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*

OBJECTIVES: To investigate the role and mechanism of Brahma-related gene 1 (Brg1) in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia (BPD) model. METHODS: Wild-type C57BL/6 and Brg1^f1/f1 mice were randomly divided into four groups: wild-type control, wild-type BPD, Brg1^f1/f1 control, and Brg1^f1/f1 BPD (n=5 each). Immortalized mouse pulmonary alveolar type 2 cells (imPAC2) were cultured, and Brg1 gene was knocked down using lentivirus transfection technology. Cells were divided into three groups: control, empty vector, and Brg1 knockdown. Hematoxylin and eosin staining and immunofluorescence were used to detect pathological changes in mouse lung tissue. Western blot and real-time fluorescent quantitative PCR were used to measure Brg1 protein and mRNA expression levels in mouse lung tissue. Western blot and immunofluorescence were used to detect the expression of homeodomain-containing protein homeobox (HOPX), surfactant protein C (SPC), and Wnt/β-catenin signaling pathway proteins in mouse lung tissue and imPAC2 cells. The CCK8 assay was used to assess the proliferation of imPAC2 cells, and co-immunoprecipitation was performed to verify the interaction between Brg1 and β-catenin proteins in imPAC2 cells. RESULTS: Compared to the Brg1^f1/f1 control group and wild-type BPD group, the Brg1^f1/f1 BPD group showed increased alveolar diameter and SPC protein expression, and decreased relative density of pulmonary vasculature and HOPX protein expression (P<0.05). Compared to the control group, the Brg1 knockdown group showed increased cell proliferation ability, protein expression levels of SPC, Wnt5a and β-catenin, and β-catenin protein fluorescence intensity, along with decreased HOPX protein expression (P<0.05). An interaction between Brg1 and β-catenin proteins was confirmed. CONCLUSIONS The Brg1 gene may promote the proliferation of alveolar type 2 epithelial cells by regulating the Wnt/β-catenin signaling pathway, thus influencing the occurrence and development of BPD.
Animals ; DNA Helicases/genetics* ; Transcription Factors/genetics* ; Wnt Signaling Pathway/physiology* ; Nuclear Proteins/genetics* ; Mice ; Bronchopulmonary Dysplasia/etiology* ; Mice, Inbred C57BL ; beta Catenin/physiology* ; Disease Models, Animal ; Cell Proliferation ; Lung/pathology* ; Male

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Paraganglioma（PGL）is an extra-adrenal catecholamine-secreting endocrine tumor. We reported a young female patient who was admitted to the hospital with right flank pain and diagnosed with right retroperitoneal PGL with Mayo Ⅳ inferior vena cava tumor thrombus（double tumor thrombus）. After multidisciplinary consultation，right retroperitoneal PGL resection，right nephrectomy，inferior vena cava Mayo Ⅳ tumor thrombus resection and reconstruction were performed. Postoperative pathology showed that the primary tumor and inferior vena cava tumor thrombus was consistent with PGL. Genetic testing revealed a heterozygous germline nonsense mutation at c.69_70delinsTT（p.Q24*）locus of the SDHB gene in the patient. His mother was a carrier of the gene，but his father and sister did not carry the mutation. The patient recovered smoothly after surgery.

Objective:To analyze the safety and efficacy of multi-vessel minimally invasive cardiac surgery-coronary artery bypass graft(MICS-CABG) through perioperative angiography results and complications.Methods:Clinical data of 1 073 patients who underwent multi-vessel MICS-CABG surgery at Peking University Third Hospital from December 2015 to June 2024 were collected using an ambispective cohort study. Among them, 745 were males(69.4%), with a median age of 65 years(58, 71), and a median ejection fraction of 0.66(0.56, 0.71). Double-vessel or triple-vessel lesions accounted for 932 cases(86.9%), while left main lesions were present in 449 cases(41.8%). The primary outcome was the evaluation of graft patency based on perioperative angiography or coronary artery computed tomography angiography results, while major cardiovascular adverse events during the perioperative period, surgical complications, and other surgical information were secondary outcomes. The clinical efficacy of multi-vessel MICS-CABG was evaluated.Results:In this study, the median number of grafts was 3, and complete revascularization was performed in 1 006 cases(93.8%); total arterial revascularization was performed in 308 cases(28.6%). Perioperative mortality was 11 cases(1.0%), and the main adverse cardiovascular and cerebrovascular events(MACCE) was 50 cases(4.8%). Three cases(0.3%) had poor wound healing, and 79 patients(7.4%) required transfusion. Postoperative coronary angiography was performed in 907 patients(84.5%) and coronary CTA was performed in 52 patients(4.8%), for an overall review rate of 89.4%(959/1073). The overall patency rate of the bridge vessel was 96.9%, and the patency rate of the left internal mammary artery was 98.2%.Conclusion:Multi-vessel MICS-CABG demonstrates excellent perioperative safety and is capable of achieving complete revascularization for the 3 regions of the heart. The quality of the anastomosis and the postoperative patency rate of the grafts is satisfactory.

Objective:To investigate the longitudinal patterns and influencing factors of platelet counts among healthy adults in Sichuan Province from 2010 to 2021, and to inform the establishment of region-specific reference intervals for platelet counts.Methods:This study is a retrospective study. A total of 7 808 healthy adults who underwent annual physical examinations at West China Hospital, Sichuan University, between January 2010 and December 2021 were included. All participants were permanent Chengdu residents and completed consecutive complete blood count tests. Group-based trajectory modeling (GBTM) was used to identify distinct trajectories of platelet count over the ten-year period. One-way analyses were then conducted to compare baseline demographic characteristics (sex and age) among the different trajectory groups.Results:Among 7 808 participants, 4 589 (58.8%) were male and 3 219 (41.2%) were female. Four platelet count trajectories were identified by GBTM: steadily increasing group [27.4% (2 139/7 808)], early increase-plateau group [44.1% (3 445/7 808)], early decrease-subsequent increase group [5.4% (422/7 808)], and steadily decreasing group [23.1% (1 802/7 808)], with an average growth rate of 3.3%, 1.6%, 0.7%, and -0.6%, respectively. There were statistically significant differences in both sex and age distributions among the four trajectory groups. Sex-distribution differed significantly across the four trajectory groups ( χ2=73.3, P<0.001). The male proportions in the four trajectory groups were 59.6% (1 275/2 139), 62.8% (2 165/3 445), 48.1% (203/422), and 52.5% (946/1 802), respectively. The baseline ages were 45 (36, 55), 43 (35, 53), 50 (40, 60), and 47 (39, 58) years, respectively (H=121.0, P<0.001). Conclusions:Healthy adults in Sichuan Province exhibit four longitudinal trajectories of platelet counts: steadily increasing, early increase-plateau, early decrease-subsequent increase, and steadily decreasing. The two trajectories characterized by rising platelet counts (steadily increasing group and early increase-plateau group) exhibited higher male predominance and lower median ages, whereas the early decrease-subsequent increase group and the steadily decreasing group exhibited lower male proportions and higher median ages. Therefore, while establishing reference intervals and developing health management strategies for platelet counts, it is essential to account for the sex, age characteristics and the population′s dynamic changes.

Paraganglioma（PGL）is an extra-adrenal catecholamine-secreting endocrine tumor. We reported a young female patient who was admitted to the hospital with right flank pain and diagnosed with right retroperitoneal PGL with Mayo Ⅳ inferior vena cava tumor thrombus（double tumor thrombus）. After multidisciplinary consultation，right retroperitoneal PGL resection，right nephrectomy，inferior vena cava Mayo Ⅳ tumor thrombus resection and reconstruction were performed. Postoperative pathology showed that the primary tumor and inferior vena cava tumor thrombus was consistent with PGL. Genetic testing revealed a heterozygous germline nonsense mutation at c.69_70delinsTT（p.Q24*）locus of the SDHB gene in the patient. His mother was a carrier of the gene，but his father and sister did not carry the mutation. The patient recovered smoothly after surgery.

Objective:To analyze the safety and efficacy of multi-vessel minimally invasive cardiac surgery-coronary artery bypass graft(MICS-CABG) through perioperative angiography results and complications.Methods:Clinical data of 1 073 patients who underwent multi-vessel MICS-CABG surgery at Peking University Third Hospital from December 2015 to June 2024 were collected using an ambispective cohort study. Among them, 745 were males(69.4%), with a median age of 65 years(58, 71), and a median ejection fraction of 0.66(0.56, 0.71). Double-vessel or triple-vessel lesions accounted for 932 cases(86.9%), while left main lesions were present in 449 cases(41.8%). The primary outcome was the evaluation of graft patency based on perioperative angiography or coronary artery computed tomography angiography results, while major cardiovascular adverse events during the perioperative period, surgical complications, and other surgical information were secondary outcomes. The clinical efficacy of multi-vessel MICS-CABG was evaluated.Results:In this study, the median number of grafts was 3, and complete revascularization was performed in 1 006 cases(93.8%); total arterial revascularization was performed in 308 cases(28.6%). Perioperative mortality was 11 cases(1.0%), and the main adverse cardiovascular and cerebrovascular events(MACCE) was 50 cases(4.8%). Three cases(0.3%) had poor wound healing, and 79 patients(7.4%) required transfusion. Postoperative coronary angiography was performed in 907 patients(84.5%) and coronary CTA was performed in 52 patients(4.8%), for an overall review rate of 89.4%(959/1073). The overall patency rate of the bridge vessel was 96.9%, and the patency rate of the left internal mammary artery was 98.2%.Conclusion:Multi-vessel MICS-CABG demonstrates excellent perioperative safety and is capable of achieving complete revascularization for the 3 regions of the heart. The quality of the anastomosis and the postoperative patency rate of the grafts is satisfactory.

Objective:To investigate the longitudinal patterns and influencing factors of platelet counts among healthy adults in Sichuan Province from 2010 to 2021, and to inform the establishment of region-specific reference intervals for platelet counts.Methods:This study is a retrospective study. A total of 7 808 healthy adults who underwent annual physical examinations at West China Hospital, Sichuan University, between January 2010 and December 2021 were included. All participants were permanent Chengdu residents and completed consecutive complete blood count tests. Group-based trajectory modeling (GBTM) was used to identify distinct trajectories of platelet count over the ten-year period. One-way analyses were then conducted to compare baseline demographic characteristics (sex and age) among the different trajectory groups.Results:Among 7 808 participants, 4 589 (58.8%) were male and 3 219 (41.2%) were female. Four platelet count trajectories were identified by GBTM: steadily increasing group [27.4% (2 139/7 808)], early increase-plateau group [44.1% (3 445/7 808)], early decrease-subsequent increase group [5.4% (422/7 808)], and steadily decreasing group [23.1% (1 802/7 808)], with an average growth rate of 3.3%, 1.6%, 0.7%, and -0.6%, respectively. There were statistically significant differences in both sex and age distributions among the four trajectory groups. Sex-distribution differed significantly across the four trajectory groups ( χ2=73.3, P<0.001). The male proportions in the four trajectory groups were 59.6% (1 275/2 139), 62.8% (2 165/3 445), 48.1% (203/422), and 52.5% (946/1 802), respectively. The baseline ages were 45 (36, 55), 43 (35, 53), 50 (40, 60), and 47 (39, 58) years, respectively (H=121.0, P<0.001). Conclusions:Healthy adults in Sichuan Province exhibit four longitudinal trajectories of platelet counts: steadily increasing, early increase-plateau, early decrease-subsequent increase, and steadily decreasing. The two trajectories characterized by rising platelet counts (steadily increasing group and early increase-plateau group) exhibited higher male predominance and lower median ages, whereas the early decrease-subsequent increase group and the steadily decreasing group exhibited lower male proportions and higher median ages. Therefore, while establishing reference intervals and developing health management strategies for platelet counts, it is essential to account for the sex, age characteristics and the population′s dynamic changes.

Objective To analyze the expression and detection significance of community acquired respiratory distress syndrome(CARDS)toxin in bronchoalveolar lavage fluid(BALF)in children with severe Mycoplasma pneumoniae pneumonia(SMPP).Methods The BALF samples of children diagnosed with Mycoplasma pneumoniae pneumonia(MPP)were collected from the Department of Pulmonology,Children's Hospital Affiliated to Capital Institute of Pediatrics from August 2021 to April 2022,the relative expression of CARDS toxins was determined by quantitative realtime polymerase chain reaction(qPCR).The patients were divided into SMPP group and non-SMPP group(control group).The relative expression of CARDS toxin and other clinical indicators were compared between the two groups.The risk factors of SMPP were analyzed.The predictive value of the indicators was analyzed using receiver operating characteristic(ROC)curves.Results ①The relative expression level of CARDS toxin(Z=-6.151),D-dimer(Z=-5.102)and lactate dehydrogenase(LDH)(Z=-6.337)in SMPP group were significantly higher than those in control group(P<0.001).The white blood cell(Z=-2.155),neutrophil ratio(t=2.988)and C-reactive protein(CRP)(Z=-3.360)were higher than those in control group(P<0.05).②The relative expression of CARDS toxin was positively correlated with serum LDH(r=0.258,P<0.05).③Binary Logistic regression analysis showed that fever time(OR=1.271,95% CI:1.079-1.497),LDH(OR=1.011,95% CI:1.005-1.017)and CARDS toxin(OR=6.210,95% CI:2.646-14.577)were risk factors for SMPP.Conclusion CARDS toxin was closely related to MPP disease,and was significantly increased in SMPP group.CARDS toxin was one of the independent risk factors for SMPP and positively correlated with serum LDH level.It can be used as a good indicator to evaluate the condition,combined with fever time and LDH has clinical significance.