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ObjectiveTo observe the effect of Scutellariae Radix-Coptidis Rhizoma on plaque stability in atherosclerotic （AS） mice and to explore its possible mechanism of action based on the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa B （NF-κB） signaling pathway. MethodTen normal C57BL/6J mice were used as the normal group， and the same strain of ApoE knockout （ApoE-/-） mice were fed with a high-fat diet for 12 weeks to construct an atherosclerosis model. Mice were randomly divided into five groups， namely the model group， the atorvastatin group， and the Scutellariae Radix-Coptidis Rhizoma low-， medium-， and high-dose groups， with ten mice in each group. Then normal and model groups were given equal volume of saline gavage， and the low-， medium-， high-dose Scutellariae Radix-Coptidis Rhizoma groups were given 1.95， 3.9， 7.8 g·kg-1 of the drug by gavage for 8 weeks， respectively. The general state of mice was observed. Hematoxylin-eosin staining was utilized to observe the pathology of aortic root plaques and calculate the percentage of plaque area. Masson staining and oil red O staining combined with immunohistochemistry of F4/80 and α-SMA were used to detect the plaque components of aortic root plaques and calculate the plaque vulnerability index. Enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）. Western blot was applied to detect the protein expression levels of matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， TLR4， MyD88， NF-κB p65， and phosphorylation （p） -NF-κB p65 in the aortic tissues of mice in each group. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） assay was employed to detect the expression levels of MMP-2， MMP-9， TLR4， and MyD88， NF-κB p65 mRNA. ResultCompared with the model group， the general state of the mice in each medication group was improved， and no obvious side effects were observed. Compared with the model group， the percentage of plaque area in the aortic root of AS mice was significantly reduced in the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. The content of collagen fibers and smooth muscle cells in the plaques of the high-dose Scutellariae Radix-Coptidis Rhizoma group was significantly increased （P<0.01）， and the content of lipids and macrophages was significantly reduced （P<0.05）， the plaque vulnerability index of each dose group of Scutellariae Radix-Coptidis Rhizoma was significantly reduced， with significant reduction of the medium- and high-dose groups （P<0.01）. MMP-2 and MMP-9 protein and mRNA expression levels in aortic tissues were significantly reduced in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. The serum levels of TNF-α and IL-6 were significantly reduced in AS mice in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. In the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups， the levels of TLR4， MyD88 protein， and mRNA expression in aortic tissues were significantly reduced （P<0.05）， and the level of NF-κB p65 phosphorylation in aortic tissues was significantly reduced （P<0.05）. ConclusionScutellariae Radix-Coptidis Rhizoma may play an anti-inflammatory and stabilizing role by inhibiting the TLR4/MyD88/NF-κB signaling pathway.
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ObjectiveTo investigate the therapeutic effect of Scutellariae Radix-Coptidis Rhizoma （SRCR） on atherosclerosis （AS） in mice and the effect of SRCR on macrophage pyroptosis in plaques via NOD-like receptor thermal protein domain-associated protein 3 （NLRP3） inflammasomes. MethodApoE-/- mice were fed with a high-fat diet for the modeling of AS and randomized into model， atorvastatin （5 mg·kg-1）， and low-， medium-， and high-dose （1.95， 3.9， 7.8 g·kg-1， respectively） SRCR groups. Normal C57BL/6J mice were selected as the control group. After 8 weeks of administration， hematoxylin-eosin staining was used to observe the pathological status of the aortic plaque. The lipid accumulation in aortic plaque was observed by oil red O staining. The serum levels of total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） in mice were measured. Immunofluorescence double staining was employed to detect the co-localized expression of EGF-like module-containing mucin-like hormone receptor-like 1 （EMR1）/NLRP3 and EMR1/gasdermin D （GSDMD）. The serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of NLRP3， apoptosis-associated speck-like protein （ASC）， Caspase-1， cleaved Caspase-1， GSDMD， N-terminus of GSDMD （GSDMD-NT）， pro-IL-1β， IL-1β， and IL-18 were determined by Western blot， and the mRNA levels of NLRP3， ASC， Caspase-1， GSDMD， IL-1β， and IL-18 were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the control group， the model group showed obvious plaques， elevated serum levels of TG， TC， LDL-C， IL-1β， and IL-18 （P<0.01）， lowered serum level of HDL-C （P<0.01）， and up-regulated expression of NLRP3 inflammasomes and molecules related to pyroptosis in the aortic plaques （P<0.01）. Compared with the model group， SRCR， especially at the medium and high doses， alleviated the plaque pathology， reduced the lipid content in plaques （P<0.05， P<0.01）， recovered the serum lipid levels （P<0.05）， reduced the macrophage recruitment （P<0.01）， activation of NLRP3 inflammasomes， and pyroptosis in aortic root plaques （P<0.05）， lowered the serum IL-1β and IL-18 levels （P<0.01）， and down-regulated the protein levels of NLRP3， ASC， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-NT， pro-IL-1β， IL-1β， and IL-18 （P<0.05） and the mRNA levels of NLRP3， ASC， Caspase-1， GSDMD， IL-1β， and IL-18 in the aortic tissue （P<0.05）. ConclusionSRCR exerts a therapeutic effect on high-fat diet-induced AS in mice by inhibiting the activation NLRP3 inflammasomes and reducing the pyroptosis of macrophages in plaques.
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Objective:To analyze the operative outcomes and postoperative pathological features of retroperitoneal leiomyosarcoma(RPLMS) undergoing surgeries.Methods:Medical records of RPLMS patients admitted to Peking University International Hospital from Jan 2015 through Dec 2020 were retrospectively reviewed.Results:Ninety-seven patients undergoing resectional surgeries were included in the study. Of whom, 49 cases were primary RPLMS. Others were recurrent sarcomas or sarcomas with incomplete resection in the first surgical intentions. The most frequent symptoms were abdominal pain and distention (30 cases) as well as lower back pain (23 cases). All patients underwent resectional surgeries with a R 0/R 1 rate of 84.5%. Sixty-four cases received extended surgeries with combined organs resection. External iliac artery resection with reconstruction were performed on 2 cases. And 19 patients underwent partial IVC resection in combination of sarcoma resection. The general postoperative morbidity was 26.8%, including 4 intestinal fistulas, 1 pancreatic fistula, 1 vesicovaginal fistula, 1 urinary fistula, 1 biliary fistula, 2 abdominal major bleeding, 7 IVC thrombosis, 3 gastroplegiaetc. One patient deceased within post-operative 30 d due to massive bleeding.Pathology found that spindle and pleomorphic cell types were most common subtypes of RPLMS. Conclusions:Surgery remains the mainstay in the treatment of RPLMS which often presents with atypical symptoms. Extended surgeries combining with multiple organ and major vascular resections could be only suggested in experienced sarcoma centers due to high risk of severe postoperative complications.
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Objective@#To improve the diagnostic accuracy of transthoracic echocardiography (TTE) by analyzing its limitations in diagnosing partial anomalous pulmonary venous drainage (PAPVD).@*Method@#This was a retrospective analysis of PAPVD patients seen at the Children′s Hospital of Fudan University from October 1 2006 to October 1 2016. The echocardiographic data were compared to findings on multi-slice spiral CT (MSCT), cardiac catheterization or surgery. The echocardiography machines used were Philip IE33, GE Vivid 7 and Vivid i with frequency ranging from 5.0 MHz to 7.5 MHz. The cardiac structure was analyzed according to Van Praagh segments.@*Result@#A total of 43 cases of PAPVD were enrolled, male∶ female ratio 20∶23 with average age (27.9±21.4) months. Among them, 3 cases were simple PAPVD and 40 cases had other associated congenital heart diseases. TTE was successful in diagnosing 29 cases (67%) while 14 cases were missed. The diagnostic rate for right pulmonary vein drainage into superior vena cava, right atrium, inferior vena cava were 5/10, 17/20, and 3/5 respectively while left pulmonary vein drainage into left innominate vein was only 1/4. Added TTE images to re-exam the 9 of the 14 missed cases, 5 cases of abnormal drainage from right superior pulmonary vein were diagnosed, while 4 cases of drainage from right lower or left pulmonary vein were only picked up by indirect signs.@*Conclusion@#The distance of the pulmonary veins from the routine ultrasound view and the possibility of branch number variation may limit the accuracy of TTE in diagnosing PAPVD, especially for drainage from right lower and left pulmonary vein. But TTE is still the preferred diagnostic method. The diagnostic rate could be increased by paying special attention to non-routine views including the suprasternal fossa, the right parasternal and subcostal area.
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Objective To follow up the changes of postnatal cardiac sizes and function in infants of mothers with gestational diabetes mellitus (GDM). Methods Eighteen GDM mothers with euglycemia (GDM group) and 24 gestational age-matched normal pregnant women (control group),having prenatal examination and delivered in Women's Hospital of Fudan University from January to August in 2007, received fetal echocardiographic examination in late pregnancy. Infants of these GDM mothers and 24 age-matched healthy infants of normal pregnancy (control group) received sonographic follow up. Cardiac sizes and function were evaluated and compared. Results At birth, there were six (33.3%) infants of large for gestational age (LGA) and 12(66.7%) appropriate for gestational age(AGA) in GDM group, while in the control group, there were two LGA (8. 3%) and 22(91.7%)AGA infants (x2 =3. 840, P= 0. 05). Both the interventricular septum and left ventricular walls in GDM fetuses were thicker than in control fetuses (P ＜ 0.05). No increase in the thickness of ventricular walls was observed till infantile period. However, the end-systolic thickness of left ventricular walls in LGA infants was still larger than in control infants [(4.55 ± 0.37) mm vs (4. 13±0.39)mm, P＜0. 05], and end-diastolic left ventricular long-diameters were also larger [(37. 3±2.3) mm vs (34.6±2.6) mm] (P＜0. 05). In GDM fetuses, the peak velocities of aorta and pulmonary artery and left cardiac output were higher than in the controls (P＜ 0. 01 ), and right/left cardiac outputs ratios were lower (1.198±0.206 vs 1. 430±0. 321, t= -2.668,P=0. 011). Till infantile period, only right/left cardiac outputs ratios in AGA infants of GDM group were larger than in controls (P＜0. 05). GDM fetuses' left atrial shortening fraction and tricuspid E/A ratios were smaller (P＜0. 05). In infantile period, only left atrial shortening fraction in GDM infants was still smaller than in controls (0. 356 ± 0. 040 vs 0. 386 ± 0. 041, t = - 2. 332, P = 0. 025). Left and right ventricular Tei index in GDM fetuses were 0. 482±0. 129 and 0. 414±0. 094, both larger than those of control fetuses (0. 309 ± 0. 074 and 0. 283 ± 0. 072) (t = 5. 075 and 5. 129, P = 0. 000 ). Till infantile period they both became significantly lower and no differences were found among LGA, AGA and control infants. Conclusions The cardiac sizes and function at 2-3 months of age, in infants of GDM mothers with good glucose control, became better than that in uterus.