ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang （FFD） on mitochondrial function in the mouse model of myocardial fibrosis （MF）. MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups （n=10 per group）： control， model， low-dose， medium-dose， and high-dose （3.315， 6.63， and 13.26 g·kg^-1， respectively） FFD， and captopril （20 mg·kg^-1）. MF was induced by subcutaneous injection of isoproterenol （10 mg·kg^-1·d^-1） in other groups except the control group for 14 consecutive days， with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were measured by echocardiography. Serum levels of creatine kinase-MB （CK-MB）， cardiac troponin I （cTnI）， N-terminal pro-brain natriuretic peptide （NT-pro BNP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） levels were measured by biochemical assays. Reactive oxygen species （ROS） were detected by dihydroethidium （DHE） fluorescence staining. Hematoxylin-eosin （HE）， Masson's trichrome， and wheat germ agglutinin （WGA） staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy， adenosine triphosphate （ATP） colorimetric assay， and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit （p-AMPKα）， AMPKα， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， mitofusin 2 （MFN2）， pyruvate kinase M2 isoform （PKM2）， lactate dehydrogenase A （LDHA）， and hypoxia-inducible factor 1 alpha （HIF-1α） were analyzed by Western blot. ResultsCompared with the control group， the model group exhibited decreased LVEF and LVFS， increased heart weight index and heart weight-to-tibia length ratio （P<0.01）， elevated levels of myocardial injury markers （CK-MB， cTnI， and NT-pro BNP）， inflammatory cytokines （TNF-α， IL-1β， and IL-6）， and MDA， along with reduced SOD and GSH levels （P<0.01）. Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group （P<0.01）. Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling， crista disruption， decreased ATP content， and reduced red/green fluorescence ratio in the model group （P<0.01）. Western blot analysis demonstrated downregulation of p-AMPKα， PGC-1α， and MFN2 and upregulation of PKM2， LDHA， and HIF-1α in the model group （P<0.01）. Compared with the model group， treatment with FFD or captopril improved LVEF and LVFS， reduced heart weight index and heart weight-to-tibia length ratio （P<0.05， P<0.01）， lowered the serum levels of CK-MB， cTnI， NT-pro BNP， TNF-α， IL-1β， IL-6， and MDA， increased the SOD and GSH levels （P<0.05， P<0.01）， attenuated the myocardial fibrosis and cardiomyocyte hypertrophy （P<0.01）， and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio （P<0.05， P<0.01）. Furthermore， FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α （P<0.05， P<0.01）. ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis， thereby attenuating isoproterenol-induced myocardial fibrosis.

ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang （FFD） on mitochondrial function in the mouse model of myocardial fibrosis （MF）. MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups （n=10 per group）： control， model， low-dose， medium-dose， and high-dose （3.315， 6.63， and 13.26 g·kg^-1， respectively） FFD， and captopril （20 mg·kg^-1）. MF was induced by subcutaneous injection of isoproterenol （10 mg·kg^-1·d^-1） in other groups except the control group for 14 consecutive days， with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were measured by echocardiography. Serum levels of creatine kinase-MB （CK-MB）， cardiac troponin I （cTnI）， N-terminal pro-brain natriuretic peptide （NT-pro BNP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） levels were measured by biochemical assays. Reactive oxygen species （ROS） were detected by dihydroethidium （DHE） fluorescence staining. Hematoxylin-eosin （HE）， Masson's trichrome， and wheat germ agglutinin （WGA） staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy， adenosine triphosphate （ATP） colorimetric assay， and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit （p-AMPKα）， AMPKα， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， mitofusin 2 （MFN2）， pyruvate kinase M2 isoform （PKM2）， lactate dehydrogenase A （LDHA）， and hypoxia-inducible factor 1 alpha （HIF-1α） were analyzed by Western blot. ResultsCompared with the control group， the model group exhibited decreased LVEF and LVFS， increased heart weight index and heart weight-to-tibia length ratio （P<0.01）， elevated levels of myocardial injury markers （CK-MB， cTnI， and NT-pro BNP）， inflammatory cytokines （TNF-α， IL-1β， and IL-6）， and MDA， along with reduced SOD and GSH levels （P<0.01）. Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group （P<0.01）. Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling， crista disruption， decreased ATP content， and reduced red/green fluorescence ratio in the model group （P<0.01）. Western blot analysis demonstrated downregulation of p-AMPKα， PGC-1α， and MFN2 and upregulation of PKM2， LDHA， and HIF-1α in the model group （P<0.01）. Compared with the model group， treatment with FFD or captopril improved LVEF and LVFS， reduced heart weight index and heart weight-to-tibia length ratio （P<0.05， P<0.01）， lowered the serum levels of CK-MB， cTnI， NT-pro BNP， TNF-α， IL-1β， IL-6， and MDA， increased the SOD and GSH levels （P<0.05， P<0.01）， attenuated the myocardial fibrosis and cardiomyocyte hypertrophy （P<0.01）， and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio （P<0.05， P<0.01）. Furthermore， FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α （P<0.05， P<0.01）. ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis， thereby attenuating isoproterenol-induced myocardial fibrosis.

Objective:To explore the clinical characteristics, treatment and prognosis of hard metal lung disease (HMLD), and to provide a theoretical reference basis for the prevention, control and intervention of HMLD in China.Methods:In April 2024, literatures related to HMLD and giant cell interstitial pneumonia (GIP) published before March 31, 2024 were retrieved in China National Knowledge Infrastructure (CNKI), Wanfang, VIP database, Embase and PubMed. The search terms in Chinese and English included hard metal lung disease, cobalt, tungsten carbide, giant cell interstitial pneumonia, hard metal, etc. Literature was screened and data were extracted. A systematic review was conducted to analyze the clinical characteristics, imaging, pulmonary function, pathological features, treatment and prognosis of HMLD.Results:A total of 55 literatures were included, including 1 cohort study, 4 cross-sectional studies, 4 case series reports and 46 case reports, involving a total of 227 patients with HMLD and GIP. There were 174 male cases, 51 female cases, and 2 cases whose gender was not mentioned. The age was (43.9±13.4) years old, and the dust exposure time was 7 (4, 13) years. The chest images of the patients showed ground glass shadow, micro-nodule shadow, grid shadow, honeycomb shadow, consolidation shadow, etc. Pulmonary function test showed restrictive ventilation dysfunction with gas exchange disorder. The pathological manifestations of lung tissue were typical GIP, but there were also hypersensitivity pneumonitis, common interstitial pneumonia, diffuse alveolar damage, non-specific interstitial pneumonia, and even honeycomb lung. Clinical diagnosis and treatment evaluation were performed by combining the occupational exposure history of hard metal dust or cobalt-containing dust, clinical manifestations, imaging, lung function and histopathology. Treatment involved cessation of exposure, with glucocorticoids alleviating symptoms and improving imaging and pulmonary function.Conclusion:HMLD can be caused by hard metal dust exposure. The clinical symptoms of HMLD are not specific, and the pathology shows typical GIP or other pulmonary interstitial changes. The treatment involves cessation of exposure and administration of glucocorticoids, and the overall prognosis is good.

Objective:To explore the clinical characteristics, treatment and prognosis of hard metal lung disease (HMLD), and to provide a theoretical reference basis for the prevention, control and intervention of HMLD in China.Methods:In April 2024, literatures related to HMLD and giant cell interstitial pneumonia (GIP) published before March 31, 2024 were retrieved in China National Knowledge Infrastructure (CNKI), Wanfang, VIP database, Embase and PubMed. The search terms in Chinese and English included hard metal lung disease, cobalt, tungsten carbide, giant cell interstitial pneumonia, hard metal, etc. Literature was screened and data were extracted. A systematic review was conducted to analyze the clinical characteristics, imaging, pulmonary function, pathological features, treatment and prognosis of HMLD.Results:A total of 55 literatures were included, including 1 cohort study, 4 cross-sectional studies, 4 case series reports and 46 case reports, involving a total of 227 patients with HMLD and GIP. There were 174 male cases, 51 female cases, and 2 cases whose gender was not mentioned. The age was (43.9±13.4) years old, and the dust exposure time was 7 (4, 13) years. The chest images of the patients showed ground glass shadow, micro-nodule shadow, grid shadow, honeycomb shadow, consolidation shadow, etc. Pulmonary function test showed restrictive ventilation dysfunction with gas exchange disorder. The pathological manifestations of lung tissue were typical GIP, but there were also hypersensitivity pneumonitis, common interstitial pneumonia, diffuse alveolar damage, non-specific interstitial pneumonia, and even honeycomb lung. Clinical diagnosis and treatment evaluation were performed by combining the occupational exposure history of hard metal dust or cobalt-containing dust, clinical manifestations, imaging, lung function and histopathology. Treatment involved cessation of exposure, with glucocorticoids alleviating symptoms and improving imaging and pulmonary function.Conclusion:HMLD can be caused by hard metal dust exposure. The clinical symptoms of HMLD are not specific, and the pathology shows typical GIP or other pulmonary interstitial changes. The treatment involves cessation of exposure and administration of glucocorticoids, and the overall prognosis is good.

Objective:To analyze the correlation between peripheral blood eosinophil (EOS) level and clinical characteristics of patients with pneumoconiosis complicated with chronic obstructive pulmonary disease (COPD) .Methods:From January 2007 to November 2020, newly diagnosed patients with pneumoconiosis complicated with COPD in Beijing Chaoyang Hospital, were retrospectively analyzed. These patients were stratified into EOS<100 cells/μl group and EOS≥100 cells/μl group, taking 100 cells/μl as the cut-off value. Demographic characteristics, clinical symptoms, lung function and laboratory indexes were compared between the two groups.Results:The median EOS count of patients with pneumoconiosis complicated with COPD was 100 (40, 180) cells/μl. 50.2% (160/319) had blood eosinophil counts ≥100 cells/μl, and 11.0% (35/319) had blood eosinophil counts ≥300 cells/μl. In comparison with EOS<100 cells/μl group, EOS≥100 cells/μl group were older ( P=0.035), had higher body mass index ( P=0.008), and had lower forced respiratory volume in the first second ( P=0.017), had higher the ratio of residual volume to total lung volume ( P=0.010), and had lower diffusing capacity of the lung for carbon monoxide ( P=0.008). Arterial partial pressure of oxygen was significantly reduced in EOS≥100 cells/μl group ( P=0.039). The peripheral blood EOS count was negatively correlated with forced vital capacity, forced breathing volume in the first second, carbon monoxide diffusion, peak expiratory flow, and maximum mid expiratory flow as a percentage of expected values ( rs=-0.22, -0.18, -0.19, -0.19, -0.19, P=0.000, 0.001, 0.003, 0.008, 0.002), and positively correlated with the ratio of residual air volume to total lung volume ( rs=0.17, P=0.002) . Conclusion:There was a correlation between blood EOS count and pulmonary function parameters, can proide reference for the diagnosis and treatment of chnoric obstuctive pulmmory disease in clinical practice.

Objective:To analyze the correlation between peripheral blood eosinophil (EOS) level and clinical characteristics of patients with pneumoconiosis complicated with chronic obstructive pulmonary disease (COPD) .Methods:From January 2007 to November 2020, newly diagnosed patients with pneumoconiosis complicated with COPD in Beijing Chaoyang Hospital, were retrospectively analyzed. These patients were stratified into EOS<100 cells/μl group and EOS≥100 cells/μl group, taking 100 cells/μl as the cut-off value. Demographic characteristics, clinical symptoms, lung function and laboratory indexes were compared between the two groups.Results:The median EOS count of patients with pneumoconiosis complicated with COPD was 100 (40, 180) cells/μl. 50.2% (160/319) had blood eosinophil counts ≥100 cells/μl, and 11.0% (35/319) had blood eosinophil counts ≥300 cells/μl. In comparison with EOS<100 cells/μl group, EOS≥100 cells/μl group were older ( P=0.035), had higher body mass index ( P=0.008), and had lower forced respiratory volume in the first second ( P=0.017), had higher the ratio of residual volume to total lung volume ( P=0.010), and had lower diffusing capacity of the lung for carbon monoxide ( P=0.008). Arterial partial pressure of oxygen was significantly reduced in EOS≥100 cells/μl group ( P=0.039). The peripheral blood EOS count was negatively correlated with forced vital capacity, forced breathing volume in the first second, carbon monoxide diffusion, peak expiratory flow, and maximum mid expiratory flow as a percentage of expected values ( rs=-0.22, -0.18, -0.19, -0.19, -0.19, P=0.000, 0.001, 0.003, 0.008, 0.002), and positively correlated with the ratio of residual air volume to total lung volume ( rs=0.17, P=0.002) . Conclusion:There was a correlation between blood EOS count and pulmonary function parameters, can proide reference for the diagnosis and treatment of chnoric obstuctive pulmmory disease in clinical practice.

ObjectiveTo investigate the effects of Fangji Fulingtang on macrophage polarization and oxidative stress in the mouse model of myocardial fibrosis. MethodThe mouse model of myocardial fibrosis was established by subcutaneous injection of isoproterenol （ISO， 5 mg·kg^-1·d^-1）. Fifty C57BL/6J mice were randomly assigned into control （0.9% NaCl）， model （0.9% NaCl）， low- and high-dose （3.315 g·kg^-1·d^-1 and 13.26 g·kg^-1·d^-1， respectively） Fangji Fulingtang （FFD-L and FFD-H， respectively）， and metoprolol tartrate （Meto， 15 mg·kg^-1·d^-1） groups， with 10 mice each group. After 2 weeks of treatment， the heart appearance， cardiac weight index （CWI）， heart weight （HW）/tibia length （TL） ratio， and myocardial histopathological alterations were observed. Meanwhile， the serum levels of creatine kinase-MB （CK-MB）， transforming growth factor-β₁ （TGF-β₁）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-6， IL-10， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） were measured by enzyme-linked immunosorbent assay （ELISA）. The expression levels of CD86 and CD206 were observed by immunohistochemical staining. ResultCompared with the model group， the FFD-L， FFD-H， and Meto groups showed improved heart appearance， decreased CWI and HW/TL ratio （P<0.01）， lowered serum levels of CK-MB， TGF-β₁， TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， and elevated IL-10 level （P<0.05）. Furthermore， the three groups showed reduced infiltration of inflammatory cells， myocardial injury， collagen deposition， and myocardial fibrosis， decreased CD86， SOD， and GSH （P<0.01）， and increased CD206 and MDA （P<0.01）. ConclusionFangji Fulingtang can mitigate ISO-induced myocardial fibrosis by regulating macrophage polarization and oxidative stress.

Objective:To explore the clinical charecteristics, imaging features, therapy and prognosis of stroke in children, and provide help for clinical treatment.Methods:The clinical data of 49 children with stroke were collectedand retrospectively analyzed in the Children′s Hospital of Soochow University from January 1, 2019 to December 31, 2019.Results:A mong the 49 children with stroke, 35 were male and 14 were female, aged 1-178 (65.69 ± 55.22) months; the specific etiologies were cerebrovascular malformation, craniocerebral trauma, tumor, vitamin K deficiencies, infectious diseases, rheumatic immune diseases, hemophilia and congenital heart disease. The first symptoms of stroke were disturbance of consciousness, hemiplegia, convulsions, vomiting and headache. The arterial ischemic stroke (18 cases) were mainly caused by craniocerebral trauma and cerebrovascular malformation. The hemorrhagic stroke (31 cases) were mainly caused by arteriovenous malformation, vitamin K deficiency and tumor. The surgical rate in the arterial stroke group was significantly lower than that in the hemorrhagic stroke group.Conclusions:Traumatic cerebral infarction and intracranial arteriovenous malformation are the main causes of arterial ischemic stroke and hemorrhagic stroke in children. Early diagnosis and treatment can significantly improve prognosis.

Objective: To investigate the etiology, clinical features, treatment and outcome of nephrotic syndrome associated with chronic mercury poisoning. Methods: From June 2013 to April 2018, Beijing Chaoyang Hospital, Capital Medical University received 33 patients with chronic mercury-neutral nephrotic syndrome. The clinical manifestations, laboratory tests, treatment methods, and outcomes were analyzed. Results: Among the 33 patients, 27 patients had mercury exposure due to daily-life contact and the other 6 patients were caused by iatrogenic mercury. The symptom was characterized by typical nephrotic syndrome such as lower extremity edema and proteinuria at first onset. The treatment was based on mercury-removing treatment, 19 cases were treated with mercury removal alone, 16 cases were completely relieved; 10 cases were treated with mercury removal and glucocorticoids, all of which were completely relieved; 4 cases were treated with mercury removal, glucocorticoids and immunosuppressive agents, all complete remission; clinical complete remission rate is about 90.9% (30 cases in total) . Urinary mercury levels decreased the fastest between the first and second courses of mercury treatment, but the total amount of urine protein increased. As the amount of urinary mercury excreted increased, the total amount of urine protein decreased gradually (Z=2.86, P<0.01) . Conclusion The clinical features of chronic mercury-induced nephrotic syndrome are non-specific, easy to be misdiagnosed and missed. The treatment is mainly treated with mercury removal treatment. The prognosis is good. In severe cases, glucocorticoid therapy can be supplemented.

OBJECTIVETo carry out genetic testing for a family affected with pulmonary hypertension (PH) as the initial sign of hereditary hemorrhagic telangiectasia (HHT).

METHODSHigh throughput sequencing was performed to detect potential mutation in the coding regions of endoglin (ENG), activin receptor-like kinase 1 (ACVRL1) and mothers against decapentaplegic homolog 4 (SMAD4) genes.

RESULTSA pathogenic heterozygous c.814C>T (p.Gln272Ter) mutation of the ACVRL1 gene was identified in the proband. Her mother and two sons have carried the same mutation.

CONCLUSIONThe c.814C>T (p.Gln272Ter) mutation of the ACVRL1 gene probably underlies the disease in this family. Genetic testing should be recommended to HHT patient, in particular those with pulmonary hypertension.

Activin Receptors, Type II ; genetics ; Child ; Endoglin ; genetics ; Female ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Hypertension, Pulmonary ; etiology ; genetics ; Male ; Middle Aged ; Mutation ; Telangiectasia, Hereditary Hemorrhagic ; complications