Objective:To investigate the effects and mechanisms of angiotensin-converting enzyme 2 (ACE2) and Captopril (CAP) on mechanical ventilation-induced lung injury (VILI) in mice.Methods:Seventy-two healthy male BALB/c mice were randomly assigned (using a random number table) into six groups ( n=12 per group): normal control (NC) group, VILI group, ACE2 group, VILI+ACE2 group, CAP group, and VILI+CAP group. One hour prior to mechanical ventilation, the ACE2 and VILI+ACE2 groups were intraperitoneally injected with ACE2 at a dose of 0.1 mg/kg, while the CAP and VILI+CAP groups were intraperitoneally injected with CAP at a dose of 2.5 mg/kg. Following mechanical ventilation, serum samples were collected and enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory factors [platelet activating factor (PAF), endothelin-1 (ET-1), soluble intercellular adhesion molecule-1 (sICAM-1), prostaglandin E2 (PGE2)] and cardiovascular system related indicators [von Willebrand factor (vWF), thrombomodulin (TM), angiotensin (Ang) (1-9), Ang (1-7), prostacyclin I 2 (PGI2)]. Bronchoalveolar lavage fluid (BALF) was gathered, and total protein concentration was determined using BCA method, and sICAM-1 levels were measured by ELISA. Lung tissues were collected and subjected to hematoxylin and eosin staining (HE staining) for the assessment of pathological lung injury and lung injury scoring. Western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were utilized to detect the relative expression levels of ACE2 protein and mRNA, respectively. Statistical analysis was performed using IBM SPSS 20.0 software. Intergroup comparisons were conducted using one-way analysis of variance followed by the least significant difference (LSD) test. Results:No statistically significant differences were observed in the levels of PAF, ET-1, sICAM-1, vWF, TM, Ang(1-9), Ang(1-7), and PGI2 in serum and lung tissues between the ACE2/CAP groups and the NC group (all P>0.05). Compared with the VILI group, the VILI+ACE2 and VILI+CAP groups exhibited significantly decreased serum and lung tissue levels of PAF, ET-1, sICAM-1, and vWF (all P<0.05), while the levels of TM, Ang(1-9), Ang(1-7), and PGI2 were significantly increased (all P<0.05). Pathological lung injury was alleviated, and the lung wet/dry weight ratio was significantly reduced (all P<0.05) in the VILI+ACE2 and VILI+CAP groups. Furthermore, both ACE2 protein and mRNA expression levels were significantly increased in these groups (all P<0.05). Conclusion:Both ACE2 and CAP can inhibit inflammation and protect the cardiovascular system, possibly by promoting the ACE2/Ang(1-9)/Ang(1-7) axis, thereby exerting a protective effect against VILI.

Astragali Radix (AR) and Notoginseng Radix et Rhizoma (NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair (AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction (TAC) in mice and angiotensin II (Ang II)-induced neonatal rat cardiomyocytes (NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (CTn-T), and interleukin-6 (IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes (ANP, BNP, and MYH7) in vivo and in vitro. Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators (COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog 3 (Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein (Drp1) (Ser616) expression and upregulated mitogen 2 (MFN-2) and optic atrophy 1 (OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Myocytes, Cardiac/metabolism* ; Mice ; Rats ; Male ; Mitochondrial Dynamics/drug effects* ; Ventricular Remodeling/drug effects* ; Astragalus Plant/chemistry* ; Mice, Inbred C57BL ; Rhizome/chemistry* ; Panax notoginseng/chemistry* ; Rats, Sprague-Dawley ; Natriuretic Peptide, Brain/genetics* ; Humans ; Angiotensin II ; Astragalus propinquus

Background and objective Lung cancer is the cancer with the highest incidence and mortality rates in China,and non-small cell lung cancer(NSCLC)accounts for 80％-85％of all malignant lung tumors.Currently,surgical treat-ment remains the primary treatment modality for lung cancer.In recent years,the effectiveness of immune checkpoint inhibi-tors for NSCLC has become a consensus,and neoadjuvant immunochemotherapy(nICT)has shown promising efficacy and safety in early to intermediate stage NSCLC.However,there are fewer studies related to nICT for locally advanced NSCLC.This study aims to evaluate the efficacy and safety of nICT therapy in locally advanced resectable NSCLC.Methods 85 con-firmed resectable stage ⅢA and ⅢB patients treated in the Department of Thoracic Surgery,Second Hospital of Lanzhou University,from January 2021 to April 2024,were divided into the nICT group(n=32)and the surgery alone group(n=53).Clinical baseline data,perioperative indicators,postoperative complications,imaging response rate,pathological response rate,incidence of adverse events,and quality of life were compared between the two groups.Results There were no statisti-cally significant differences in clinical baseline data between the two groups(P＞0.05).Incidence of choosing thoracotomy was higher in the nICT group than in the surgery alone group(P=0.002).There were no significant differences in surgical time,intraoperative blood loss,number of dissected lymph nodes,duration of chest tube placement,postoperative hospital stay,and R0 resection rate between the two groups(P＞0.05).The overall incidence of postoperative complications was 31.25％in the nICT group and 22.64％in the surgery alone group,with no statistically significant difference(P=0.380).In the nICT group,the objective response rate(ORR)was 84.38％,with 5 cases of complete response(CR)(15.63％),22 cases of partial response(PR)(68.75％),15 cases of pathological response rate(pCR)(46.88％),and 11 cases of major pathological reaponse(MPR)(34.38％).During nICT treatment,12 cases(37.50％)experienced grade 3 treatment-related adverse events,no death induced by adverse events or immune related adverse events.Moreover,the symptoms of the patients were improved after nICT treat-ment.Conclusion Neoadjuvant immunochemotherapy shows promising efficacy in locally advanced resectable NSCLC,with manageable treatment-related adverse events.It is a safe and feasible neoadjuvant treatment modality for locally advanced resectable NSCLC.

Objective:To discuss the effect of bone marrow mesenchymal stem cells(BMSCs)-derived exosomes(Exo)on isoproterenol(ISO)-induced myocardial fibrosis in the rats,and to clarify its mechanism.Methods:The Exo was isolated from the BMSCs and characterized by transmission electron microscope,nanoparticle tracking analysis,and Western blotting methods.Forty SD rats were divided into control group,model group,BMSCs-Exo group,and BMSCs-Exo+ferroptosis activator(Erastin)group,and there were 10 rats in each group.The myocardial fibrosis models were established by subcutaneous injection of ISO in all the rats except control group.The rats in BMSCs-Exo and BMSCs-Exo+Erastin groups were given BMSCs-Exo,and the rats in BMSCs-Exo+Erastin group were additionally injected with Erastin intraperitoneally.After 4 weeks,echocardiography was used to detect the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end diastolic diameter(LVEDD),and left ventricular end systolic diameter(LVESD)of the rats in various groups;HE staining was used to observe the pathomorphology of myocardium tissue of the rats in various groups;Masson staining was used to observe the fibrosis degrees of myocardium tissue of the rats in various groups;immunohistochemistry was used to detect the positive expression rates of α-smooth muscle actin(α-SMA),type Ⅰ collagen(COL-Ⅰ),and type Ⅲ collagen(COL-Ⅲ)in myocardium tissue of the rats in various groups;colorimetry was used to detect the Fe2+level in myocardium tissue of the rats in various groups;Western blotting method was used to detect the expression levels of acyl-CoA synthetase long chain family member 4(ACSL4),ferritin heavy chain 1(FTH1),glutathione peroxidase 4(GPX4),and solute carrier family 7 member 11(SLC7A11)proteins in myocardium tissue of the rats in various groups.Results:The particles isolated from BMSCs had a typical lipid bilayer structure,and most particle sizes distributed around 100 nm.High expression levels of CD63,CD9,tumor susceptibility gene 101(TSG101),and heat shock protein 70(HSP70)proteins confirmed the particles as Exo.Compared with control group,the LVEF and LVFS of the rats in model group were significantly decreased(P＜0.05),LVEDD and LVESD were increased(P＜0.05),the myocardial cell arrangement was disordered,some nuclear shrinkage and necrosis were seen,the collagen volume fraction(CVF)was significantly increased(P＜0.05),the positive expression rates of α-SMA,COL-Ⅰ,and COL-Ⅲ were significantly increased(P＜0.05),the Fe2+level in myocardium tissue was significantly increased(P＜0.05),the expression level of ACSL4 protein was significantly increased(P＜0.05),and the expression levels of FTH1,GPX4,and SLC7A11 proteins were significantly decreased(P＜0.05).Compared with model group,the LVEF and LVFS of the rats in BMSCs-Exo group were significantly increased(P＜0.05),the LVEDD and LVESD were significantly decreased(P＜0.05),the myocardial tissue damage was significantly alleviated,the CVF was significantly decreased(P＜0.05),the positive expression rates of α-SMA,COL-Ⅰ,and COL-Ⅲ were significantly decreased(P＜0.05),the Fe2+level in myocardium tissue was significantly decreased(P＜0.05),the expression level of ACSL4 protein was significantly decreased(P＜0.05),and the expression levels of FTH1,GPX4,and SLC7A11 proteins were significantly increased(P＜0.05).Compared with BMSCs-Exo group,the LVEF and LVFS of the rats in BMSCs-Exo+Erastin group were significantly decreased(P＜0.05),the LVEDD and LVESD were significantly increased(P＜0.05),the myocardial cell edema and necrosis were seen,the CVF was significantly increased(P＜0.05),the positive expression rates of α-SMA,COL-Ⅰ,and COL-Ⅲ were significantly increased(P＜0.05),the Fe2+level in myocardium tissue was significantly increased(P＜0.05),the expression level of ACSL4 protein was significantly increased(P＜0.05),and the expression levels of FTH1,GPX4,and SLC7A11 proteins were significantly decreased(P＜0.05).Conclusion:BMSC-derived Exo can improve the myocardial fibrosis in the rats induced by ISO,and its mechanism may be related to the inhibition of ferroptosis.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium. Currently, treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia. However, these modalities are unsatisfactory in achieving the desired therapeutic outcomes. Halofuginone hydrobromide (HF), an herbal active ingredient, has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation. However, HF's medical efficacy is limited due to its poor water solubility, short half-life (t _1/2), and non-target toxicity. In the current study, by using the advantages of nanotechnology, we presented a novel dual-targeted nanocomplex, termed HA-M@P@HF NPs, which consisted of a hyaluronic acid (HA)-modified hybrid membrane (M)-camouflaged poly lactic-co-glycolic acid (PLGA) nanosystem for HF delivery. These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA (HFLS-RA). In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia, safeguarding against bone destruction in rats with adjuvant-induced arthritis (AIA). Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA, thereby offering a promising therapeutic strategy for RA.

Objective:To investigate the impact of pumpkin polysaccharide(PP)on hypoxia/reoxygenation(H/R)-induced myocardial cell(H9C2)injury by regulating Nrf2/γ-GCS pathway.Methods:HR cell models were established,and the concentration of pumpkin polysaccharide(PP)was determined.H9C2 cells were grouped into Control group,H/R group,pumpkin polysaccharide group(PP group,2 mg/L PP),Nrf2 inhibitor group(ML385 group,2.0 μmol/L ML385),and PP+ML385 group(2.0 mg/L PP+2.0 μmol/L ML385),the apoptosis,mitochondrial membrane potential changes,oxidative stress(LDH,MDA,SOD,ROS),the lev-els of inflammatory factors(TNF-α,IL-6,IL-1β)and the protein expressions of Nrf2 and γ-GCS in H9C2 cells were detected,respec-tively.Results:Compared with Control group,H/R group had changes in cell morphology,the cell injury and mitochondrial membrane potential decreased,the H9C2 cell viability,SOD and protein expression levels of Nrf2 and γ-GCS were significantly decreased,while the apoptosis rate,LDH,MDA,ROS,and levels of TNF-α,IL-6 and IL-1β were significantly increased(P<0.05);compared with H/R group,the cell injury in PP group was reduced,the mitochondrial membrane potential was restored,the H9C2 cell viability,SOD and protein expression levels of Nrf2 and γ-GCS were significantly increased,and the apoptosis rate,LDH,MDA,ROS,and levels of TNF-α,IL-6 and IL-1β were significantly decreased(P<0.05),the effect of ML385 was opposite to that of PP,and ML385 could reverse the antioxidant and anti-inflammatory effects of PP.Conclusion:PP up-regulates the Nrf2/γ-GCS pathway to exert antiox-idant and anti-inflammatory effects,and reduces H/R-induced H9C2 cell injury.

Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflam-mation or inhibiting synovial hyperplasia.However,these modalities are unsatisfactory in achieving the desired therapeutic outcomes.Halofuginone hydrobromide(HF),an herbal active ingredient,has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation.However,HF's medical efficacy is limited due to its poor water solubility,short half-life(ti/2),and non-target toxicity.In the current study,by using the advantages of nanotechnology,we presented a novel dual-targeted nanocomplex,termed HA-M@P@HF NPs,which consisted of a hyaluronic acid(HA)-modified hybrid membrane(M)-camouflaged poly lactic-co-glycolic acid(PLGA)nanosystem for HF delivery.These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA(HFLS-RA).In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflam-mation and synovial hyperplasia,safeguarding against bone destruction in rats with adjuvant-induced arthritis(AIA).Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA,thereby offering a promising therapeutic strategy for RA.

Objective    To investigate the relationship between DDX46 genes and invasion and migration of esophageal squamous cell carcinoma cells. Methods    Human esophageal squamous cell carcinoma cells TE-1 were transfected by fluorescent marker shRNA lentivirus (shDDX46 group), and an empty vector was transfected as a control (shCtrl group). The expression rate of green fluorescent protein under the microscope was used to evaluate the cell transfection efficiency. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blotting (WB) detected the knockdown efficiency of the target gene at the mRNA and protein expression levels. Wound healing, invasion assay and migration assay detected the changes of invasion and metastasis ability. Classical pathway analysis was used to explore signaling pathway changes and the possible mechanism of DDX46 in the invasion and metastasis was explored by detecting fibronectin expression. Results    DDX46 gene at mRNA and protein levels was significantly inhibited after lentiviral transfection. Wound healing showed that after 8 h the cell mobility of TE-1 cells decreased significantly (P=0.001). Invasion assay showed that after 24 h the average cell metastasis rate of TE-1 cells was lower in the shDDX46 group than that in the shCtrl group (P<0.001). The cell metastasis rate in the shDDX46 group corresponding to observation points in the transwell assay was lower than that in the shCtrl group (P<0.001) after 24 h culture. The results of the classical pathway analysis showed that the integrin signaling pathway activity was inhibited, further exploration of the mechanism of action found that the expression of fibronectin associated with cell adhesion was decreased. Conclusion    DDX46 gene is related to the invasion and migration ability of esophageal squamous cell carcinoma cells. Knockdown of DDX46 genes may reduce cell adhesion by downregulating the integrin pathway signaling.

This article firstly reviews the current application status of mobile health based on social networking media, mobile health applications, wearable devices in infertility patients′nursing. Then, this paper analyzes the application effects of mobile health in the five aspects of treatment process management, health education, medication management, lifestyle management and psychological care for infertility patients based on the literature. The existing problems are analyzed and prospected on this basis, in order to provide a reference for the application of mobile health to infertility patients′nursing in China.

Objective:To explore the occurrence and influencing factors of perimenopausal syndrome among Han, Hui and Tibetan women in Gansu Province.Methods:A stratified cluster sampling method was used to select 7290 women aged 40-55 years as the research subjects for cross-sectional survey. The questionnaire was used to investigate demographic characteristics, marriage and childbearing menstrual history, and the modified Kupperman score was used to investigate the symptoms related to perimenopausal syndrome. The data were statistically analyzed using SPSS20.0 software.Results:The natural menopausal age of women in Gansu Province was (47.43±3.99) years old, Hui women had the earliest age of menopause (47.08±4.29). There were statistically significant differences in occupation, education level and residence among the three ethnic groups ( P<0.001, P=0.001, P=0.005). The incidence of perimenopausal syndrome was 58.85% (246/418) for Hui, 44.16% (136/308) for Tibetans, and 41.06% (2695/6564) for Hans. The incidence of perimenopausal syndrome and the grade of related symptoms were significantly different among the three ethnic groups (all P<0.001). Han women had the highest proportion of mild symptoms, while Hui women and Tibetan women had the highest proportion of moderate symptoms. The differences of the incidence of mild and severe symptoms among the three ethnic groups were statistically significant (all P<0.001). Logistic regression analysis showed that engaging in heavy physical labor is a common risk factor for the incidence of perimenopausal syndrome in the three ethnic groups. Conclusion:The prevention and treatment of perimenopausal syndrome can be carried out from the following aspects: promoting economic development, improving living conditions, changing life and work patterns, increasing investment in education, medical and health care, and strengthening knowledge popularization.