Cardiovascular disease represent a significant global health threat,featured with continuously increased morbidity and mortality rates worldwide in recent years.Consequently,there is an urgent need for the development of safe and effective novel approaches for the prevention and treatment of cardiovascular disease.The advancements in nanotechnology within the medical field,including drug delivery and molecular imaging,have opened innovative avenues for the diagnosis and treatment of diseases.Due to their unique physicochemical and biological properties,metal-based nanoparticles have demonstrated remarkable potential and broad prospects in the diagnosis and treatment of cardiovascular disease.This review summarizes the latest research developments in the application of metal-based nanoparticles in cardiovascular disease and discusses the challenges associated with their clinical application,and presents new insights for the individualized and precise diagnosis and treatment of cardiovascular disease.

Objective:To investigate the application effect of quadratus lumborum block (QLB) combined with less opioid anesthesia analgesia in laparoscopic total hysterectomy (LTH) in elderly patients with uterine prolapse.Methods:A total of 86 elderly patients with uterine prolapse who received LTH in the Langfang People’s Hospital from Jan. 2021 to Oct. 2023 were prospectively selected and divided into group A ( n=42) and group B ( n=44) according to the random number table method. Group A received transversus abdominis block (TAPB) + general anesthesia, and group B received QLB combined with less opioid anesthesia + general anesthesia. The pain duration at different time points after operation [Numeric Rating Scale (NRS) method to evaluate resting incision and visceral pain] was compared between the two groups. The dosage of opioids and the additional analgesia rate were compared between the two groups. The sleep quality of the two groups before and 72 hours after operation was compared, and the adverse reactions of anesthesia were counted. Results:Compared with 6 h after operation, NRS scores of resting incision pain and visceral pain in the two groups decreased gradually at 12, 24 and 48 h after operation, and it was lower in group B than in group A. There were statistically significant differences between groups ( P<0.05) . Dosage of sufentanil and remifentanil in group B was lower than that in group A, and the postoperative additional analgesia rate in group B (9.09%) was lower than that in group A (28.57%) ( P<0.05) . 72 hours after surgery, the sleep efficiency and total sleep time of patients in both groups were lower than those before surgery, and they were higher in group B than in group A; The awakening time and number of awakenings in both groups were higher than those before surgery, while they were lower in group B than in group A ( P<0.05) . The total incidence of adverse reactions in group B was 4.76% (2/44) , lower than 23.81% (10/42) of group A ( P<0.05) . Conclusion:QLB combined with less opioid anesthesia analgesia can effectively reduce the degree of incision and visceral pain after LTH in elderly patients with uterine prolapse, reduce the amount of opioids used during operation and the rate of additional analgesia, and reduce the incidence of adverse reactions of anesthesia.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Background Air pollution remains a critical public health issue, with persistent exposure to air pollutants continuing to pose significant health risks. Currently, research investigating the association between air pollution and myocardial infarction mortality in Shenzhen remains inadequate. Objective To quantitatively assess the association between air pollutants and myocardial infarction mortality in residents. Methods Based on the mortality surveillance system of Shenzhen Center for Disease Control and Prevention, we conducted a time-stratified case-crossover study of 10089 permanent residents who died from myocardial infarction in Shenzhen between 2013 and 2022. Using residential address information, we obtained individual-level exposure data for air pollutants from the China High Air Pollutants dataset and meteorological factors from the China Meteorological Administration Land Data Assimilation System. A time-stratified case-crossover study design was employed to construct a conditional logistic regression model to assess the association between short-term exposure to air pollutants and myocardial infarction mortality. The exposure-response relationship was visualized, and a comprehensive health risk assessment was performed. Results This study included a total of 10 089 cases of myocardial infarction deaths in Shenzhen. The median [interquartile range (IQR)] concentrations of fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and ozone (O₃) in Shenzhen from 2013 to 2022 were 24.59 (20.19) μg·m⁻³, 42.85 (28.42) μg·m⁻³, 8.53 (3.39) μg·m⁻³, 29.47 (13.56) μg·m⁻³, 0.77 (0.27) mg·m⁻³, and 86.53 (51.39) μg·m⁻³, respectively. The moving average concentrations of PM_2.5 and PM₁₀ over the current day and the previous 2 days (lag02) showed the highest risk of myocardial infarction mortality, with an odds ratio (OR) and 95% confidence interval (95%CI) of 1.004 (1.001, 1.007) and 1.004 (1.002, 1.006), respectively. At lag05, SO₂ demonstrated the strongest association with the risk of myocardial infarction mortality, with an OR (95%CI) of 1.042 (1.019, 1.065). The exposure-response relationships of PM_2.5, PM₁₀, and SO₂ with myocardial infarction mortality were approximately linear, whereas NO₂ exhibited a nonlinear relationship. At lag05, the highest risk of myocardial infarction mortality associated with NO₂ exposure was observed when the NO₂ concentration was ≤21.92 μg·m⁻³, with an OR (95% CI) of 1.024 (1.003, 1.046). The health risk assessment indicated that, using the WHO Air Quality Guidelines as the reference, the local PM_2.5 and NO₂ exposure led to an excess mortality of 398 and 298 cases, respectively. The sensitivity analysis revealed that after adjusting for O₃ and restricting the study period to 2013—2019, the effect estimates for PM_2.5, PM₁₀, NO₂, and SO₂ on myocardial infarction mortality slightly increased. Conclusion Short-term exposure to air pollutants, including PM_2.5, PM₁₀, NO₂, and SO₂, could increase the risk of myocardial infarction mortality. This study provides important scientific evidence for environmental health risk assessment and environmental management in Shenzhen.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Objective The aim of this study was to clarify the role and mechanism of Pseudomonas aeruginosa vaccine subunit OprI in the fusion protein vaccine rePO(PcrV-OprI).Methods The in vitro stability of rePO,PcrV and OprI at 4 ℃,25 ℃,and 37 ℃ was examined.After immunizing mice with rePO,OprI and PcrV,respectively,the specific antibody potency in serum and the proportion of cells secreting IFN-γ and IL-4 in the spleen were examined;Additionally,detection of the levels of protein uptake by DC2.4 cells in vitro using laser confocal microscopy and flow cytometry,and their ability to promote the maturation of mouse bone marrow-derived dendritic cells(BMDC).Results The heat stability of fusion protein rePO was significantly better than that of PcrV.The induced anti-PcrV IgG and anti-OprI IgG potency of rePO was significantly higher than that of monomeric PcrV and OprI.Additionally,the number of cells secreting IFN-γ and IL-4 induced by immunization with rePO was significantly higher than that of PcrV and OprI.The uptake rate of fusion protein rePO by DC2.4 cells was significantly higher than that of PcrV and OprI.Furthermore,rePO promoted the maturation of mouse BMDC more effectively than PcrV and OprI.Conclusion OprI in the fusion protein rePO can significantly improve its thermal stability and immunogenicity,which lays the foundation for the successful development of Pseudomonas aeruginosa vaccine.

Objectives:This study aimed to observe the disintegration of clopidogrel and ticagrelor in vitro solution with different pH levels and in human digestive tract.Methods:(1)In vitro study:0.9% normal saline was mixed with hydrochloric acid and sodium bicarbonate respectively to mimic fasting gastric fluid,postprandial gastric fluid,gastric fluid after taking acid-inhibiting agent,acid-free gastric fluid and small intestine fluid.The disintegration of clopidogrel and ticagrelor in different pH solutions was observed.(2)In vivo study:12 patients who were admitted to the Department of Geriatric,Peking University First Hospital from 2022.11 to 2023.6 were included and underwent magnetic controlled capsule endoscopy.We observed the disintegration of clopidogrel(n=6)and ticagrelor(n=6)in the digestive tract.Results:(1)In vitro study:clopidogrel began to disintegrate earlier than ticagrelor([21.67±7.53]s vs.[40.00±6.33]s,P=0.001),but clopidogrel disintegrated more slowly than ticagrelor([23.00±9.38]min vs.[8.33±1.97]min,P=0.011).Clopidogrel disintegrated faster in alkaline solution than in acidic and neutral solution([11.50±4.95]min vs.[28.75±2.50]min,P=0.004),and the disintegration rate of ticagrelor in alkaline solutions is comparable to that in acidic and neutral solutions([7.00±1.41]min vs.[9.00±2.00]min,P=0.285).(2)In vivo study:In the study population,the morphology of clopidogrel and ticagrelor began to change after passing through the esophagus,of which 3 cases(clopidogrel 1 case,ticagrelor 2 cases)were in powder state when passing through the cardia,and the remaining 9 cases were basically intact when entering the stomach and completely disintegrated in the stomach.The complete disintegration time of Clopidogrel varied significantly among individuals,ranging from 8 to 33 min,with an average of(18.80±10.38)min,while the complete disintegration time of ticagrelor ranged from 3 to 6 min,with an average of(4.25±1.26)min.Clopidogrel disintegrated slower than ticagrelor(P=0.034).Conclusions:In vitro study,clopidogrel disintegrated more slowly than ticagrelor in solutions at different pH levels.Compared with clopidogrel,the disintegration rate of ticagrelor was less affected by pH.After oral administration of clopidogrel and ticagrelor,clopidogrel disintegrated more slowly than ticagrelor.The difference of complete disintegration time between individuals of ticagrelor was smaller and the disintegration rate was faster.

Objective:To investigate the application effect of quadratus lumborum block (QLB) combined with less opioid anesthesia analgesia in laparoscopic total hysterectomy (LTH) in elderly patients with uterine prolapse.Methods:A total of 86 elderly patients with uterine prolapse who received LTH in the Langfang People’s Hospital from Jan. 2021 to Oct. 2023 were prospectively selected and divided into group A ( n=42) and group B ( n=44) according to the random number table method. Group A received transversus abdominis block (TAPB) + general anesthesia, and group B received QLB combined with less opioid anesthesia + general anesthesia. The pain duration at different time points after operation [Numeric Rating Scale (NRS) method to evaluate resting incision and visceral pain] was compared between the two groups. The dosage of opioids and the additional analgesia rate were compared between the two groups. The sleep quality of the two groups before and 72 hours after operation was compared, and the adverse reactions of anesthesia were counted. Results:Compared with 6 h after operation, NRS scores of resting incision pain and visceral pain in the two groups decreased gradually at 12, 24 and 48 h after operation, and it was lower in group B than in group A. There were statistically significant differences between groups ( P<0.05) . Dosage of sufentanil and remifentanil in group B was lower than that in group A, and the postoperative additional analgesia rate in group B (9.09%) was lower than that in group A (28.57%) ( P<0.05) . 72 hours after surgery, the sleep efficiency and total sleep time of patients in both groups were lower than those before surgery, and they were higher in group B than in group A; The awakening time and number of awakenings in both groups were higher than those before surgery, while they were lower in group B than in group A ( P<0.05) . The total incidence of adverse reactions in group B was 4.76% (2/44) , lower than 23.81% (10/42) of group A ( P<0.05) . Conclusion:QLB combined with less opioid anesthesia analgesia can effectively reduce the degree of incision and visceral pain after LTH in elderly patients with uterine prolapse, reduce the amount of opioids used during operation and the rate of additional analgesia, and reduce the incidence of adverse reactions of anesthesia.

Objective:Surgical site infection (SSI) is a common health care-related infection after gastrointestinal surgery. Once SSI occurs after surgery, it can significantly prolong the postoperative hospital stay, increase the cost burden of patients and society, and even endanger the life safety of patients. The purpose of this study was to investigate the clinical phenotypes of gastrointestinal surgery, identify the clinical characteristics of SSI, and provide reference for the prevention of SSI after gastrointestinal surgery.Methods:This is a multicenter prospective cohort study that collected clinical data from all adult patients undergoing gastrointestinal surgery from March 2021 to February 2022 at 42 hospitals in China, including baseline and perioperative characteristics. Based on the variables associated with SSI, latent class analysis (LCA) was used to explore the population characteristics of SSI.Results:In total, 16 087 patients were included in the study, of whom 345 (2.1%) developed SSI. LCA analysis revealed that patients undergoing gastrointestinal surgery were classified into four clinical phenotypes, including α (3851), β (1538), γ (6387), and δ (4311). Type α had minimal abnormality on related system functions (ASA score > 2: 4.5% [173/3851]), and mainly underwent appendix surgery (98.9% [3808/3851]). The postoperative SSI incidence of type α was 0.4% (16/3,851), which belonged to the group of SSI low risk. The abnormality of system functions of type β (ASA score > 2: 17.4% [268/1538]) was worse than that of type α. Type β mainly underwent stomach surgery (72.4% [1113/1538]), and its incidence of postoperative SSI was 1.2% (18/1538), belonging to the group of SSI medium risk. The ASA score of type γ (ASA score > 2: 18.0% [1148/6387]) was comparable to that of type β. Type γ mainly received colorectal surgery (colon surgery: 40.1% [2562/6387]; rectal surgery: 33.6%[2143/6387]), and its incidence of postoperative SSI was 1.7% (106/6387), belonging to the group of SSI medium risk. Type δ (ASA score > 2: 23.5%[1015/4311]) was the most serious type with the highest proportion of open surgery. Type δ mainly underwent small intestine (54.0%[2327/4311]) and stomach surgery (32.3% [1392/4311]) and had the highest incidence of SSI (4.8% [205/4311]) and the highest mortality rate (0.6% [24/4311]), belonging to the group of SSI high risk. Compared with type α and β, the median length of hospital stay (α, β, γ, and δ: 5.0 days, 9.6 days, 13.0 days, and 16.0 days, P<0.001) and postoperative hospital stay (α, β, γ, and δ: 4.0days, 6.0days, 8.3 days, and 10.0 days, P<0.001) of type γ and δ were significantly increased, and the median medical costs (α, β, γ, and δ: 14 178.7 yuan, 39 514.2 yuan, 62 893.0 yuan and 57 266.6 yuan, P<0.001) were also significantly increased. Conclusion:LCA analysis elucidated four clinical phenotypes of patients undergoing gastrointestinal surgery. Type α had a low risk of SSI. Type β and γ had a medium risk of SSI, and type δ had a high risk of SSI.

Atherosclerosis is a severe disease threatening human health,leading to tremendous consequences such as acute coronary syndrome,myocardial infarction,and stroke.The onset and progression of atherosclerosis are attributed to a chronic inflammatory process,closely associated with the biological activities of various cells.Calpain,a Ca2+-dependent cysteine protease within cells,plays a pivotal role in this context by regulating a plethora of substrates through restricted catalysis of protein hydrolysis,thereby participating in pathological and physiological processes including endothelial damage,inflammatory response,and lipid metabolism.This review summarizes the role of calpain in the development of atherosclerosis and the latest research progress in the application of calpain inhibitors for treatment of atherosclerosis,offering new insights for the clinical realization of personalized and precise treatment of atherosclerosis.