ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

Objective: To investigate the effect of activation of the stimulator of interferon genes(STING) pathway on macrophage polarization function and its role in T-cell response. Methods: Mouse macrophage RAW264.7 cells were used.STING signaling related proteins in RAW264.7 macrophage treated with STING agonist diABZI were analyzed by Western blot,including TANK-binding kinase-1(TBK1),interferon regulatory factor-3(IRF3),STING,p-TBK1,p-IRF3,p-STING.The polarization of macrophage RAW264.7 cells treated with diABZI was analyzed by flow cytometry.Co-culture of diABZI-treated RAW264.7 macrophage and T cells was applied to evaluate the change of T cell response. Results: STING signaling related proteins were upregulated in macrophage RAW264.7 cells treated with diABZI for 3 hours.The expression of CD86 was upregulated on the surface of macrophages after 12 hours of diABZI treatment,and the CD86/CD206 ratio was elevated,which presented the M1 polarization phenotype.When coculturing diABZI-treated macrophage RAW264.7 cells with T cells,the cytokine secretion ability of T cells including CD4+T and CD8+T cells was enhanced and the expression of CD107a in CD8+T cells was upregulated. Conclusion STING signaling induces M1 polarization of macrophages which enhance the function of T cells,especially CD8+T cell immune response.

Objective:To establish an in vivo infection model of West Nile virus (WNV) pseudovirus and evaluate the neutralizing activity of antibody WNV-XH1.Methods:A stable cell line that can package the WNV pseudovirus was established in the early stage to prepare the pseudovirus supernatant. The supernatant was concentrated and infected BHK21 cells to detect the titer of the pseudovirus. After intraperitoneal injection of the pseudovirus into C57BL/J mice, bioluminescence imaging was performed to observe the infection status of the pseudovirus in the mice. After simultaneous infection, blood was collected and ELISA was used to detect NS1 levels in mouse serum. The in vivo functional activity of antibody WNV-XH1 was evaluated using the established mouse infection model.Results:Fluorescence was detected in C57BL/J mice infected with WNV pseudovirus, and the NS1 levels in the peripheral blood serum of mice infected with pseudovirus were significantly higher than those of non infected mice (1.453±0.09vs0.305±0.018). After intravenous administration of WNV-XH1 antibody before the attack, the fluorescence signal in the mice decreased and the serum NS1 level decreased (0.384±0.015).Conclusions:A successful in vivo infection model of WNV pseudovirus was established, and it was confirmed that the antibody WNV-XH1 had a protective effect against WNV pseudovirus infection in vivo.

Objective:To explore the latent profile and characteristics of social isolation in patients with hematologic malignancy, and to analyze its related influencing factors, and to provide reference for improving social phobia disorder in different patients and implementing targeted intervention.Methods:This study was a cross-sectional survey. A convenient sampling method was used to select hematologic malignancy patients who were treated in Qilu Hospital of Shandong University from January 2022 to January 2023. General information questionnaire, the General Alienation Scale (GAS), and the Social Support Rating Scale(SSRS) were used for investigation. Latent profile was analyzed using the categories of social isolation in patients with hematologic malignancy, and univariate and multinomial logistic regression analysis were used to analyze relevant influencing factors.Results:A total of 195 survey subjects were included, of which 108 males and 87 females, aged (49.78 ± 13.52) years. The scores of GAS and SSRS were (43.21 ± 6.09) and (42.52 ± 6.77) respectively. The social isolation in patients with hematologic malignancy could be divided into 3 latent profiles, namely low-risk isolation 15.4% (30/195), medium-risk isolation 68.2%(133/195), and high-risk isolation16.4% (32/195). Multinomial Logistic regression analysis showed that age ( OR=0.941, 95% CI 0.894-0.990), percapita monthly income of families ( OR=0.050, 95% CI 0.004-0.657), primary caregivers (parents) ( OR=0.025, 95% CI 0.003-0.227), place of residence (town)( OR=0.170, 95% CI 0.039-0.749), disease type (leukemia) ( OR=15.610, 95% CI 2.973-81.979), disease type(lymphoma) ( OR=10.986, 95% CI 2.032-59.413) were the influencing factors of medium-risk isolation (all P<0.05). Age ( OR=0.933, 95% CI 0.880-0.988), percapita monthly income of families ( OR=0.029, 95% CI 0.002-0.525), primary caregivers (parents) ( OR=0.076, 95% CI 0.006-0.900), disease type (leukemia)( OR=19.257, 95% CI 2.580-143.723), disease type (lymphoma)( OR=9.952, 95% CI 1.290-76.763), social support ( OR=0.877, 95% CI 0.786-0.980) were the influencing factors of high-risk isolation (all P<0.05). Conclusions:The social isolation among patients with hematologic malignancy had apparent classification characteristics. It could be divided into three potential profiles. It is suggested that medical staff should take targeted social and psychological support based on different types of patients, improve their psychological and social outcomes, and utilize existing resources to implement intervention measures to help them adapt and return to society.

Since emergence,the influenza virus has triggered numerous global pandemics and claimed more than ten million lives.This virus poses not only a severe threat to human life and health,but significant challenges to global economy and public health.The research on highly pathogenic influenza virus strains(such as H5 and H7)necessitates the use of biosafety level 3 laboratories,which significantly escalates the experimental risks and costs.The pseudovirus technology,as a relatively safe and effective research technique,has been applied in the studies of various high-risk viruses.Thanks to constant research and refinement,the pseudovirus technology for the influenza virus currently boasts such advantages as user-friendliness and good safety,and has been extensively used antibody neutralization and screening of antiviral drugs.This article reviews the research progress in the pseudovirus technology for the influenza virus.

Objective:To investigate the effect and regulation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on islets function and NOD-like receptor family, pyrin domain containing 3 (NLRP3) and autophagy in type 2 diabetic mellitus (T2DM) mice.Methods:Experimental study. Twenty, 8-week-old, male C57BL/6J mice were selected and divided into a normal control group ( n=5) and a high-fat feeding modeling group ( n=15). The model of T2DM was established by high-fat feeding combined with intraperitoneal injection of low-dose streptozotocin. After successful modeling, those mice were divided into a diabetes group ( n=7) and a UC-MSCs treatment group ( n=7). The UC-MSCs treatment group was given UC-MSCs (1×10 6/0.2 ml phosphate buffer solution) by tail vein infusion once a week for a total of 4 weeks; the diabetes group was injected with the same amount of normal saline, and the normal control group was not treated. One week after the treatment, mice underwent intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and then the mice were sacrificed to obtain pancreatic tissue to detect the expressions of interleukin-1β (IL-1β) and pancreatic and duodenal homeobox 1 (PDX-1) by immunofluorescence. The bone marrow-derived macrophages were stimulated with lipopolysaccharide and adenosine triphosphate (experimental group) in vitro, then co-cultured with UC-MSCs for 24 h (treatment group). After the culture, enzyme-linked immunosorbent assay was used to detect the secretion level of IL-1β in the supernatant, and immunofluorescence staining was used to detect the expression of NLRP3 inflammasome, and related autophagy proteins. Statistical analysis was performed using unpaired one-way analysis of variance, repeated measure analysis of variance. Results:In vivo experiments showed that compared with the diabetes group, the UC-MSCs treatment group partially repaired islet structure, improved glucose tolerance and insulin sensitivity (all P<0.05), and the expression of PDX-1 increased and IL-1β decreased in islets under confocal microscopy. In vitro experiments showed that compared with the experimental group, the level of IL-1β secreted by macrophages in the treatment group was decreased [(85.9±74.6) pg/ml vs. (883.4±446.2) pg/ml, P=0.001], the expression of NLRP3 inflammasome and autophagy-related protein P62 was decreased, and the expressions of microtubule-associated protein 1 light chain 3β (LC3) and autophagy effector Beclin-1 were increased under confocal microscopy. Conclusions:UC-MSCs can reduce the level of pancreatic inflammation in T2DM mice, preserving pancreatic function. This might be associated with the ability of UC-MSCs to inhibit the activity of NLRP3 inflammasomes in macrophages and enhance autophagy levels.

Objective:To analyze the effects of chronic obstructive pulmonary disease (COPD) combined with obstructive sleep apnea hypopnea syndrome (OSAHS) on hypercapnia and its related factors.Methods:In this cross-sectional study, patients with stable COPD were continuously recruited from July 2016 to December 2018 in the Respiratory Department of Peking University Third Hospital. General clinical data of patients were collected, and lung function test, arterial blood gas analysis and portable sleep monitoring were also conducted. Patients with COPD complicated with apnea hypopnea index (AHI)≥10 times/h and apnea events being mainly blockage-type events, accompanied by snoring, sleep apnea, daytime sleepiness and other symptoms were defined as overlapping group, patients with COPD complicated with AHI<10 times/h were defined as simple COPD group. Correlation analysis and logistic regression model were used to explore the determinants of daytime hypercapnia in patients with COPD.Results:Compared with simple COPD group, the median arterial partial pressure of carbon dioxide (PaCO 2) was significantly higher in the overlapping group (42.00 vs 38.95 mmHg (1 mmHg=0.133 kPa), P<0.001), and the rate of daytime hypercapnia was significantly higher (23.3% vs 3.3%, P=0.002). PaCO 2 was correlated with forced vital capacity (FVC), percent predicted forced expiratory volume in one second (FEV 1%pred), the ratio of residual volume (RV) to total lung capacity (TLC), AHI, nocturnal average transcutaneous oxygen saturation (SpO 2), nocturnal minimum SpO 2 and the total sleep time spent with SpO 2≤90% (T90) (all P<0.05). In logistic regression analysis, after adjusting for age, sex, and body mass index (BMI), only severe OSAHS, GOLD Ⅲ-Ⅳ grade (FEV 1%pred<50%), and T90>1% were independent risk factors for hypercapnia. Conclusions:OSAHS can increase the risk of hypercapnia in patients with COPD. AHI, lung function injury and T90 are closely related to hypercapnia.

Objective:To evaluate the effect of dexmedetomidine on the expression of DNA methyltransferases in septic mice with acute lung injury.Methods:Forty-eight clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (group Sham), sham operation + dexmedetomidine group(group Sham+ DEX), sepsis group (group Sepsis) and sepsis + dexmedetomidine group(group Sepsis+ DEX). Sepsis model was established by cecal ligation and puncture(CLP)in anesthetized mice. At 30 min before model preparation, dexmedetomidine 0.05 μg/g (in 0.5 ml of normal saline) was administered in Sham + DEX and Sepsis + DEX groups, and normal saline 0.5 ml was given instead in Sham and Sepsis groups. The mice were sacrificed at 24 h after CLP, and the lung tissue was taken to determine the wet to dry lung weight ratio, contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and high mobility group box-1 (HMGB-1), activities of superoxide dismutase (SOD) and myeloperoxidase (MPO), and content of malondialdehyde (MDA) (by enzyme-linked immunosorbent assay), global DNA methylation (by colorimetric assay), and expression of DNA methyltransferases (DNMTl, DNMT3a, DNMT3b) (by Western blot) and to examine the histopathological changes of lung tissues (by HE staining) which were scored. Results:Compared with group Sham, the lung injury score, wet/dry lung weight ratio, contents of IL-6, TNF-α and HMGB1 and MDA, MPO activity and global DNA methylation were significantly increased, SOD activity was decreased, and the expression of DNMT1 and DNMT3a was up-regulated in group Sepsis and group Sepsis+ DEX ( P<0.05), and no significant change was found in the aforementioned indexes in group Sham+ DEX ( P>0.05). Compared with group Sepsis, the lung injury score, wet/dry lung weight ratio, contents of IL-6, TNF-α and HMGB1 and MDA, MPO activity and global DNA methylation were significantly decreased, SOD activity was increased, and the expression of DNMT1 and DNMT3a was down-regulated in group Sepsis+ DEX ( P<0.05). Conclusions:The mechanism by which dexmedetomidine reduces acute lung injury is related to inhibition of up-regulation of DNMT1 and DNMT3a expression in septic mice.

Humans ; Air Pollutants ; Sleep Apnea, Obstructive ; Polysomnography ; Sleep ; Pulmonary Disease, Chronic Obstructive

Objective:To construct a chronic obstructive pulmonary disease (COPD) assessment test (CAT) score prediction model based on a deep network fused with air data, and to explore its significance.Methods:From February 2015 to December 2017, the outdoor environmental monitoring air data near the residential area of the patients with COPD from the Respiratory Outpatient Clinics of Peking University Third Hospital, Peking University People′s Hospital and Beijing Jishuitan Hospital were collected and the daily air pollution exposure of patients was calculated. The daily CAT scores were recorded continuously. The CAT score of the patients in the next week was predicted by fusing the time series algorithm and neural network to establish a model, and the prediction accuracy of the model was compared with that of the long short-term memory model (LSTM), the LSTM-attention model and the autoregressive integrated moving average model (ARIMA).Results:A total of 47 patients with COPD were enrolled and followed up for an average of 381.60 days. The LSTM-convolutional neural networks (CNN)-autoregression (AR) model was constructed by using the collected air data and CAT score, and the root mean square error of the model was 0.85, and the mean absolute error was 0.71. Compared with LSTM, LSTM-attention and ARIMA, the average prediction accuracy was improved by 21.69%.Conclusion:Based on the air data in the environment of COPD patients, the fusion deep network model can predict the CAT score of COPD patients more accurately.