ObjectiveTo explore the role of lead exposure in the phenotypic transformation of vascular smooth muscle cells (VSMC), and to provide new insights for the mechanism of lead impact on vascular lesions. MethodsMouse aortic smooth muscle cells (MOVAS) were divided into a control group (0 μmol·L^-1), low concentration lead groups (0.1, 1, 5, and 10 μmol·L^-1), and high concentration lead groups (15, 25, and50 μmol·L^-1). MTT assays were used to assess the proliferation of the cells, and scratch assays were implicated to measure migration ability of the cells. Fluorescence quantitative PCR was employed to determine levels of mRNA expression for smooth muscle actin α (α⁃SMA), smooth muscle 22 alpha (SM22α), synthetic phenotype-related genes osteopontin (OPN), matrix metalloproteinase 9 (MMP9), and the transcription factor SOX9. Immunoblotting was used to determine levels of protein expression for α-SMA, OPN, and MMP9. ResultsProliferation of MOVAS was observed under the lead ions concentrations of 0‒50 µmol·L^-1, with a significant increase of proliferation compared to the control group at the concentrations of 5‒50 µmol·L^-1 (all P<0.05). The migration ability of cells gradually increased at the concentrations of 0‒10 µmol·L^-1, with a significant increase at 5 (q=4.574, P=0.003) and 10 µmol·L^-1 (q=10.570, P<0.001) compared to the control group. The 10 µmol·L^-1 lead ions significantly reduced the levels of mRNA expression for vascular smooth muscle contractile phenotype genes α⁃SMA (q=7.426, P<0.001) and SM22α (q=4.766, P=0.001), while significantly increasing the levels of mRNA expression for OPN (q=11.330, P<0.001), MMP9 (q=7.842, P<0.001), and SOX9 (q=11.120, P<0.001) genes. Furthermore, the 10 µmol·L^-1 lead ions significantly reduced the levels of protein expression for the vascular smooth muscle contractile phenotype marker α-SMA protein (q=2.897, P=0.049), while significantly increasing the levels of protein expression for the synthetic markers OPN (q=3.188, P=0.031) and MMP9 (q=3.292, P=0.026), compared to the control group. ConclusionTreatment with lead in vitro induced VSMC to differentiate from contractile phenotype to synthetic phenotype, indicating that a certain dose of lead exposure might be detrimental to the cardiovascular system.

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Objective To explore the repair effect and mechanism of human amniotic mesenchymal stem cells(hAMSCs)on endometrial injury.Methods hAMSCs were isolated using a two-enzyme digestion and then cultured.The third-passage(P3)cells were harvested to detect the surface markers by flow cytometry and to identify their trilineage differentiation potentials.Eighteen nulliparous female SD rats(8～9 weeks old,weighing 250～280 g)were randomly divided into 3 groups(n=6):normal control group,model group,and hAMSCs group.A rat model of intrauterine adhesions(IUA)was established in SD rats by using curettage combined with lipopolysaccharide(LPS)infection.In 2 weeks after modeling,the hAMSCs group received a bilateral uterine horn transplantation of 0.2 mL hAMSCs(1.0×10? cells/mL),while the model group received a same volume of PBS into both uterine horns.All rats were sacrificed in 2 weeks after transplantation.HE and Masson staining was used to observe endometrial thickness and gland number as well as endometrial fibrosis area.RT-qPCR and Western blotting were performed to detect the mRNA and protein levels of TGF-β1,Smad3,Smad7,epithelial-mesenchymal transition(EMT)markers(E-cadherin,Vimentin),fibrosis factor α-SMA,and endometrial estrogen receptor(ER)and progesterone receptor(PR)in endometrial tissues.Results The obtained cells were identified as hAMSCs due to the characteristics of surface markers and differentiation potentials.Compared with the normal control group,the model group showed decreased endometrial thickness,reduced gland number,increased fibrosis area,and enhanced mRNA and protein levels of fibrosis-related factors TGF-β1,Smad3,Vimentin,and α-SMA(P<0.01),while down-regulation of fibrosis-inhibiting molecule Smad7,the EMT marker E-cadherin,and endometrial receptors ER and PR at both mRNA and protein levels(P<0.01).hAMSCs transplantation increased endometrial thickness and gland number,decreased fibrosis area,and down-regulated mRNA expression of the aforementioned fibrosis-related factors(P<0.01),and up-regulated the mRNA expression levels of Smad7,E-cadherin,ER,and PR(P<0.01).The hAMSCs group also exhibited obviously down-regulated protein levels of TGF-β1,Smad3,and α-SMA(P<0.05),while enhanced protein levels of Smad7 and PR(P<0.05).Conclusion Intrauterine transplantation of hAMSCs can promote the repair of endometrial injury,and inhibits endometrial EMT and fibrosis through the TGF-β1/Smad7 signaling pathway.

Objective:The components of Rubus parvifolius L. were analyzed based on UPLC-MS/MS technology and combined with network pharmacology analysis to explore the mechanism of action of Rubi Parvifolii Radix in treating inflammation, cough, fever, influenza and sore throat. Method:The chemical constituents of Rubi Parvifolii Radix were identified according to the information of mass spectrometry. The network pharmacology was used to analyze the corresponding targets and related pathways of its chemical components, and the "component-target-pathway" interaction diagram was drawn. PyMOL 2.5.7 software wasused to perform molecular docking between active components and key targets.Results:Twenty chemical components were identified by UPLC-MS/MS, and 15 components were screened out by network pharmacology, which can be used as quality markers of Rubi Parvifolii Radix, namely Azelaic acid, Procyanidol B3, Caprolactam, Bis (2-ethylhexyl) adipate, Cryptochlorogenic acid, 3-O-Feruloylquinic, Ellagic acid, Aurantiamide acetate, 2 α,3 β,19 α,23-Tetrahydroxyurs-12-en-28-oic acid, L-Epicatechin, (E)-3-Indoleacrylic acid, Euscaphic acid, Suberic acid, Diisononyl phthalate and Prodelphinidin T4. Molecular docking showed that 5 compounds compared with the reference substance could bind to the target proteins of disease well. Conclusions:The 15 active ingredients in Rubi Parvifolii Radix, including Caprolactam and (E)-3-Indoleacrylic acid, may play a therapeutic role in treating colds, high fever, sore throat, and inflammation by acting on targets such as AKT1 and TNF. This provides a certain reference for the clinical application of Rubi Parvifolii Radix.

Objective:To conduct a series case study on hospitalized anthrax cases in five hospitals in North China, to share clinical experiences in the diagnosis and treatment of cutaneous and pulmonary anthrax.Methods:A retrospective, multicenter cohort study was conducted on the anthrax patients admitted to five hospitals in North China from August 2018 to March 2022. Forty patients were divided into severe and mild groups. The clinical features, treatment and prognosis of the patients were collected and analysed. Statistical evaluations included independent sample t test, Mann-Whitney U test, and chi-square test. Results:Among the 40 patients with anthrax, 10(25.0%) were severely ill and 30(75.0%) were mildly ill. According to the sites of infection, 40 patients were classified as 39 cutaneous anthrax cases (one case had secondary pulmonary anthrax) and one pulmonary anthrax case. The rates of chills and fever, lymphadenopathy, liver dysfunction and hypoalbuminemia in the severe group were all higher than those in the mild group, with statistically significant differences ( χ2=5.71, 6.54, 4.68 and 9.22, respectively, all P<0.05). The peripheral white blood cell count, neutrophil count, neutrophil/lymphocyte ratio and C-reactive protein were (11.8±4.9)×10 9/L, (9.5±5.1)×10 9/L, 8.6±7.3, 27.9(8.6, 167.7) mg/L, respectively, which were all higher than those in mild disease group ((7.5±2.4)×10 9/L, (5.0±2.1)×10 9/L, 3.2±2.3, 3.5(1.2, 14.7) mg/L), with statistically significant differences ( t=2.66, t=2.71, t=2.32 and Z=-3.01, respectively, all P<0.05). The albumin level in the severe group was (35.5±8.1) g/L, which was lower than that of the mild group ((43.7±3.2) g/L), and the difference was statistically significant ( t=-3.13, P=0.011). The severe cases were more likely to have skin lesions greater than four centimetre in diameter, multiple, vesicular, or edematous, with a significant difference ( χ2=6.01, P=0.014). Among 39 patients with cutaneous anthrax, 28(71.8%) in the mild group were treated with penicillin alone, and nine (23.1%) in the severe group were treated with penicillin, ofloxacin, piperacillin/tazobactam combined with one of linezolid, doxycycline, or clindamycin for anti-infection treatment. The two patients with pulmonary anthrax were treated with closed thoracic drainage for pleural effusion and pneumothorax, and were treated with two bactericidal and one protein synthesis inhibitor antibiotics. All 40 anthrax patients were cured and discharged from hospital. Conclusions:Patients with mild cutaneous anthrax can generally be treated with single penicillin, and patients with severe cutaneous anthrax and pulmonary anthrax should be treated with combined antibiotics.

Objective:To investigate the survival of cancer cases diagnosed during 2002-2013 in Shanghai. Methods:Data on new cancer cases with dead and follow-up information were obtained from the population-based cancer registry and vital statistics system of Shanghai Municipal Center for Disease Control and Prevention.Survival indicators stratified by year of diagnosis,gender,site and age were analyzed.Number of cases and proportion were calculated.The observed survival rates were calculated based on the life table.The probabilities of surviving from 0 to 99 years old were estimated according to the Elandt-Johnson model,and then the cumulative expected survival rates were calculated according to the Ederer Ⅱ method.Finally,the relative survival rates and average annual percent changes of their trends were calculated.The age-standardized relative survival rates adjusted by International Cancer Survival Standard weights were calculated. Results:Total 644 520 new cancer cases were diagnosed during 2002-2013 in Shanghai,accounting for 643 545(99.85％)cases included in the observed cohort for survival analysis.The 5-year observed survival rate increased from 37.61％to 46.47％.The 5-year relative survival rate increased from 42.1 8％to 51.11％.The 5-year age-standardized relative survival rate increased from 40.57％to 49.80％.Among the 5-year relative survival rates of cases diagnosed during 2011 to 2013,99.43％of thyroid cancer was the highest,followed by female breast cancer(88.35％)and corpus uteri cancer(85.56％);5.87％of pancreas cancer was the lowest,followed by gallbladder cancer(13.64％)and oesophagus cancer(17.72％).the rate of lung cancer with the largest number of cases was 23.59％,followed by colorectal cancer(59.82％)and stomach cancer(38.65％).The 5-year relative survival rate of total cases of all sites increased from 40.55％in 2002 to 52.77％in 2013,with an average annual percent change of 2.40％.13 cancer types showed increasing trends,such as liver cancer and lung cancer,while the trends of other cancer types were not statistically significant,such as pancreatic cancer and gallbladder cancer. Conclusion:The diagnostic levels and survival rates of cancer cases have been improved continuously in Shanghai.The trends of different cancer types were varied.

Objective:To develop a learning scale of scientific methods for medical students and to evaluate the reliability and validity of the scale.Methods:Based on the principles of planned behavior theory, the original scale was developed through literature analysis, pre-interview and experts' consultation. A preliminary survey was conducted among 105 medical undergraduates with random cluster sampling, and the primary scale was formed by exploratory factor analysis. Then, 851 undergraduates were selected as the objects of formal survey, and the formal scale was finally determined by the reliability and validity evaluation and confirmatory factor analysis. SPSS 22.0 and AMOS 22.0 softwares were used for statistical analysis of the measurement data.Results:The formal scale was composed of 5 latent variables, 9 observed variables and 51 items. The overall Cronbach’s α coefficient and the overall retest reliability were 0.97 and 0.89, respectively. Composite reliability and KMO values of each latent variable were more than 0.80, and the values of average variance extraction were over 0.50. The fitness test ( P=0.155) showed acceptable fitting quality with the main fit indices of χ2/ df=1.41, RMR=0.04, RMSEA=0.02, etc. Conclusion:The learning scale of scientific methods shows satisfactory reliability, validity and fitness, which can be applied as a measuring tool to evaluate the learning behavior of scientific methods for medical students.

Humans ; Female ; Prevalence ; Breast Neoplasms ; Cancer Survivors ; Non-alcoholic Fatty Liver Disease ; Liver

Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn²⁺ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn²⁺, we constructed a TDN-MnO₂ complex and found that it displayed a much higher efficacy than TDN plus Mn²⁺ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO₂. These findings provide new therapeutic opportunities for cancer therapy.