimicking the porous structure of actual rat alveolar bone. Fluid flow in bone was predicted by using fluid-solid coupling numerical simulation. Dynamic occlusal loading with orthodontic tension loading or compression loading was applied on the ideal model. The results showed that FSS on the surface of the trabeculae along occlusal direction was higher than that along perpendicular to occlusal direction, and orthodontic force has little effect on FSS within alveolar bone. This study suggests that the orientation of occlusal loading can be changed clinically by adjusting the shape of occlusal surface, then FSS with different level could be produced on trabecular surface, which further activates the biological response of bone cells and finally regulates the remodeling of alveolar bone.

Objective To study fluid flow within alveolar bone under orthodontic and occlusal loading, so as to provide references for understanding the regulatory mechanism of bone remodeling during orthodontics. Methods An animal model for orthodontic tooth movement on rats was first constructed. The finite element model of tooth-periodontal ligament-alveolar bone was established based on micro-CT images and the strain field in alveolar bone under orthodontic or constant occlusal loading was analyzed. Then finite element model of alveolar bone was constructed from the bone near the cervical margin or apical root of mesial root. The fluid flow in this model under orthodontic and cyclic occlusal loading was further predicted by using fluid-solid coupling numerical simulation. Results The fluid velocity within alveolar bone cavity mainly distributed at 0-10 μm/s, and the fluid shear stress (FSS) was mainly distributed at 0-10 Pa. FSS on the surface of alveolar bone near the apical root was higher than that close to the cervical margin. Conclusions FSS at different levels could be produced at different location within alveolar bone cavity under orthodontic and cyclic occlusal loading, which might further activate biological response of bone cells on the surface of trabeculae and finally regulate the remodeling of alveolar bone and orthodontic movement of tooth. The results provide theoretical guidance for the clinical treatment of orthodontics.

Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-γ, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.
Animals ; Carcinoma, Non-Small-Cell Lung ; immunology ; therapy ; Cell Line, Tumor ; ErbB Receptors ; immunology ; metabolism ; Female ; Humans ; Immunotherapy, Adoptive ; methods ; Lung Neoplasms ; immunology ; therapy ; Mice ; Mice, Inbred NOD ; Receptors, Chimeric Antigen ; immunology ; T-Lymphocytes ; immunology ; Xenograft Model Antitumor Assays

Objective Benzothiazole derivative BD960 has immunosuppressive activity after cell -based assays for high-throughput screening.The paper aimed to investigate the involved mechanism of BD960 on T cell proliferation. Methods Human peripheral blood T-lymphocytes were isolated and purified by the immunomagnetic microbeads.Then the T cells were activated by anti-CD3/anti-CD28 mAbs or alloantigen.The effect of BD960 on activa-ted T cell proliferation, the cytotoxic effect BD960 on resting T cells and the expression of activated T cells marker CD25 were measured by flow cytometer.Cytokine levels, including IL-2, IL-4, IL-6, IL-10, IL-17A and IFN-γ, were determined by ELISA. Results BD960 significantly inhibited the proliferation of T cells stimulated by anti-CD3/anti-CD28 mAb or alloantigen in a dose-dependent manner.The IC50 value is (2.3 ±0.3)μmol/L or (2.5 ±0.3)μmol/L, respectively.Moreover, BD960 had no obvious cytotoxic effects on rest-ing T cells and peripheral blood mononuclear cells, even at a high concentration ( up to 100μmol/L) .The ratio of CD25 expression on T cell was 69.7%after stimulated by Anti-CD3/CD28 mAbs with 72 h, the concentration (0.625、2.5、10)μmol/L of BD960 also had no potent effects on the ratio, but 0.1μmol/L FK506 could inhibit CD25 expression as low as 9.4%.The G0/G1 phase of activated T cells was 58.5%after stimulated by BD960 with 96 h.BD960 could induce cell cycle arrest at the G0/G1 phase in activated T cells with the increase of concentration and RAPA in the concentration of 0.1 μmol/L was 91.5%.In addition, BD960 (0.625、2.5、10)μmol/L could inhibit the secretion of IFN-γ, IL-6 and IL-17 in activated T cells with the increase of concentration, without any effects on the secretion of IL-2, IL-4 and IL-10. Conclusion BD960 not only exerts the inhibition on the late stage of T cell activation of cell proliferation but also inhibits the secretion of inflammatory cytokines, such as IL-6, IL-17 and IFN-γ, while the mechanism of BD960 on T cell proliferation was not the same as FK506.As a result, BD960 has the potential to be the lead compound to develop a new immunosuppressant.

Objective To investigate the incidence and influencing factors of aldosterone escape in patients with non-diabetic nephropathy by RASI-therapy. Methods A total of 104 patients with non-diabetic nephropathy were treated with ARB or combination therapy of ACEI and ARB in a mean follow-up period of 12 months. Aldosterone escape was determined according to the change of plasma aldosterone concentration before and after treatment during 6-month and 12-month ACEI/ARB treatment, while the influencing factors of aldosterone escape in patients with non-diabetic nephropathy was also analyzed after therapy with RASI . Results In 12 months, the incidence of aldosterone escape was significantly higher than that in 6 months (26.92% vs. 14.42%, P = 0.007). After 12-month treatment, the difference was statistically significant in incidence of aldosterone escape among different stages of CKD (P = 0.027). Compared with 6-month incidence of aldosterone escape in the losartan group, 12-month incidence increased evidently (P = 0.020). The Ald level was positively correlated with urinary protein excretion and the Scr level (r = 0.431, P = 0.003 and r = 0.336, P = 0.009, respectively), and negetively correlated with levels of the eGFR (r = -0.275, P = 0.006). Univariate Logistic regression demonstrated that risk factors of aldosterone escape included pre-treatment values of the urinary protein excretion (OR = 3.671, P = 0.028) and the eGFR (OR = 0.972, P = 0.019). Multivariate Logistic model revealed pre-treatment values of the eGFR was positively associated with aldosterone escape (OR = 0.970, P = 0.012). Conclusion The incidence of the aldosterone escape increases along with the time of treatment. Renal function has correlated with aldosterone escape and pre-treatment value of the eGFR is an independent risk factor of aldosterone escape.