OBJECTIVE To investigate the effects of galangin on rheumatoid arthritis （RA） in rats by regulating the Janus kinase 3 （JAK3）/signal transducer and activator of transcription 3 （STAT3） pathway. METHODS Fifty male SD rats were taken， and an emulsion composed of bovine type Ⅱ collagen and Freund’s complete adjuvant was injected subcutaneously to establish an induced arthritis model. The rats that were successfully modeled were randomly divided into model group， low， medium and high dose groups of galangin （1， 5， 15 mg/kg）， and methotrexate group （positive control， 2 mg/kg）， with 10 rats in each group. Another 10 normal rats were taken as the normal group. Starting from the 15th day of modeling， each group of rats was gavaged with the corresponding drug solution or normal saline containing 0.5% Tween 80 once a day for 28 consecutive days. The arthritis index （AI） scores and paw volume of rats were compared before and after gavage administration. Twenty-four hours after the last administration， the serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， IL-4 and IL-10 were determined， the pathological changes in ankle joint synovial tissue were observed， and the protein expressions of UNC-51 like kinase 1 （ULK1）， Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， B cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， caspase-3， JAK3， phosphorylated JAK3 （p-JAK3）， STAT3 and phosphorylated STAT3 （p-STAT3） in the synovial tissue of the ankle joint were detected， as well as the fluorescence intensity of LC3-positive areas. RESULTS Compared with the model group， the pathological changes such as cellular proliferation of ankle joint synovial tissue and infiltration of inflammatory cells in rats of each administration group showed improvement. Moreover， their AI scores and paw pad volumes （on day 28 after gavage）， the levels of IL-6 and TNF-α， the protein expression of Bcl-2， and the phosphorylation levels of JAK3 and STAT3 were all significantly reduced （ P ＜0.05）. The levels of IL-4 and IL-10， the protein expressions of ULK1， Beclin-1， Bax， caspase-3 and LC3， as well as the fluorescence intensity of LC3-positive areas， were all significantly increased （ P ＜0.05）. Moreover， the effect of galangin was in a dose-dependent manner （ P ＜0.05）. CONCLUSIONS Galangin can induce sustained autophagy in synovial tissue cells of RA rats， promote cell apoptosis， inhibit synovial cell proliferation， and alleviate persistent inflammatory responses. The above anti-RA effects may be related to the inhibition of the JAK3/STAT3 pathway.

Objective: : The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs). Methods: : A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway. Results: : The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased. Conclusion : High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

Objective: : The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs). Methods: : A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway. Results: : The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased. Conclusion : High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

Objective: : The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs). Methods: : A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway. Results: : The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased. Conclusion : High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

Objective: : The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs). Methods: : A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway. Results: : The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased. Conclusion : High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

OBJECTIVE To discuss the impact of Wenyang lishui formula on ventricular remodeling in rats with pulmonary hypertension-induced right heart failure （RHF） based on the Hippo/Yes-associated protein （YAP） signaling pathway. METHODS Ten rats were randomly selected as the control group. The remaining 63 rats were given a single intraperitoneal injection of monocrotaline to establish the pulmonary hypertension-induced RHF model. The 50 rats that successfully underwent the model establishment were randomly divided into the RHF group， low-dose group of Wenyang lishui formula （4.25 g/kg）， high-dose group of the Wenyang lishui formula （17.00 g/kg）， furosemide group （20 mg/kg）， and high-dose group of Wenyang lishui formula+ Hippo/YAP signaling pathway activator group （17.00 g/kg of Δ Wenyang lishui formula+16 mg/kg of PY-60）， with 10 rats in each group. The rats in each group were given the corresponding drug solution or normal saline by gavage or/andtail vein injection， once a day， for 4 consecutive weeks. During the experiment， the general conditions of the rats in each group were observed； after the last administration， the right ventricular diameter， right atrial diameter， end-diastolic volume， pulmonary artery blood flow acceleration time （PAAT） and its ratio to ejection time （ET） （PAAT/ET）， pulmonary artery pressure and its ratio to pulmonary arterial flow velocity （pulmonary artery pressure/velocity） were measured. The plasma levels of brain natriuretic peptide and angiotensin Ⅱ （Ang Ⅱ） were detected. The pathological changes of the right ventricular tissue were observed， and the collagen volume fraction， the phosphorylation levels of the large tumor suppressor 1/2 （LATS1/2） and YAP， and the protein expression of the transcriptional coactivator of PDZ-binding motif （TAZ） were also detected. RESULTS Compared with the RHF group， the rats in Wenyang lishui formula low-dose and high-dose groups showed improved hair color， movement， diet， and mental state. The atrophy of right ventricular myocardial cells， the increase of inflammatory cells， collagen deposition， and hypertrophy of myocardial fibers were significantly alleviated. The right ventricular internal diameter， right atrial internal diameter， end-diastolic volume， pulmonary artery pressure， pulmonary artery pressure/velocity， the plasma levels of brain natriuretic peptide and AngⅡ ， collagen volume fraction， the phosphorylation level of YAP and protein expression of TAZ were significantly decreased， while the PAAT， PAAT/ET and the phosphorylation level of LATS1/2 were significantly increased （P＜0.05）. PY-60 could significantly reverse the improvement effects of high-dose Wenyang lishui formula on the above quantitative indicators （P＜ 0.05）. CONCLUSIONS Wenyang lishui formula can restore the right heart function of pulmonary hypertension-induced RHF rats， reduce their pulmonary artery pressure， alleviate the pathological changes in their cardiac tissues， and the above effects may be related to the activation of Hippo expression and the inhibition of YAP phosphorylation.

OBJECTIVE To investigate the effects of aucubin （AU） on the proliferation and tumor growth of prostate cancer （PC） cells by regulating the protein kinase B （Akt）/murine double minute2 （MDM2）/p53 signaling pathway. METHODS Prostate cancer cell PC3 were separated into control group， 50 μmol/L AU group， 100 μmol/L AU group， SC79 （Akt activator） group （5 μmol/L）， and 100 μmol/L AU+SC79 group. The cell cloning and proliferation ability were investigated； the rate of cell apoptosis and the expressions of Akt/MDM2/p53 signaling pathway-related protein were detected. Meanwhile， xenograft tumor models of nude mice were constructed and separated into tumor group， AU group （80 mg/kg）， SC79 group （50 mg/kg）， and AU+SC79 group （80 mg/kg AU+50 mg/kg SC79）， with 10 mice in each group. They were given relevant medicine， once a day， for 21 d. After the last medication， tumor weight was determined， and the expressions of nucleus-associated antigen （Ki-67） and Akt/MDM2/p53 signaling pathway-related protein were detected in tumor tissue. RESULTS In the cell experiment， compared with control group， the cell clonal formation number， proliferation rate and phosphorylation levels of Akt and MDM2 protein in 50 μmol/L AU and 100 μmol/L AU groups were significantly decreased （P＜0.05）， while the cell apoptosis rate and p53 protein expression levels were significantly increased （P＜0.05）； however， the change trend of each index in SC79 group was opposite （P＜0.05）. Compared with 100 μmol/L AU group， the cell clonal formation number， proliferation rate and phosphorylation levels of Akt and MDM2 protein in 100 μmol/L AU+SC79 group were significantly increased （P＜0.05）， while cell apoptosis rate and p53 protein expression levels were significantly decreased （P＜0.05）； however， compared with SC79 group， the changing trend of indexes was the opposite （P＜0.05）. In the in vivo experiment， compared with the tumor group， the tumor mass and Ki-67 positive expression and the phosphorylation levels of Akt and MDM2 protein in nude mice of AU group were significantly decreased （P＜0.05）， and the expression level of p53 protein was significantly increased （P＜0.05）， but the changing trend of above indexes of nude mice in SC79 group were opposite （P＜0.05）. Compared with AU group， the tumor mass， Ki-67 positive expression and phosphorylation levels of Akt and MDM2 protein in tumor tissues of nude mice in AU+SC79 group were significantly increased （P＜0.05）， while the expression level of p53 protein was significantly decreased （P＜0.05）； however， compared with SC79 group， the changing trend of above indexes was opposite （P＜0.05）. CONCLUSIONS AU can inhibit PC cell proliferation and tumor growth by inhibiting Akt/MDM2/p53 signaling pathway.

Objective : To analyze the length of hospital stay of patients with heart failure in a multicenter cohort in order to explore the influencing factors of length of stay and provide data support for further intervention. Methods: A total of 2 794 patients enrolled in the multicenter prospective heart failure cohort were divided into two groups: long hospital stay group (≥9 days) and short hospital stay group ( < 9 days) . The general data of the two groups were compared, and the factors with statistical difference in univariate analysis were included in Logistic multifactor regression analysis to explore the difference in length of hospital stay between the two groups. According to left ventricular ejection fraction(LVEF), patients were divided into heart failure with preserved reduced ejection fraction (HFpEF)group, heart failure with mildly reduced ejection fraction(HFmrEF)group and heart failure with reduced ejection fraction(HFrEF) group, and Logistic multifactor regression analysis was performed to find influencing factors. Results : Logistic multifactor regression analysis showed that LVEF, pneumonia, N⁃terminal pro⁃B⁃type natriuretic peptide(NT⁃proBNP), serum sodium, cardiac resynchronization therapy( CRT) or implantable cardioverter defibrillator(ICD)implantation, β blockers, aldosterone receptor antagonists, positive inotropic drugs and vasodilators were all factors influencing the hospitalization of HF patients. In the HFpEF, HFmrEF, and HFrEF groupsCRT/ICD implantation, positive inotonic drugs, and vasodilator use were suggested to be common factors affecting length of hospital stay in all three groups. Conclusion LVEF, pneumonia, NT⁃proBNP, serum sodium, CRT or ICD implantation, β blockers, aldosterone receptor antagonists, positive inotropic drugs and vasodilators are the influencing factors of hospitalization time in HF patients.

Objective:To analyze the epidemic characteristics of Cornona virus disease 2019 (COVID-19) in Wangkui County, Heilongjiang Province, and to provide a reference for optimizing epidemic prevention and control strategies.Methods:The epidemic characteristics of COVID-19 in Wangkui County, Heilongjiang Province in January 2021 were analyzed by applying the national infectious disease report system and information management system of Heilongjiang Provincial Center for Disease Control and Prevention, the public health emergency report management information system, the epidemiological investigation report of the Heilongjiang Provincial Center for Disease Control and Prevention and Suihua Municipal Certer for Disease Control and Prevention, and the epidemic information publicly released by the Health Commission of Heilongjiang Province.Results:From January 9 to February 5, 2021, 804 cases infected with Cornona virus were reported in Wangkui County, with an infection rate of 280.29/100 000. The epidemic affected 20 districts and counties in 6 cities, including Suihua, Harbin, Mudanjiang, Qiqihar, Yichun and Daqing. The sex ratio of male to female was 1.08 ∶ 1.00 (418 ∶ 386), the age ranged from 3 months to 93 years old, and the median age was 50 years old. The proportion of confirmed cases and asymptomatic infection was 1.23 ∶ 1.00 (444 ∶ 360), there were significant differences in gender, age and occupation between them ( P < 0.05). There were 314 places where the aggregation epidemic occurred, with family aggregation as the main way (300 households, 95.54%). The places with the highert average number of cases were banquets (25.75 cases/place) and grocery stores/chess and card rooms (16.00 cases/place). Conclusions:In January 2021, the epidemic of COVID-19 in Wangkui County is a typical outbreak in rural areas of North China. The main reasons for the rapid spread of the epidemic are a large number of gathering activities, frequent contact of personnel in confined spaces and other factors.

OBJECTIVE: To construct a polylactic acid-glycolic acid-polyethylene glycol (PLGA-PEG) nanocarrier (N-Pac-CD133) coupled with a CD133 nucleic acid aptamer carrying paclitaxel for eliminating lung cancer stem cells (CSCs). METHODS: Paclitaxel-loaded N-Pac-CD133 was prepared using the emulsion/solvent evaporation method and characterized. CD133⁺ lung CSCs were separated by magnetic bead separation and identified for their biological behaviors and gene expression profile. The efficiency of paclitaxel-loaded N-Pac-CD133 for targeted killing of lung cancer cells was assessed in vitro. SCID mice were inoculated with A549 cells and received injections of normal saline, empty nanocarrier linked with CD133 aptamer (N-CD133), paclitaxel, paclitaxel-loaded nanocarrier (N-Pac) or paclitaxel-loaded N-Pac-CD133 (n=8, 5 mg/kg paclitaxel) on days 10, 15 and 20, and the tumor weight and body weight of the mice were measured on day 40. RESULTS: Paclitaxel-loaded N-Pac-CD133 showed a particle size of about 100 nm with a high encapsulation efficiency (>80%) and drug loading rate (>8%), and was capable of sustained drug release within 48 h. The CD133⁺ cell population in lung cancer cells showed the characteristic features of lung CSCs, including faster growth rate (30 days, P=0.001) and high expressions of tumor stem cell markers OV6(P < 0.001), CD133 (P=0.001), OCT3/4 (P=0.002), EpCAM (P=0.04), NANOG (P=0.005) and CD44 (P=0.02). Compared with N-Pac and free paclitaxel, paclitaxel-loaded N-Pac-CD133 showed significantly enhanced targeting ability and cytotoxicity against lung CSCs in vitro (P < 0.001) and significantly reduced the formation of tumor spheres (P < 0.001). In the tumor-bearing mice, paclitaxel-loaded N-Pac-CD133 showed the strongest effects in reducing the tumor mass among all the treatments (P < 0.001). CONCLUSION CD133 aptamer can promote targeted delivery of paclitaxel to allow targeted killing of CD133⁺ lung CSCs. N-Pac-CD133 loaded with paclitaxel may provide an effective treatment for lung cancer by targeting the lung cancer stem cells.
Animals ; Cell Line, Tumor ; Drug Carriers ; Lung ; Mice ; Mice, SCID ; Nanoparticles ; Neoplasms ; Neoplastic Stem Cells ; Paclitaxel/pharmacology* ; Polyethylene Glycols/pharmacology*