BACKGROUND: Pulmonary arterial hypertension (PAH) presents a significant health burden in Asia and remains a critical challenge. This study aims to delineate the PAH burden in Asia from 1990 to 2021. METHODS: Using the latest data from the Global Burden of Disease 2021, we evaluated and analyzed the distributions and patterns of PAH disease burden among various age groups, sexes, regions, and countries in Asia. Additionally, we examined the associations between PAH disease burden and key health system indicators, including the socio-demographic index (SDI) and the universal health coverage (UHC) index. RESULTS: In 2021, there were 25,989 new PAH cases, 103,382 existing cases, 13,909 PAH-associated deaths, and 385,755 DALYs attributed to PAH in Asia, which accounted for approximately 60% of global PAH cases. The age-standardized rates (ASRs) for prevalence and deaths were 2.05 (95% uncertainty interval [UI]: 1.66-2.52) per 100,000 population and 0.31 (95% UI: 0.23-0.38) per 100,000 population, respectively. From 1990 to 2021, Asia reported the lowest ASRs for PAH prevalence but the highest ASRs for deaths compared to other continents. While the ASRs for prevalence increased slightly, ASRs for mortality and DALYs decreased over time. This increasing burden of PAH was primarily driven by population growth and aging. The burden was especially pronounced among individuals aged ≥60 years and <9 years, who collectively accounted for the majority of deaths and DALYs. Moreover, higher SDI and UHC levels were linked to reduced incidence, but higher prevalence rates. CONCLUSIONS Although progress has been made in reducing PAH-related mortality and DALYs, the disease continues to impose a substantial burden in Asia, particularly among older adults and young children. Region-specific health policies should focus on improving early diagnosis, expanding access to treatment, and effectively addressing the growing PAH burden in the region.
Humans ; Global Burden of Disease ; Male ; Female ; Middle Aged ; Adult ; Asia/epidemiology* ; Prevalence ; Aged ; Pulmonary Arterial Hypertension/mortality* ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Hypertension, Pulmonary/epidemiology*

BACKGROUND: The potential impact of pre-existing coronary artery stenosis (CAS) on right ventricular (RV) function during acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and RV dysfunction in patients with acute PE. METHODS: In this multicenter, case-control study, 89 cases and 176 controls matched for age were enrolled at three study centers (Peking Union Medical College Hospital, Fuwai Hospital, and the Second Affiliated Hospital of Harbin Medical University) from January 2016 to December 2020. The cases were patients with acute PE with CAS, and the controls were patients with acute PE without CAS. Coronary artery assessment was performed using coronary computed tomographic angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression analysis was used to evaluate the association between CAS and RV dysfunction. RESULTS: The percentages of RV dysfunction (19.1% [17/89] vs. 44.6% [78/176], P <0.001) and elevated systolic pulmonary artery pressure (sPAP) (19.3% [17/89] vs. 39.5% [68/176], P = 0.001) were significantly lower in the case group than those in the control group. In the multivariable logistic regression model, CAS was independently and negatively associated with RV dysfunction (adjusted odds ratio [OR]: 0.367; 95% confidence interval [CI]: 0.185-0.728; P = 0.004), and elevated sPAP (OR: 0.490; 95% CI: 0.252-0.980; P = 0.035), respectively. CONCLUSIONS Pre-existing CAS was significantly and negatively associated with RV dysfunction and elevated sPAP in patients with acute PE. This finding provides new insights into RV dysfunction in patients with acute PE with pre-existing CAS.
Humans ; Pulmonary Embolism/complications* ; Case-Control Studies ; Male ; Ventricular Dysfunction, Right/physiopathology* ; Female ; Middle Aged ; Aged ; Coronary Stenosis/complications* ; Logistic Models ; Adult

Objective : To investigate the effects of sinapine on lung tissue inflammation and mucus hypersecretion in asthmatic mice. Methods: Eight-week-old female C57BL/6J mice were randomly divided into Control group, ovalbumin(OVA) group, Sinapine group, and Sinapine+OVA group. The asthmatic mice model were established by intraperitoneal injection of OVA combined with aluminum hydroxide [Al(OH)3] suspension and OVA nasal stimulation. One hour before OVA nasal stimulation, the mice in Sinapine+OVA group and Sinapine group were intraperitoneally injected with sinapine solution, and the mice in OVA group and Control group were treated with the same dose of 0.9% sodium chloride solution. 24 hours after the last OVA stimulation, the inflammation of lung tissue of mice were observed by HE staining; the mucus secretion were evaluated by PAS staining; the mRNA expression levels of Interleukin-4(IL-4), Interleukin-5(IL-5), Interleukin-13(IL-13), tumor necrosis factor-alpha(TNF-α), Mucin 5ac(Muc5ac), and the mRNA of the key genes of Notch pathway such as Notch receptor 1(Notch1), Notch receptor 2(Notch2), Notch receptor 3(Notch3), and hes family bHLH transcription factor 1(Hes1) in lung tissues were detected by real-time fluorescent quantitative PCR(RT-qPCR); the expression levels of Notch1, Notch2, Notch3 and Hes1 proteins were determined by Western blot. Results : Compared with Control group, the inflammation score and PAS score of lung tissues of mice in OVA group increased(P<0.001); the mRNA expression levels of IL-4, IL-5, IL-13, TNF-α, and Muc5ac of mice in OVA group were enhanced(P<0.05); the mRNA and protein expression levels of Notch2, Notch3, and Hes1 of mice in OVA group significantly increased(P<0.001), while there was no significant difference in the mRNA and protein expression levels of Notch1. Compared with OVA group, the inflammation score and PAS score of lung tissues of mice in Sinapine+OVA group decreased(P<0.001); the mRNA expression levels of IL-4, IL-5, IL-13, TNF-α, and Muc5ac of mice in Sinapine+OVA group were reduced(P<0.05); the mRNA and protein expression levels of Notch2, Notch3, and Hes1 of mice in Sinapine+OVA group were downregulated(P<0.05), while there was no significant difference in the mRNA and protein expression levels of Notch1. Conclusion Sinapine can alleviate the lung tissue inflammation and mucus hypersecretion in asthmatic mice, and its mechanism may be related to the inhibition of Notch2/Notch3-Hes1 signal pathway.

OBJECTIVE To investigate the potential therapeutic effect of the sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" from the perspective of immunomodulation and cardioprotection. METHODS Chemical components of the sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" were analyzed by UPLC-Q-TOF-MS and colorimetric methods. Examined tablet’s effects on zebrafish models of macrophage reduction, heart failure, H2O2-induced oxidative stress in myocardial and endothelial cells, and a microglial inflammation model induced by lipopolysaccharide. Immune regulation and cardioprotective effects were evaluated through multiple indicators, including macrophage formation and phagocytosis abilities, anti-neuroinflammation ability, cardiac systolic and diastolic functions, and anti-oxidative stress injury ability in myocardial and endothelial cells. RESULTS The sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" improved macrophage formation and phagocytosis, cardiac systolic and diastolic functions, reduced neuroinflammation, and alleviated oxidative stress in myocardial and endothelial cells, resulting in immunomodulatory and cardioprotective effects. CONCLUSION The sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" maybe a potential therapeutic agent for regulating the immune system and protecting cardiac function.

Gastric cancer(GC)is one of the most common gastrointestinal tumors.As a newly discovered type of non-coding RNAs,transfer RNA(tRNA)-derived small RNAs(tsRNAs)play a dual biological role in cancer.Our previous studies have demonstrated the potential of tRF-23-Q99P9P9NDD as a diagnostic and prognostic biomarker for GC.In this work,we confirmed for the first time that tRF-23-Q99P9P9NDD can promote the proliferation,migration,and invasion of GC cells in vitro.The dual luciferase reporter gene assay confirmed that tRF-23-Q99P9P9NDD could bind to the 3'untranslated region(UTR)site of acyl-coenzyme A dehydrogenase short/branched chain(ACADSB).In addition,ACADSB could rescue the effect of tRF-23-Q99P9P9NDD on GC cells.Next,we used Gene Ontology(GO),the Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA)to find that downregulated ACADSB in GC may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis.Finally,we verified the correlation between ACADSB and 12 ferroptosis genes at the transcriptional level,as well as the changes in reactive oxygen species(ROS)levels by flow cytometry.In summary,this study proposes that tRF-23-Q99P9P9NDD may affect GC lipid metabolism and ferroptosis by targeting ACADSB,thereby promoting GC progression.It provides a theoretical basis for the diagnostic and prognostic monitoring value of GC and opens up new possibilities for treatment.

Objective:To discuss the effect of Aspergillus fumigatus(Af)on DNA damage and interleukin(IL)-33 expression in the human bronchial epithelial cells,and to clarify its related mechanism.Methods:Different concentrations(1,5,and 10 mg·L-1)of Af were used to stimulate the bronchial epithelial BEAS-2B cells to select the appropriate stimulation concentration.When the BEAS-2B cells were treated with N-acetylcysteine(NAC)and Af,the cells were divided into control group,Af group,NAC group,and Af+NAC group.When the BEAS-2B cells were treated with DNA double-strand break repair inhibitor NU7441 and Af,the cells were divided into control group,Af group,NU7441 group,and Af+NU7441 group.The comet assay was used to detect the percentages of comet tail DNA of cells in various groups;immunofluorescence method was used to detect the expression levels of DNA damage-related protein phosphorylated H2AX(yH2AX)in the cells in various groups;2,7-dichlorofluorescein diacetate(DCFH-DA)fluorescence probe was used to detect the levels of reactive oxygen species(ROS)in the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of interleukih-33(IL-33),thymic stromal lymphopoietin(TSLP),and interleukih-25(IL-25)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of phosphorylated nuclear factor κB(p-NF-κB),phosphorylated ataxia telangiectasia mutated(p-ATM),and γH2AX proteins in the cells in various groups.Results:Compared with control group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 1 mg·L-1 Af group showed no significant difference(P＞0.05),while the percentage of comet tail DNA and the expression level of γH2AX in the cells in 5 mg·L-1 Af group were significantly increased(P＜0.01);compared with 5 mg·L-1 Af group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 10 mg·L-1 Af group were significantly increased(P＜0.01).Compared with control group,the ROS levels in the bronchial epithelial cells in 1 mg·L-1 Af group was significantly increased(P＜0.05);compared with 1 mg·L-1 Af group,the ROS level in the cells in 5 mg·L-1 Af group was significantly increased(P＜0.01);compared with 5 mg·L-1 Af group,the ROS level in the cells in 10 mg·L-1 Af group was significantly increased(P＜0.05).After treatment of NAC,compared with Af group,the percentage of comet tail DNA(P＜0.01),the expression level of γH2AX(P＜0.05),and the ROS level(P＜0.01)in the cells in Af+NAC group were significantly decreased;after treatment of NU7441,compared with Af group,the percentage of comet tail DNA and the expression level of yH2AX in the cells in Af+NU7441 group were significantly increased(P＜0.01).The RT-qPCR results showed that after treatment of NAC,compared with control group,the expression level of IL-33 mRNA in the cells in Af group was significantly increased(P＜0.05);compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NAC group was significantly decreased(P＜0.05);after treatment of NU7441,compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NU7441 group was significantly increased(P＜0.05).The Western blotting results showed that after treatment of NAC,compared with control group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af group were significantly increased(P＜0.05);after treatment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NAC group were significantly decreased(P＜0.05);After treat ment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NU7441 group were significantly increased(P＜0.05).Conclusion:Af promotes the IL-33 expression in the human bronchial epithelial cells by causing DNA damage,and its mechanism may be related to the activation of ATM/NF-κB signaling pathway.

Objective:To discuss the effect of Jiegeng Yuanshen Tang(JGYST)on airway tissue inflammation and mucus secretion in the mice with allergic asthma,and to clarify the related mechanism.Methods:Forty male C57BL/J mice were randomly divided into control group,JGYST group,ovalbumin(OVA)group,and OVA + JGYST group.The mice in OVA group and OVA +JGYST group were sensitized with 50 μg OVA via intraperitoneal injection twice weekly,followed by 20 μg OVA nasal drops daily for 7 d to induce asthma;the mice in OVA +JGYST group were gavaged with 200 μL JGYST 1 h before each OVA challenge,and the administration lasted for 7 d;the mice in control group were given equivalent dose of PBS via intraperitoneal injection,nasal drops,and gavage;the mice in JGYST group were given the same dose of PBS for intraperitoneal and nasal administration and gavaged with the same dose of JGYST.The pathomorphology of lung tissue of the mice in various groups was observed by HE staining and periodic acid-Schiff(PAS)staining,and the inflammation and PAS scores were calculated;flow cytometry method was used to detect the numbers of eosinophils,neutrophils,helper T lymphocyte 1(Th1)cells,helper T lymphocyte 2(Th2)cells,and dendritic cells(DCs),as well as the percentage of mature DCs and level of reactive oxygen species(ROS)in lung tissue of the mice in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of interleukin-4(IL-4),interleukin-10(IL-10),and tumor necrosis factor-α(TNF-α)mRNA in lung tissue of the mice in various groups.Results:The HE and PAS staining results showed that the mice in control group had intact airway and alveolar structure,without infiltration of inflammatory cells or mucus secretion;compared with control group,there was a large number of infiltrating inflammatory cells in airway tissue of the mice in OVA group,and the inflammation and PAS scores were increased(P<0.01);compared with OVA group,the infiltration of inflammatory cells in airway tissue of the mice in JGYST group and OVA + JGYST group was decreased,and the inflammation and PAS scores were significantly decreased(P<0.01).The flow cytometry results showed that compared with control group,the numbers of eosinophils,Th2 cells,and DCs in lung tissue of the mice in OVA group were increased(P<0.05 or P<0.01),and the percentage of mature DCs and level of ROS were significantly increased(P<0.01);compared with OVA group,the numbers of eosinophils,Th2 cells,and DCs in lung tissue of the mice in JGYST group and OVA + JGYST group were decreased(P<0.01),and the percentage of mature DCs and level of ROS were significantly decreased(P<0.01).The RT-qPCR results showed that compared with control group,the expression levels of IL-4,IL-10,and TNF-α mRNA in lung tissue of the mice in OVA group were increased(P<0.01);compared with OVA group,the expression levels of IL-4 and TNF-α mRNA in lung tissue of the mice in JGYST group and OVA + JGYST group were decreased(P<0.01),while the expression level of IL-10 mRNA was increased(P<0.01).Conclusion:JGYST can alleviate the airway tissue inflammation and mucus secretion in the mice with allergic asthma,and its mechanism may be related to reducing the number of Th2 cells and DCs,decreasing the ROS level and expression level of proinflammatory cytokine,and increasing the expression level of anti-inflammatory cytokine.

Transglutaminase 2 (TGM2) is a ubiquitous multifunctional protein, which is related to the adhesion of different cells and tumor formation. Previous studies found that TGM2 is involved in the interaction between host cells and viruses, but the effect of TGM2 on the proliferation of influenza virus in cells has not been reported. To explore the effect of TGM2 during H1N1 subtype influenza virus infection, a stable MDCK cell line with TGM2 overexpression and a knockout cell line were constructed. The mRNA and protein expression levels of NP and NS1 as well as the virus titer were measured at 48 hours after pot-infection with H1N1 subtype influenza virus. The results showed that overexpression of TGM2 effectively inhibited the expression of NP and NS1 genes of H1N1 subtype influenza virus, while knockout of TGM2 up-regulated the expression of the NP and NS1 genes, and the expression of the NP at protein level was consistent with that at mRNA level. Virus proliferation curve showed that the titer of H1N1 subtype influenza virus decreased significantly upon TGM2 overexpression. On the contrary, the virus titer in TGM2 knockout cells reached the peak at 48 h, which further proved that TGM2 was involved in the inhibition of H1N1 subtype influenza virus proliferation in MDCK cells. By analyzing the expression of genes downstream of influenza virus response signaling pathway, we found that TGM2 may inhibit the proliferation of H1N1 subtype influenza virus by promoting the activation of JAK-STAT molecular pathway and inhibiting RIG-1 signaling pathway. The above findings are of great significance for revealing the mechanism underlying the interactions between host cells and virus and establishing a genetically engineering cell line for high-yield influenza vaccine production of influenza virus.
Animals ; Cell Proliferation ; Dogs ; Humans ; Influenza A Virus, H1N1 Subtype/genetics* ; Influenza, Human ; Madin Darby Canine Kidney Cells ; Protein Glutamine gamma Glutamyltransferase 2

OBJECTIVE：To study the improvement eff ects and its mech anism of Guiyuan decoction formula granules （GDFG） on model mice with decreased ovarian reserve （DOR）. METHODS ：Totally 42 female ICR mice whith with normal estrous cycle were randomly divided into control group ，model group ，estradiol valerate group （positive control ，0.15 mg/kg）and GDFG low-dose，medium-dose and high-dose groups （0.75，1.49，2.98 g/kg），with 7 mice in each group. Except for control group ，other groups were given cisplatin （3 mg/kg）intraperitoneally to establish DOR model. After modeling ，administration groups were given relevant medicine intragastrically；model group and control group were given normal saline intragastrically ，once a day ，for consecutive 4 weeks. After last administration ，ELISA assay was used to measure the serum levels of anti-Müllerian hormone （AMH）and follicle-stimulating hormone （FSH）in mice. Histopathological morphology of ovarian was observed by HE staining. Protein distribution of AMH receptor Ⅱ（AMHRⅡ）and Smad 4 in ovarian tissue were observed by immunohistochemistry. Protein expression of AMHR Ⅱ and Smad 4 were detected by Western blot assay. RESULTS ：Compared with control group ，theserum level of AMH ，the expression of AMHR Ⅱ and Smad 4 protein in ovarian tissue in model group were significantly decreased （P＜0.01），while the FSH level in serum was significantly increased （P＜0.01）；follicles were crumpled and lost nucleus ，ovarian interstitial were fibrosis ，luteum were loose ； AMHRⅡ and Smad 4 protein in ovarian tissue were mainly distributed in the follicle membrane and ovarian interstitial. Compared with model group ，the serum level of AMH ，the expression of AMHR Ⅱ and Smad 4 protein in ovarian tissue was increased significantly in GDFG groups （P＜0.01），while the serum level of FSH was decreased significantly （P＜0.05 or P＜0.01）；in ovarian tissue ，follicles at all levels could be found and follicle morphology was improved ，and no obvious nuclear loss and cumulus formation were found ；AMHRⅡ and Smad 4 protein were mainly distributed in the follicular nucleus （except for GDFG high-dose group) and the granular cell membrane （mainly distributed in the sinus follicles of GDFG medium-dose group ）；they were slightly distributed around the mature follicular nucleus or in corpus luteum. CONCLUSIONS ：GDFG can improve ovarian function of DOR model mice. The mechanism may be related with promoting serum level of AMH ，protein expression of AMHR Ⅱ and Smad 4，improving the distribution of AMHR Ⅱ and Smad 4 protein in ovarian granulosa cell membrane and follicular nucleus ， reducing FSH levels.