This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Objective:To understand the loss to follow-up of children born to pregnant women with HIV infection (HIV-exposed children) and analyze its influencing factors in China in 2019.Methods:The data were collected from the follow-up records of pregnant women with HIV infection and their children reported by the national "Management Information System for the Prevention of HIV, syphilis and Hepatitis B Mother-to-Child Transmission" in 2019. HIV-exposed children were defined as those who were not followed up after birth or who were not followed up at 18 months of age and who were not followed up at 21 months of age. The univariate and multivariate influencing factors of loss to follow-up of children born to HIV-infected pregnant women were analyzed by χ2 test and logistic regression model. SPSS 25.0 software was used for statistical analysis. Results:The number of HIV-infected pregnant women was 5 039, the number of live-born children was 5 035, the number of loss to follow-up children within 18 months of age was 283, and the loss to follow-up rate children was 5.62%(283/5 035). The results of multivariate logistic regression analysis showed that the rate of loss to follow-up of exposed children born to pregnant women who worked as farmers (animal husbandry and fishery) (a OR=0.34, 95% CI: 0.22-0.53), unmarried (a OR=0.47, 95% CI: 0.24-0.93), first marriage (a OR=0.38, 95% CI: 0.22-0.67), remarriage (a OR=0.36, 95% CI: 0.20-0.67) and cohabiting (a OR=0.47, 95% CI: 0.23-0.97), and knew they had HIV infection before this pregnancy (a OR=0.53, 95% CI: 0.40-0.70) was lower. Han nationality (a OR=1.52, 95% CI: 1.09-2.13), primary school (a OR=2.06, 95% CI: 1.10-3.89) and junior middle school (a OR=1.81, 95% CI: 1.03-3.17) educational level, non-use of antiviral drugs (a OR=6.21, 95% CI: 4.32-8.93) and delivery in township (street) level midwifery institutions (a OR=5.72, 95% CI: 1.61-20.27) had higher rates of loss to follow-up among infants born to HIV-infected pregnant women. Conclusions:HIV-exposed children still have a specific rate of loss to follow-up in China in 2019. In order to further reduce the rate of loss to follow-up, it is of great significance to improve the detection rate of HIV before pregnancy and the rate of antiviral drugs used in pregnant women with HIV infection, which is of great significance for the effective implementation of comprehensive intervention measures of prevention of mother-to-child transmission of HIV.

Objective To explore the incidence and risk factors of perioperative ischemic stroke in non-cardiac and non-neurosurgical surgeries and its correlation with preoperative risk assessment of cerebrovascular events,so as to guide perioperative risk management.Methods A retrospective study was conducted on 40 patients aged≥18 years who underwent non-cardiac and non-neurosurgical surgeries and experienced perioperative ischemic stroke in the First Affiliated Hospital of Henan University of Science and Technology from January 2015 to January 2022,forming the stroke group.A control group of 160 patients without perioperative ischemic stroke was selected in a 1:4 case-control ratio,matched for gender,age,date of operation,and the surgeon.Clinical data and preoperative risk assessment of cerebrovascular events(including the single or combined application of head CT/MRI,transcranial Doppler ultrasound,carotid ultrasound,and neurological consultation)of the two groups of patients were collected and statistically analyzed.Multiple logistic regression analysis was used to identify risk factors associated with perioperative ischemic stroke.Results The incidence of perioperative ischemic stroke was 0.042%.Multiple logistic analysis results showed that hypertension(OR=7.858,95%CI 2.175-28.388,P=0.002),hyperlipidemia(OR=4.457,95%CI 1.320-15.049,P=0.016),renal insufficiency(OR=8.277,95%CI 1.480-46.282,P=0.016),and intraoperative hypotension(OR=3.862,95%CI 1.211-12.317,P=0.022)were independent risk factors for perioperative ischemic stroke in non-cardiac and non-neurological surgeries;preoperative cerebrovascular risk assessment(OR=0.130,95%CI 0.031-0.542,P=0.005)was a protective factor against it.Conclusions The incidence of perioperative ischemic stroke in non-cardiac and non-neurosurgical surgery is low but has a poor prognosis.Hypertension,hyperlipidemia,renal insufficiency,and postoperative hypotension are risk factors for perioperative ischemic stroke,while preoperative cerebrovascular event risk assessment is beneficial to reducing its incidence.

Aim To investigate the synergistic sensiti-zation effect of saikosaponin D(SSD)combined with temozolomide(TMZ)on glioblastoma cells(GBM)and its molecular mechanism.Methods The sensitiv-ity of RG-2,U251 and LN-428 GBM cell lines to SSD and TMZ was analyzed by CCK-8 method combined with HE staining,and the optimal compatible concen-tration was screened.The effect of HE staining com-bined with Hoechst fluorescence staining on the prolif-eration of GBM cell line was detected by clonal forma-tion experiment.The autophagosome formation of GBM cells was observed by monodansylcadaverine(MDC)staining.The expression and distribution of endoplas-mic reticulum stress-related factors and apoptosis and autophagy proteins were detected by Western blot and ICC.Results The sensitivity order of GBM cells to TMZ was RG-2＞U251＞LN-428.The results of com-bined administration showed the synergistic inhibitory effect of SSD combined with TMZ on proliferation of GBM cell lines,which was confirmed by cell cloning formation experiment.Compared with the TMZ group,Hoechst fluorescence staining showed a significant in-crease in the number of nuclear bright staining in the combined administration group.MDC fluorescence staining showed that there were more dense green parti-cles in the cytoplasm of SSD/TMZ plus group than that of TMZ group.Western blot results showed that com-pared with TMZ group,the expression of ER stress markers GRP78,CHOP,p-PERK and ATF6 signifi-cantly increased in SSD/TMZ group(P＜0.05).The expressions of apoptosis proteins caspase-12,caspase-9,caspase-3,cleaved caspase-3,Bax and autophagy proteins LC3 and Beclin-1 significantly increased(P＜0.05),which were verified by ICC test.Conclusions SSD can cooperate with TMZ to inhibit the prolifera-tion of GBM cells and induce apoptosis and autophagy,and enhance the sensitivity of GBM cells to TMZ by ac-tivating endoplasmic reticulum stress pathway.

Objective:To evaluate oncological and reproductive outcomes of women ≤40 years undergoing fertility-sparing surgery (FSS) for stage Ⅱ or Ⅲ borderline ovarian tumor (BOT).Methods:The patients with BOT and ≤40 years old with stage Ⅱ-Ⅲ BOT who underwent FSS enrolled from the First Affiliated Hospital of Zhengzhou University between January 2011 and March 2023 were analyzed retrospectively. The clinical data and follow-up results were obtained and analyzed. The univariate and multivariate Cox proportional hazard regression analysis were used to explore high-risk factors associated with prognosis. Additionally, pregnancy outcomes were also analyzed.Results:(1) A total of 79 patients with stage Ⅱ-Ⅲ BOT who have been treated with FSS were conducted, with an average age of (27.5±6.7) years old. The median tumor maximum diameter were 10.4 cm (range: 4.8-90.0 cm). The International Federation of Gynecology and Obstetrics (FIGO) stage was stage Ⅱ in 45 cases and stage Ⅲ in 34 cases. According to the pathological types, there were 48 cases of serous tumor, 21 cases of mucinous tumor, 1 case of endometrioid tumor, and 9 cases of mixed types. There were 41 cases of unilateral ovarian involvement, 38 cases of bilateral ovarian involvement. There were 5 cases of microinvasion, 17 cases of micropapillary subtype. Extra-ovarian invasive implants were found in 5 cases, and there were 31 cases of merged ascites. (2) Tumor outcomes: the median follow-up time from primary cytoreduction were 58 months (range: 8-146 months). At the end of the observation period, 24 cases (30%, 24/79) recurred, among them 5 cases had two recurrences and 2 cases had three recurrences. There were 2 cases (3%, 2/79) of death and 1 case (1%, 1/79) of survival with tumor. (3) Analysis of prognostic risk factors: the results of univariate analysis showed that mucinous tumor, tumor maximum diameter >13.15 cm, FIGO stage Ⅲ, merged ascites, micropapillary subtype, invasive implantation, and bilateral ovarian involvement were independent risk factors (all P<0.05) for disease-free survival (DFS). FIGO stage Ⅲ ( HR=4.555, 95% CI: 1.525-13.607; P=0.007) and micropapillary subtype ( HR=2.396, 95% CI: 1.003-5.725; P=0.049) were found to be related to DFS through the multivariable Cox proportional hazard regression analysis. (4) Pregnancy outcomes: among the patients with fertility intentions 36 cases (46%,36/79), 29 cases (81%, 29/36) had successful pregnancies, and 27 cases (75%, 27/36) had successful births. Conclusions:Patients with stage Ⅱ-Ⅲ BOT underwent FSS have favorable survival and pregnancy rates. Micropapillary subtypes and FIGO staging (stage Ⅲ) are the significant risk factors of DFS.

OBJECTIVE: Ginsenoside Rh1 (G-Rh1) has been confirmed to inhibit the growth of breast cancer and colon cancer, but its therapeutic effect on hepatocellular carcinoma (HCC) is unclear. This study investigates the therapeutic effect of G-Rh1 on HCC as well as the underlying mechanism. METHODS: Bioinformatics methods were used to analyze glucocorticoid receptor (GR) expression and the tumor microenvironment in HCC tissues from HCC patients. The effect of G-Rh1 on HCC cells was investigated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The therapeutic effect of G-Rh1 was investigated in vivo using subcutaneous transplantation models in C57BL/6J and nude mice. Additionally, the proportion of infiltrating immune cells in tumors was analyzed using flow cytometry, the GR and major histocompatibility complex class-I (MHC-I) expression of HCC cells after G-Rh1 treatment was analyzed using Western blotting, and G-Rh1-treated Hepa1-6 cells were cocultured with bone marrow-derived dendritic cells and B3Z T cells to further analyze the ability of G-Rh1 to induce dendritic cell (DC) maturation and CD8⁺ T cell activation. RESULTS: GR expression was upregulated in HCC tissues, and high GR expression was associated with a worsened immune microenvironment. In vitro studies showed that G-Rh1 had no significant effect on the proliferation of HCC cells, while in vivo studies showed that G-Rh1 exerted antitumor effects in C57BL/6J mice but not in nude mice. Further research revealed that G-Rh1 ameliorated the immunosuppressive tumor microenvironment, thereby enhancing the antitumor effects of lenvatinib by increasing the infiltration of CD8⁺ T cells, mature DCs, and MHC-I-positive cells. MHC-I was upregulated by G-Rh1 via GR suppression. Moreover, overexpression of GR abolished the G-Rh1-mediated promotion of MHC-I expression in Huh7 cells, as well as the maturation of DCs and the activation of CD8⁺ T cells. CONCLUSION G-Rh1 can regulate the immune microenvironment of HCC by targeting GR, thus increasing the antitumor effect of lenvatinib. Please cite this article as: Wang XH, Fu YL, Xu YN, Zhang PC, Zheng TX, Ling CQ, Feng YL. Ginsenoside Rh1 regulates the immune microenvironment of hepatocellular carcinoma via the glucocorticoid receptor. J Integr Med. 2024; 22(6): 710-720.
Carcinoma, Hepatocellular/genetics* ; Ginsenosides/pharmacology* ; Animals ; Liver Neoplasms/genetics* ; Receptors, Glucocorticoid/genetics* ; Tumor Microenvironment/drug effects* ; Humans ; Mice, Inbred C57BL ; Mice ; Mice, Nude ; Cell Line, Tumor ; Male ; Dendritic Cells/drug effects*

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

Abstract: Objective To analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) in Ankang City from 2011 to 2021, so as to provide a scientific basis for the formulation of PTB prevention and control strategy. Methods Descriptive statistics were used to analyze the epidemiological characteristics of PTB in Ankang City from 2011 to 2021, and a time series model was established to quantitatively predict the incidence of pulmonary tuberculosis in 2023. Results The incidence rate in Ankang City showed a significant upward trend from 2011 to 2017, and a more obvious downward trend in 2017-2021 (P<0.05), and the decrease rate in 2021 was 40.36% compared with that in 2017. The proportion of etiological positivity increased from 12.5% in 2014 to over 50.00% after 2019. The incidence season was mainly concentrated in the first quarter, accounting for 28.39% of the annual incidence. High incidence areas were concentrated in the south of Ankang: Langao County, Ziyang County and Zhenping County, with 128.32/100 000, 117.07/100 000 and 110.44/100 000, respectively. Low incidence areas were located in the north of Ankang: Ningshan County, with 60.62/100 000. Farmers and students were the high incidence groups, accounting for 81.80% and 4.97% of the total cases respectively. The incidence of young children was relatively low, but cases were reported every year. The incidence rate of male was 2.39 times that of female. The age of onset increased significantly from 15 years old, and the peak incidence was in the age group of 60-<80 years old, followed by the age group of 45-<60 years old, the average annual incidence was 136.44/100 000 and 104.47/100 000, respectively. The model ARIMA(0,1,1)(0,1,1)12 predicted that the incidence of the disease generally increased from October 2022 to March 2023, then steadily decreased, and increased again in December. Conclusions The incidence of tuberculosis varies in different areas of Ankang City, and males, farmers, students and the elderly are all factors of high incidence of tuberculosis. Therefore, different prevention and control strategies should be adopted according to the characteristics of population in different areas. The number of cases in Ankang City in 2023 showed an overall downward trend, which can provide a reference for the prevention and control of PTB.