The αPD-L1 antibody-based immune checkpoint blockade therapy is still limited by the poor clinical response rate as it is mainly utilized to block surface PD-L1 on tumor cells while ignoring abundant PD-L1 exosomes secreted in the environment, causing tumor immune evasion. Here, we proposed an exosome biogenesis inhibition strategy to suppress tumor exosomes secretion from the source, reducing the inhibitory effect on T cells and enhancing chemo-immunotherapy efficacy. We developed sulfafurazole homodimers (SAS) with disulfide linkages, effectively releasing the drug in response to glutathione (GSH) and inhibiting 4T1 tumor-derived exosomes secretion. Subsequently, gemcitabine (Gem) was encapsulated to induce immunogenic cell death (ICD). Consequently, Gem@SAS inhibited the secretion of tumor exosomes by more than 70%, increased proliferation and granzyme B secretion ability of T cells by more than 2 times, and showed superior efficacy in breast cancer treatment as well as lung metastasis of breast cancer.

Mesenchymal stem cells (MSCs) have been widely used in the treatment of various autoimmune and inflammation-related diseases due to their potent immunomodulatory properties. Several studies have demonstrated that MSC-mediated immunomodulation is complex and bidirectional, with the in vivo microenvironment influencing the direction of this modulation. Indoleamine-2,3-dioxygenase (IDO), an immunosuppressive factor, has been identified as a key "switch" in the immunomodulatory role of MSCs. In this review, we explore how IDO functions as a critical regulator of MSC immunoregulatory plasticity. We delve into the mechanisms by which changes in IDO expression affect the function of various immune cells, summarize relevant research and clinical advances regarding the role of IDO expression in MSC-based therapies for various diseases, and discuss potential therapeutic strategies that target IDO to enhance the stability of MSC therapeutic effects. This provides a theoretical foundation for optimizing MSCs as safer and more effective clinical therapeutic agents.

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Objective To observe the clinical efficacy of Tongyuan acupuncture in the treatment of acute gouty arthritis.Methods A total of 126 cases of patients with definitive diagnosis of acute gouty arthritis admitted to the wards and outpatient clinics of Guangzhou Nansha District Hospital of Traditional Chinese Medicine from November 2023 to June 2024 were selected as the study subjects.The patients were randomly divided into observation group and control group according to the random number table method,with 63 cases in each group.The control group was given health training and conventional treatment,while the observation group was given Tongyuan acupuncture on the basis of treatment in the control group.Patients in both groups were treated for 14 consecutive days.After two weeks of treatment,the clinical efficacy of the two groups was evaluated.The changes in the clinical symptom scores,the Visual Analogue Scale(VAS)scores of pain,the levels of musculoskeletal ultrasonography(synovial proliferation,blood flow signals,and joint fluid)before and after the treatment were observed in patients of both groups.The changes of blood uric acid(UA),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),tumor necrosis factor α(TNF-α),and interleukin 1(IL-1)before and after treatment were compared between the two groups.Results(1)The total effective rate was 95.24%(60/63)in the observation group and 84.13%(53/63)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(2)After treatment,the clinical symptom scores and VAS scores of the patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(3)After treatment,the serum UA,ESR,and CRP levels of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(4)After treatment,the TNF-α and IL-1 levels of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(5)After treatment,the musculoskeletal ultrasound indicators of the two groups of patients were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).Conclusion Tongyuan acupuncture in the treatment of acute gouty arthritis can significantly improve the clinical symptoms of patients,reduce the level of patients'blood UA and inflammatory factor.

Humans ; Amyloidosis ; Amyloid ; Cardiomyopathies

Objective To investigate the effect of multi-sided foramen ultrafine drainage tube with metal support on the formation of thoracic residual cavity after uniportal video-assisted thoracoscopic (VATS) upper lobectomy. Methods The clinical data of the patients who underwent uniportal VATS upper lobectomy for lung cancer in the Department of Thoracic Surgery of the First Hospital of Lanzhou University from January 2021 to April 2022 were retrospectively analyzed. According to the type of ultrafine drainage tube used in the surgery, the patients were divided into a test group (using metal-supported multi-sided foramen ultrafine drainage tube) and a control group (using ordinary 12F ultrafine drainage tube). The incidence of postoperative thoracic residual cavity and operation-related data were compared between the two groups. Results A total of 200 patients were enrolled, including 126 males and 74 females, with a mean age of 57.52 years. There were 90 patients in the test group, and 110 patients in the control group. The incidence of postoperative thoracic residual cavity in the test group was lower than that in the control group (P=0.045). The differences in the postoperative bedtime, postoperative visual analogue scale, postoperative analgesic pump using time, postoperative hospitalization time, times of postoperative thoracentration and drainage, postoperative drainage time and hospitalization cost between the two groups were statistically significant (P<0.05). The incidences of postoperative lung infection, pleural effusion and atelectasis complications were lower in the test group than those in the control group (P<0.05). The differences in the preoperative anesthesia time, operation time, intraoperative bleeding and postoperative lung leakage were not statistically significant (P>0.05). Conclusion The use of multi-sided foramen ultrafine drainage tube with metal support can reduce the incidence of thoracic residual cavity after uniportal VATS upper lobectomy, and can reduce pain and economical burdens and the incidence of operation-related complications, accelerating the recovery of patients after surgery. The application of multi-sided foramen ultrafine drainage tube with metal support in uniportal VATS upper lobectomy can be widely used in the clinic.

Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and is an important cause for cancer death. Although the application of immunotherapy in recent years has greatly improved the prognosis of NSCLC, there are still huge challenges in the treatment of NSCLC. The immune microenvironment plays an important role in the process of NSCLC development, infiltration and metastasis, and they can interact and influence each other, forming a vicious circle. Notably, single-cell RNA sequencing enables high-resolution analysis of individual cells and is of great value in revealing cell types, cell evolution trajectories, molecular mechanisms of cell differentiation, and intercellular regulation within the immune microenvironment. Single-cell RNA sequencing is expected to uncover more promising immunotherapies. This article reviews the important researches and latest achievements of single-cell RNA sequencing in the immune microenvironment of NSCLC, and aims to explore the significance of applying single-cell RNA sequencing to analyze the immune microenvironment of NSCLC.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Background::The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.Methods::This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.Results::The optimal cut-off values of L3-SMI were 39.50 cm 2/m 2 for male patients and 33.06 cm 2/m 2 for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis ( Wald = 6.347, P = 0.012). Conclusions::This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.

Background There are a variety of microorganisms in ambient air, and susceptible people can be infected once contact with pathogenic microorganisms in the environment. In order to avoid the spread of pathogenic bacteria, disinfection is the simplest and most effective way of killing pathogenic bacteria in the environment to block the contact between pathogenic bacteria and humans. Sodium hypochlorite (NaClO) is the most widely used disinfectant, but its safety in ambient air disinfection is not clear yet. Objective To establish a model of bronchial epithelial cell (BEAS-2B) injury induced by NaClO, and to explore the mechanism of the toxic effect of NaClO disinfectants on BEAS-2B. Methods Cells were treated with concentration gradients of 0, 25, 50,100, 200, and 400 μmol·L⁻¹ of the diluted NaClO (100 mmol·L⁻¹) standard solution, respectively, and cell activity was measured by cell counting kit-8 (CCK-8) assay after 15 and 30 min. Cells treated with 0, 25, and 50 μmol·L⁻¹ NaClO were selected to observe the cell morphology under an inverted microscope, apoptosis was determined by flow cytometry Annexin V FITC / PI double staining to determine the final experimental concentration. The morphology of organelles such as mitochondria was observed under a transmission electron microscope. Mitochondrial membrane potential of the cells was detected by JC-1 staining. Intracellular Ca²⁺ concentration was measured with a Fluo-4 AM fluorescent probe. Total cellular reactive oxygen species (ROS) was detected with a 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe, cell mitochondrial ROS with a dihydroethidium (DHE) fluorescent probe, and lipid peroxidation intermediate malondialdehyde (MDA) with a commercial kit. Results Compared with 0 μmol·L⁻¹, NaClO treatment group, cell morphology did not change a lot after 25 μmol·L⁻¹ NaClO treatment for 30 min, and the cells began to wrinkle and become round after 30 min treatment with 50 μmol·L⁻¹ NaClO, showing about 70% of normal cell viability (P<0.01). So 30 min 50 μmol·L⁻¹ NaClO treatment was selected for the subsequent experiment. The experimental results found that compared with the 0 μmol·L⁻¹ NaClO treatment group, the number of apoptotic cells increased (P<0.05), the mitochondrial membrane potential decreased (P<0.01), the intracellular Ca²⁺ concentration increased (P<0.05), the cellular ROS level increased (P<0.05), the mitochondrial ROS level increased (P<0.01), and the MDA content increased (P<0.01) in the NaClO treatment group.. Conclusion The study has successfully established a model of BEAS-2B injury induced by NaClO, and found that NaClO can lead to cell damage by inducing apoptosis and oxidative stress in BEAS-2B cells. According to the results, there are two possible reasons. First, NaClO solves in water to form hypochlorous acid (HClO) which is oxidative and increases the intracellular ROS level after entering cells, leading to cellular oxidative stress. Second, HClO enters cells to directly attack the mitochondrial membrane, resulting in the imbalance of potential inside and outside the mitochondrial membrane, and apoptosis caused by Ca²⁺ efflux.