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 analyze the association between healthy lifestyle and mortality among Henan Province 35-74 years old individuals.Methods:Data from the programme of screening and intervention subjects with high-risk cardiovascular disease 99 133 adults were analyzed in a provincial cohort study of 16 counties. Four healthy lifestyle behaviors were assessed based on a questionnaire survey. Information on mortality endpoints was retrieved from the national death surveillance system. Cox proportional hazards regression models were used to estimate the associations between healthy lifestyles, mortality risk and population attributable fraction (PAF).Results:Out of the adult participants in Henan, 50.6% adhered to a healthy lifestyle, and only 0.1% adhered to 4 healthy lifestyle behaviours. During a mean of 4.5 years, 2 685 all-cause death and 1 283 cardiovascular deaths were documented. The decreased risk of mortality among individuals with non-smoking, moderate drinking, adequate exercise and healthy diet were 0.85 (95% CI: 0.77-0.94), 0.75 (95% CI: 0.63-0.89), 0.73 (95% CI: 0.67-0.79) and 0.86 (95% CI: 0.77-0.96), while the adjusted PAF for all-cause deaths were 5.2% (95% CI: 2.5%-7.9%), 24.0% (95% CI: 10.7%-36.4%), 19.4% (95% CI: 13.8%-24.8%) and 12.3% (95% CI: 3.4%-20.9%), respectively. A combined healthy lifestyle can bring more health benefits. Adherence to 4 healthy lifestyle behaviours could avoid 49.1% of all-cause death. Conclusion:Adherence to a healthy lifestyle can reduce the risk of death, and participants with a healthy lifestyle had a lower mortality risk.

Humans ; Amyloidosis ; Amyloid ; Cardiomyopathies

Objective To investigate the effect of laser engraving personalized nasal patch applied to patients with nasal catheter indentation.Methods A total of 124 patients who underwent esophageal cancer surgery in the First Hospital of Lanzhou University from February 2022 to February 2023 and required indwelling nasal catheter were selected as study objects,and were divided into experimental group and control group according to random number table method,with 62 cases in each group.The control group used conventionally cut nasal patches to fix the nasal catheters,and the experimental group used laser engraved personalized nasal patches.Catheter displacement or slippage under the fixation device,nasal patch rolled edges and number of replacement,nasal medical device-related pressure injury,medical adhesive-related skin lesions and patients'comfort were observed in two groups.Results The rate of catheter displacement,number of rolled edges of nasal patches and numbers of replacement in experimental group were significantly lower than those in control group(P<0.05).The incidence of nasal mucosal indentation,nasal pain,nasal pressure injury and medical adhesive related skin lesions in experimental group were significantly lower than those in control group(P<0.05).The comfort of patients at the physiological level of experimental group was significantly better than that of control group(P<0.05).Conclusion Laser engraved personalized nasal patches can reduce the frequency of clinical nasal catheter displacement,nasal patch rolled edges and number of replacement,reduce the occurrence of nasal medical device related pressure injuries and medical adhesive-related skin lesions,and increase patients'comfort.

Objective To investigate the clinical effect of metal supported multi-sided versus ordinary ultra-fine drainage tube in the uniportal video-assisted thoracic surgery (VATS) lower pulmonary lobectomy. Methods From January 2021 to June 2022, the clinical data of patients who underwent uniportal VATS lower lobectomy in our hospital were retrospectively analyzed. According to the different types of ultra-fine drainage tubes used in the surgery, the patients were divided into an experimental group (using multi-sided hole 10F ultra-fine drainage tubes with metal support) and a control group (using ordinary 12F ultra-fine drainage tubes). The clinical data of the two groups were compared. Results A total of 190 patients were enrolled, including 108 males and 82 females. There were 90 patients in the experimental group aged 56.60±10.14 years; and 100 patients in the control group aged 57.07±11.04 years. The incidences of postoperative lung infection and pleural effusion in the experimental group were lower than those in the control group, with statistically significant differences (P<0.05). The postoperative visual analogue scale score, the need to adjust the chest drainage tube after the surgery, the need for chest puncture after the surgery, the time of postoperative chest tube removal, and the hospitalization cost were statistically different (P<0.05). There was no statistical difference in the length of postoperative hospital stay or the incidences of postoperative lung leakage, arrhythmia, and atelectasis complications (P>0.05). Conclusion Compared with the ordinary ultra-fine drainage tubes, multi-sided hole ultra-fine drainage tubes with metal support can reduce the incidences of lung infection and pleural effusion complications after the uniportal VATS lower lobectomy, reduce the pain and economic burden, which can be applied in the uniportal VATS lower lobectomy.

Objective To analyze the long-term outcome of modified Morrow surgery (interventricular septal cardiomyectomy) in the treatment of hypertrophic obstructive cardiomyopathy (HOCM) in children. Methods The clinical data of the children with HOCM (aged≤14 years) who underwent modified Morrow surgery from January 2010 to August 2022 in Guangdong Provincial People's Hospital were retrospectively analyzed, including changes in hospitalization status, perioperative period, and long-term 15-lead electrocardiogram and echocardiography. Results A total of 29 patients were collected, including 22 males and 7 females, aged 10.00 (5.00, 12.00) years. Five (17.9%) patients had New York Heart Association (NYHA) heart function grade Ⅲ or Ⅳ. Ventricular septal cardiomyectomy was performed in all patients. All 29 patients survived and their cardiac function recovered after operation. Before discharge, right bundle branch block was observed in 2 patients and left bundle branch block in 6 patients. After surgery, in the left ventricular septal cardiomyectomy, the left atrial diameter decreased (P＜0.001), left ventricular end-systolic diameter increased (P=0.009), the peak pressure gradient of left ventricular outflow tract decreased (P＜0.001), and the thickness of ventricular septum decreased (P＜0.001). The systolic anterior motion of mitral valve disappeared and mitral regurgitent jet area decreased (P＜0.001). The flow velocity and peak pressure gradient of right ventricular outflow tract also decreased in the patients who underwent right ventricular septal cardiomyectomy. The average follow-up of the patients was 69.03±10.60 months. All the patients survived with their NYHA cardiac function grading Ⅰ or Ⅱ. No new-onset arrythmia event was found. Echocardiography indicated that the peak pressure gradient of the left ventricular outflow tract remained low (P<0.001). Moderate mitral regurgitation occurred in 2 patients, and left ventricular outflow tract obstruction with moderate mitral regurgitation occurred in 1 patient after simple right ventricular septal cardiomyectomy. Conclusion Right ventricular or biventricular obstruction is frequent in the children with HOCM and they usually have more symptoms before surgery. Modified Morrow surgery can effectively relieve outflow tract obstruction and improve their cardiac function. The long-term outcome is satisfactory. However, the posterior wall of the left ventricle remains hypertrophic. Also, there is an increased risk of a conduction block.

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.

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.