Objective To investigate the effects of exosomes (Exo) derived from high glucose-stimulated glomerular mesangial cells (GMC) on the kidneys of C57BL/6 mice and the intervention mechanism of Tongluo Yishen Formula (TLYSF). Methods The rat GMC were divided into a normal glucose group (NG, with 5.6 mmol/L glucose) and a high glucose group (HG, with 30 mmol/L glucose). After 24 hours of culture, the supernatant was collected, and exosomes were extracted using the ultracentrifugation method. The exosomes were then identified by transmission electron microscopy and Western blot analysis. Male C57BL/6 mice were divided into three groups: NO-Exo group, NG-Exo group, and HG-Exo group. These groups were respectively administered tail vein injections of PBS buffer, exosomes derived from GMC cultured in normal glucose, and exosomes derived from GMC cultured in high glucose, three times a week for a total of 8 weeks. After 8 weeks, the mice in the HG-Exo group were randomly divided into three subgroups: the HG-Exo group [gavaged with saline], the HG-Exo+TLYSF group [gavaged with TLYSF at 34.32 g/(kg.d)], and the HG-Exo + VAL group [gavaged with valsartan suspension at 10.4 mg/(kg.d)], and the intervention lasted for 4 weeks. Urinary microalbumin (mALb), urinary N-acetyl-β-D-aminoglucosidase (NAG), glycated hemoglobin (HbA1c), serum creatinine (Scr) and urea nitrogen (BUN) were detected. Transmission electron microscopy was used to observe the ultrastructure of renal tissues. TUNEL was used to detect the DNA damage of renal tissue cells. Immunofluorescence was used to detect the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and wilms tumor 1(WT-1). RT-PCR was used to detect the mRNA levels of NLRP3, cysteinyl aspartate-specific proteinase 1 (caspase-1), interleukin-1 beta (IL-1β), miR-200c-3p and miR-148a-3p. Western Blot was employed to detect the protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 and IL-1β. Results Compared with the NG-Exo group, mice in the HG-Exo group exhibited significantly increased levels of mALb, urinary NAG, Scr and BUN. Transmission electron microscopy revealed ruptured podocyte membranes and swollen mitochondria. The positive rate of cells stained by the TUNEL increased, with elevated optical density of NLRP3 and decreased optical density of WT-1. Additionally, there was a significant increase in the level of NLRP3, caspase-1, IL-1β mRNA, as well as miR-200c-3p and miR-148a-3p. The protein expression of NLRP3, ASC, caspase-1, and IL-1β also increased. Compared with HG-Exo group, mice in the HG-Exo+TLYSF group showed decreased levels of mALb, urinary NAG, Scr, and BUN. The podocyte membranes were relatively intact, and mitochondrial damage was alleviated. The positive rate of cells stained by the TUNEL decreased, along with a reduction in the optical density of NLRP3 and an increase in the optical density of WT-1. Furthermore, the mRNA expression levels of NLRP3, caspase-1, IL-1β, miR-200c-3p, and miR-148a-3p were all downregulated to varying degrees. The protein expression levels of NLRP3, ASC, caspase-1, and IL-1β also decreased. Conclusion Exosomes derived from GMC stimulated by high glucose can damage the kidneys of mice and induce podocyte pyroptosis. TLYSF may ameliorate podocyte pyroptosis by downregulating the expression of exosomal miR-200c-3p and miR-148a-3p and inhibiting the activation of the NLRP3/ASC/caspase-1 pathway.
Animals ; Exosomes/ultrastructure* ; Glucose/pharmacology* ; Male ; Podocytes/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred C57BL ; Mice ; Mesangial Cells/metabolism* ; Pyroptosis/drug effects* ; Rats ; MicroRNAs/genetics*

Thromboembolic disease seriously affects people's health, and even endangers life. Nattokinase(NK) is an alkaline serine protease with strong thrombolytic activity and low toxicity. However, when NK passes through the stomach, it is degraded by gastric acid and pepsin, and subsequently loses its thrombolytic activity. The application of preparation technology can form a protective layer and improve the high bioavailability of NK. This article briefly introduced the pharmacological properties of NK, and discussed the characteristic of different dosage forms. The development of NK preparation was prospected in order to promote its research and application.

Objective:To evaluate the association between long-term exposure to ambient ozone (O 3) and sperm quality. Methods:From January 1, 2014, to December 31, 2019, healthy sperm donors were recruited through the Human Sperm Bank of Shandong University Affiliated Reproductive Hospital. A total of 37 977 sperm donation data from 2 971 healthy volunteers were analyzed. The average annual O 3 concentration (0.01°× 0.01°) was matched according to household address. A multivariate mixed-effect model was used to analyze the exposure-response relationship between the average O 3 exposure concentration and sperm quality in the previous year, with each donor as a random intercept. All results were presented as % changes with 95% confidence intervals ( CIs) for all sperm parameters associated with 10 μg/m 3 increases in O 3. The effects of individual characteristics on the association between O 3 and sperm quality were evaluated by stratified analysis. Results:The average O 3 concentration in the year before semen collection was (107.09±7.50) μg/m 3. Each 10 μg/m 3 increase in O 3 was associated with declined sperm concentration (-3.12%, 95% CI:-4.55%, -1.67%), total sperm count (-5.21%, 95% CI:-7.28%, -3.09%), total sperm motility (-1.49%, 95% CI:-2.37%, -0.61%), progressive motility (-2.53%, 95% CI:-3.78%, -1.26%), total motile sperm count (-5.82%, 95% CI:-8.17%, -3.41%), and progressively motile sperm count (-6.22%, 95% CI:-8.73%, -3.64%). Men aged 30 and above, obese, and with lower education levels might be more susceptible to the influence of O 3 on sperm quality, but the difference was not statistically significant ( P>0.05). Conclusion:Long-term exposure to O 3 in Shandong Province is associated with a decrease in sperm quality.

Objective To establish an illness perception intervention program for patients with chronic obstructive pulmonary disease(COPD)and preliminarily analyse its application effect.Methods On the basis of systematic retrieval,a draft of the illness perception intervention program for patients with COPD was formed through content analysis.From May to August 2022,after 2 rounds of expert consultation,the illness perception intervention program for patients with COPD was formed.Patients with COPD who were hospitalized in the respiratory departments of 2 hospitals in Jiangsu Province from December 2022 to January 2023 were selected as the study subjects by convenience sampling method.The experimental group was treated with the illness perception intervention program,while the control group was treated with routine nursing.The effects of the 2 groups were compared by Brief Illness Perception Questionnaire,Modified British Medical Research Council、Brief Illness Perception Questionnaire、Acceptance and Action Questionnaire Ⅱ,COPD Assessment Test,COPD Self-management Scale before and after intervention,and a month after intervention.Results The illness perception intervention program for patients with COPD included 6 intervention topics and 24 specific intervention items.In the 2 rounds of correspondence,the expert group authority coefficient was 0.81,and the Kendall coordination coefficients were 0.19 and 0.16 in the second round(all P＜0.001).In the intervention study,the recruitment rate of patients was 56％;the withdrawal rate was 15％;and the high compliance rate was 80％.Repeated measures analysis of variance showed that there was an interaction effect between the scores of Acceptance and Action Questionnaire Ⅱ of the 2 groups(P＜0.05).The differences in the scores of Brief Illness Perception Questionnaire,COPD Assessment Test,Self-management Scale between the 2 groups were statistically significant in terms of time effect(P＜0.05),and the differences in the scores of the Brief Illness Perception Questionnaire and Acceptance and Action Questionnaire Ⅱ between the 2 groups were statistically significant in terms of main effect(P＜0.05).Conclusion The established illness perception intervention program for patients with COPD is scientific,feasible and effective,and it can provide practical references for clinical healthcare workers to promote illness perception and improve negative psychology in patients with COPD.

Objective To understand the current status of implicit theory derivation forms and applications in the health field at home and abroad,and to provide references for clinical practice and future research.Methods In accordance with the scoping review framework,PubMed,Embase,Web of Science,Cochrane Library,CINAHL,PsycINFO,CNKI,Wanfang,VIP,SinoMed were searched for relevant studies.The time limit for the search was from the establishment of the databases to 10 March 2024.Results A total of 45 articles were included in the study,including 24 articles on health behaviour and 21 articles on mental health,covering 14 derivations of implicit theories such as implicit health theory,implicit weight theory and implicit emotion theory.The main intervention process of implicit theories can be summarised as 3 major steps:belief-led intervention,attention examination and outcome testing.Conclusion The research value of implicit theory in the field of health has been gradually explored,and it is an important antecedent to improve individual health behaviors and mental health,and its brief and effective intervention model is more compatible with the characteristics of nursing work,so domestic and foreign nursing researchers can learn from the relevant research results to further optimize the strategies of health education,preventive guidance,and psychological care,and to carry out high-quality studies to validate them.

Objective:To investigate therapeutic effect of reinfusion of tumor-infiltrating lymphocyte(TIL)with clustered regularly interspaced short palindromic repeats/CRISPR-associated 9(CRISPR/CAS9)knockout programmed death-1(PD-1)on colon cancer in mice.Methods:Subcutaneous injection of CT26 was used to establish mouse colon cancer model.TIL was extracted from tumor tissue of three model mice,and peripheral blood lymphocytes were extracted.PD-1 gene was knocked out of TIL.Reinfusion experiments were divided into control group(Control),lymphocyte group(Lym),tumor-bearing mouse TIL group(TIL),lentivirus empty empty group(pVSV-G-PX458-NC)and PX458-PD-1-sgRNA1 group(PD-1-sgRNA1),with 10 mice in each group.Tumor tissue quality and tumor inhibition rate were detected in each group.TUNEL was used to detect cell apoptosis in tumor tissues of mice.ELISA was used to detect contents of TNF-α and IFN-γ in tumor tissues of mice.Immunohistochemistry was used to detect expressions of CD4+T and CD8+T cells in tumor tissue.Immunofluorescence was used to detect expressions of proliferating cell nuclear antigen-67(Ki-67)and vascular endothelial growth factor(VEGF).Western blot was used to detect expressions of PD-1 and its ligand PD-L1 in tumor tissues.Results:PD-1-sgRNA1 could significantly inhibit growth of mouse tumor cells in vivo,inhibit expressions of Ki-67 and VEGF in tumor tissues,as well as expressions of PD-1 and PD-L1,elevate apoptosis rate,contents of TNF-α and IFN-γ in tumor tissues,and expressions of CD4+T and CD8+T cells(all P<0.05).Conclusion:Reinfusion of TIL with CRISPR/CAS9 knockout PD-1 can significantly inhibit expressions of Ki-67 and VEGF in colon cancer mice,enhance infiltration of CD4+T and CD8+T cells,induce tumor cell apoptosis and inhibit tumor growth.

Objective To investigate the value of non-contrast CT(NCCT)-based radiomics for identifying acute unilateral middle cerebral artery occlusion(MCAO)with negative hyperdense artery sign(HAS).Methods All 80 patients with acute unilateral MCAO confirmed by angiography(MR angiography[MRA]or CT angiography[CTA]or DSA)and presenting with negative NCCT presentation for HAS were enrolled from January 2015 to June 2023 in the Emergency Department of Stroke Center of Affiliated Hospital of Yangzhou university.On the NCCT images,the occluded segment of the middle cerebral artery on the affected side of each case and the corresponding segment of the vessel on the normal side were used as the regions of interest,and a total of 108 radiomic features were extracted.The least absolute shrinkage and selection operator(LASSO)was used to screen the key features,construct and calculate the radiomics score,and four imaging histology models,support vector machine(SVM),light gradient boosting machine(LightGBM),GradientBoosting and adaptive boosting(AdaBoost),were built respectively to predict MCAO.Predictive performance was evaluated by the area under the receiver operating characteristic curves,and comparisons between the modeled receiver operating characteristic curves were made using the Delong test.Finally,the value of the application of radiological modeling was assessed by clinical decision curve analysis(DCA).Results The NCCT images based on 160 vessels were finally screened for 6 key features,including skewness,energy,gray level size zone matrix(GLSZM)-gray uneven,GLSZM-low gray area emphasis,GLSZM-size area non-uniform standardization,GLSZM-area entropy.The area under the curve(AUC)of the SVM-test was 0.688(95％CI 0.497-0.878)with an accuracy of 0.688;the AUC of the LightGBM-test was 0.787(95％CI 0.620-0.955)with an accuracy of 0.781;the AUC of the GradientBoosting-test was 0.654(95％CI 0.457-0.852)with an accuracy of 0.688;the AUC of the AdaBoost-test was 0.707(95％CI 0.515-0.899)with an accuracy of 0.750.The Delong test showed a statistically significant difference between LightGBM-test and GradientBoosting-test(P=0.040),and no statistically significant difference in performance between the remaining models(all P＞0.05).DCA showed that the LightGBM-test performed better.Conclusion NCCT-based radiomics has good diagnostic efficacy for identifying acute unilateral MCAO with negative HAS,and this conclusion needs to be further verified by multi-center and large sample studies.

Objective:To evaluate the association between long-term exposure to ambient ozone (O 3) and sperm quality. Methods:From January 1, 2014, to December 31, 2019, healthy sperm donors were recruited through the Human Sperm Bank of Shandong University Affiliated Reproductive Hospital. A total of 37 977 sperm donation data from 2 971 healthy volunteers were analyzed. The average annual O 3 concentration (0.01°× 0.01°) was matched according to household address. A multivariate mixed-effect model was used to analyze the exposure-response relationship between the average O 3 exposure concentration and sperm quality in the previous year, with each donor as a random intercept. All results were presented as % changes with 95% confidence intervals ( CIs) for all sperm parameters associated with 10 μg/m 3 increases in O 3. The effects of individual characteristics on the association between O 3 and sperm quality were evaluated by stratified analysis. Results:The average O 3 concentration in the year before semen collection was (107.09±7.50) μg/m 3. Each 10 μg/m 3 increase in O 3 was associated with declined sperm concentration (-3.12%, 95% CI:-4.55%, -1.67%), total sperm count (-5.21%, 95% CI:-7.28%, -3.09%), total sperm motility (-1.49%, 95% CI:-2.37%, -0.61%), progressive motility (-2.53%, 95% CI:-3.78%, -1.26%), total motile sperm count (-5.82%, 95% CI:-8.17%, -3.41%), and progressively motile sperm count (-6.22%, 95% CI:-8.73%, -3.64%). Men aged 30 and above, obese, and with lower education levels might be more susceptible to the influence of O 3 on sperm quality, but the difference was not statistically significant ( P>0.05). Conclusion:Long-term exposure to O 3 in Shandong Province is associated with a decrease in sperm quality.

OBJECTIVE: To explore clinical rules based on the big data of the emergency department of the Second Affiliated Hospital of Guangzhou Medical University, and to establish an integrated platform for clinical research in emergency, which was finally applied to clinical practice. METHODS: Based on the hospital information system (HIS), laboratory information system (LIS), emergency specialty system, picture archiving and communication systems (PACS) and electronic medical record system of the Second Affiliated Hospital of Guangzhou Medical University, the structural and unstructured information of patients in the emergency department from March 2019 to April 2022 was extracted. By means of extraction and fusion, normalization and desensitization quality control, the database was established. In addition, data were extracted from the database for adult patients with pre screening triage level III and below who underwent emergency visits from March 2019 to April 2022, such as demographic characteristics, vital signs during pre screening triage, diagnosis and treatment characteristics, diagnosis and grading, time indicators, and outcome indicators, independent risk factors for poor prognosis in patients were analyzed. RESULTS: (1) The data of 338 681 patients in the emergency department of the Second Affiliated Hospital of Guangzhou Medical University from March 2019 to April 2022 were extracted, including 15 modules, such as demographic information, triage information, visit information, green pass and rescue information, diagnosis information, medical record information, laboratory examination overview, laboratory information, examination information, microbiological information, medication information, treatment information, hospitalization information, chest pain management and stroke management. The database ensured data visualization and operability. (2) Total 140 868 patients with pre-examination and triage level III and below were recruited from the emergency department database. The gender, age, type of admission to the hospital, pulse, blood pressure, Glasgow coma scale (GCS) and other indicators of the patients were included. Taking emergency admission to operating room, emergency admission to intervention room, emergency admission to intensive care unit (ICU) or emergency death as poor prognosis, the poor prognosis prediction model for patients with pre-examination and triage level III and below was constructed. The receiver operator characteristic curve and forest map results showed that the model had good predictive efficiency and could be used in clinical practice to reduce the risk of insufficient emergency pre-examination and triage. CONCLUSIONS The establishment of high-quality clinical database based on big data in emergency department is conducive to mining the clinical value of big data, assisting clinical decision-making, and improving the quality of clinical diagnosis and treatment.
Adult ; Humans ; Big Data ; Emergency Service, Hospital ; Triage/methods* ; Intensive Care Units ; Hospitalization ; Retrospective Studies

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr⁹⁹⁰ to enhance its activity. Mutation of SERCA2-Tyr⁹⁹⁰ disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca²⁺_ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca²⁺_ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr⁹⁹⁰ in HCC.