Five new terpenoids, including two vibsane-type diterpenoids (1, 2) and three iridoid allosides (3-5), together with eight known ones, were isolated from the leaves and twigs of Viburnum odoratissimum var.sessiliflorum. Their planar structures and relative configurations were determined by spectroscopic methods, especially 2D NMR techniques. The sugar moieties of the iridoids were confirmed as β-D-allose by GC analysis after acid hydrolysis and acetylation. The absolute configurations of neovibsanin Q (1) and dehydrovibsanol B (2) were determined by quantum chemical calculation of their theoretical electronic circular dichroism (ECD) spectra and Rh₂(OCOCF₃)₄-induced ECD analysis. The anti-inflammatory activities of compounds 1, 3, 4, and 5 were evaluated using an LPS-induced RAW264.7 cell model. Compounds 3suppressed the release of NO in a dose-dependent manner, with an IC₅₀ value of 55.64 μmol·L^-1. The cytotoxicities of compounds 1-5 on HCT-116 cells were assessed and the results showed that compounds 2 and 3 exhibited moderate inhibitory activities with IC₅₀ values of 13.8 and 12.3 μmol·L^-1, respectively.
Terpenes/pharmacology* ; Viburnum/chemistry* ; Molecular Structure ; Diterpenes/chemistry* ; Plant Leaves/chemistry*

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

OBJECTIVE To study the regulator y mech anism of glaucocalyxin A （GLA） on autophagy and apoptosis of HCCLM3 hepatocellular carcinoma cells. METHODS HCCLM3 cells were taken ，and control group ，GLA 2.5 μg/mL group，GLA 5 μg/mL group and GLA 10 μg/mL group were mainly set according to different experimental purposes. In control group，only complete medium was added ；in each administration group ，complete medium containing the corresponding final concentration of GLA was added. Cell cycle distribution and apoptosis were detected by flow cytometry ；mitochondrial morphology and autophagy were observed by transmission electron microscope （only control group ，GLA 5 μg/mL group）；JC-1 staining and fluorescence inverted microscope were used to observe and detect the mitochondrial membrane potential of the cells ；Western blot assay was used to detect the protein expression of Bcl- 2， Bax， Beclin1 and cleaved caspase- 3 proteins in the cells ； the co-immunoprecipitation method was used to detect the binding and dissociation of Bcl- 2 and Beclin 1（only GLA 5 μg/mL group， GLA 10 μg/mL group）. RESULTS Compared with control group ，GLA 5 μg/mL and GLA 10 μg/mL could induce a significant arrest of the cell cycle in the G 2-M phase for HCCLM 3，a significant decrease in mitochondrial membrane potential ，an increase in apoptosis as well as significant promotion of the protein expression of Bax ，cleaved caspase- 3 and Beclin 1，and significant inhibition of the protein expression of Bcl- 2（P＜0.01）. GLA 5 μg/mL also significantly changed mitochondrial morphology and increased autophagosomes. The results of co-immunoprecipitation showed that compared with GLA 5 μg/mL，GLA 10 μg/mL could enhance the binding of Bcl- 2 and Beclin 1. CONCLUSIONS GLA can regulate the autophagy and apoptosis of HCCLM 3 cells by Bcl-2/Beclin1 target. The effect is closely related to the dose of GLA.

Objective:To clarity the clinical features of juvenile dermatomyositis (JDM) with positive anti-melanoma differentiation associated gene 5 (MDA5) antibody.Methods:Retrospective study.Clinical data of 11 anti-MDA5 autoantibody-positive JDM patients in the Department of Rheumatology and Immunology, Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2016 to January 2019 were retrospectively recruited for analyzing their clinical characteristics, pulmonary imaging and pulmonary function, thus summarizing treatment experiences.Results:A total of 11 children with anti-MDA5 autoantibody-positive JDM were recruited, involving 2 males and 9 females, with the average onset age of 1-13 (5.8±4.2) years.Clinical manifestations included rash in 11 cases (100.0%), arthritis in 5 cases (45.5%), and myasthenia in 4 cases (36.4%). Muscle enzyme elevated in 10 cases (90.9%) and serum ferritin (SF) elevated in 9 patients (81.8%). Ten cases (90.9%) showed interstitial lung disease (ILD), manifesting as ground glass opacity at subpleural area on CT scans, restrictive ventilation and decreased diffusion function on lung function test, while respiratory symptoms were absent.All patients were treated with glucocorticoid combined with immunosuppressor.Case 2 developed into rapid progressive pulmonary interstitial disease (RPILD), and died of respiratory failure 2 months later.The remaining was followed up for 1-2 years, and the ILD was relieved.Conclusions:All recruited children with anti-MDA5 autoantibody-positive JDM presented typical rash, and mild muscle weakness with a greater tendency to arthritis.Chinese pediatric patients are prone to complicate with ILD with no respiratory symptoms, but ground glass opacity at subpleural area on CT, and restrictive ventilation and decreased diffusion function on lung function test can be detected.Elevated SF is associated with the development of ILD.Glucocorticoid combined with immunosuppressive therapy is effective to JDM with ILD, but ineffective for RPILD.The mortality of anti-MDA5 autoantibody-positive JDM is high without an effective treatment.

Objective:To explore the relationship between drug evidence and core prescription for depression.Methods:We retrieved literature of TCM for depression from CNKI, VIP and Wangfang databases to November 2019, 30th as well as there cords from Ancient and Modern Medical Records Cloud Platform (V 1.5). The Excel 2010 was used to establish the standardized database of medical records. After the standardization of medicines, Ancient and Modern Medical Records Cloud Platform (V1.5) statistics methodswere used for association rules analysis, complex networks, and analysis of drugs’ frequency, medical characteristics, core prescription drugs.Results:A total of 632 effective prescriptions were included, involving a total of 527 drugs. The results of frequency of herbs showed that 23 kinds of high-frequency herbs were obtained. Bupleuri Radix was the most frequently used medicine. Most herbs are warm or flat, with pungent, sweet and bitter in taste, belonging to the lung, liver, heart and spleen meridians. A total of 25 drug-pair association and 13 TCM association were obtained by association rule analysis. Conclusions:TCM treatment for depression is mainly based on soothing the liver and regulating qi, clearing the heart and calming the nerves. Bupleuri Radix, Curcumae Radix, Paeoniae Radix Alba, Chuanxiong Rhizoma, Ziziphi Spinosae Semen are the basic prescriptions. Angelicae Sinensis Radix, Ophiopogonis Radix, Albiziae Cortex, Polygalae Radix, Poria are used as reference.

Objective:To investigate the clinical features, diagnosis and treatment of systemic juvenile idiopathic arthritis (SJIA) complicated with macrophage activation syndrome (MAS).Methods:From January 1st, 2018 to January 1st, 2020, 7 cases of SJIA-MAS were diagnosed. Their clinical and laboratory data were collected and summarized.Results:In these 7 cases, 2 were males and 5 were females, the ratio of male to female was 2∶5. The age range was 11 months to 2 years old. The course of disease was 14 to 32 days. The clinical manifestations included fever and rash in 7 without arthritis; hepatomegaly, splenomegaly and lymphadenopathy in 7; hematological involvement in 7; nervous system involvement in 2; digestive system involvement in 7; respiratory system involvement in 7; cardiovascular involvement in 3. White blood cell was decreased in 1 case, platelet was decreased in 1 case and hemoglobin was decreased in 7 cases. Ferritin, triglyceride, alanine transaminas and aspartate aminotransferase were increased in 7 cases, fibrinogen was significantly decreased in 7 cases, and direct bilirubin was increased in 4 cases. IL-2R was significantly increased. Hemophagocytosis was observed in bone marrow of 4 cases. Cerebrospinal fluid protein was 2 005 mg/L in 1 case. All the 7 cases were tested for exon genes, and no pathogenic mutation was found. All of the 7 cases showed lung lesions in chest CT scan. Multiple demyelinating lesions were found in 1 case by head magnetic resonance imaging. One case was treated with high-dose intravenous methylprednisolone combined with IL-6 receptor antagonist(tocilizumab). The other 6 cases were treated with high-dose intravenous methylprednisolone combined with cyclosporine A (CsA). Two cases were treated with Janus kinases inhibitor(tofacitinib). After treatment, 7 cases got relieved, no death, no recurrence oocurred during the follow-up.Conclusion:Acute onset, multiple organ involvement and no joint inflammation are prominent in MAS of infants and toddlers. High fever, proressive reduction of blood cells and increase of SF are significant in SJIA-MAS. High dose glucocorticoid combined with CsA can benefit in most cases, and some severe cases need to be treated with biological agents.

Objective:To summarize the clinical characteristics of children with rheumatic disease combined with endocrine disorder.Methods:A retrospective analysis was performed on the clinical data, including sex, age, clinical presentation, laboratory tests, treatment and outcome, of 13 patients with rheumatic diseases combined with endocrine disorder, who were admitted to our department in Children′s Hospital, Capital Institute of Pediatrics from January 2014 to December 2020.Results:Among the 13 cases, 3 were males and 10 were females, without family history. Their age was (10±4) years. And the average course of disease was 4.1 months. Eight of them were diagnosed with systemic lupus erythematosus (JSLE), 2 with juvenile idiopathic arthritis (JIA), 1 with childhood vasculitis, 1 with juvenile-onset systemic sclerosis (JSSc) and 1 had juvenile dermatomyositis (JDM). Regarding the initial presentation, 10 cases had symptoms of rheumatic disease, 2 had polydipsia and polyuria, and 1 had goiter. All the 13 patients had multiple system involvement. Regarding endocrine disorder, 10 had thyroiditis or subclinical thyroiditis, 4 had diabetes mellitus and one had both thyroid and pancreas involvement. Thyroid stimulating hormone in 10 patient with thyroid involvment was 19.6 (5.2-34.0) mU/L, and their total thyroxine was 75.3 (45.2-105.4) nmol/L. Besides, thyroid peroxidase antibody or thyroglobulin antibody was positive in 7 cases. The blood glucose of 4 children with pancreatic injury was 25.0 (17.0-33.0) mmol/L, and C-peptide was 0.4 (0.3-0.5) mg/L. Glutamate dehydrogenase antibody, protein tyrosine phosphatase antibody and zinc transporter 8 antibody were positive in two cases. After treatement with immunosuppressant or immunoglobulin combined with glucocorticoid or nonsteroidal antiinflammatory drugs for rheumatic symptoms, and levothyroxine or insulin for endocrine diseases, they were all followed up for more than 6 months and maintained clinical stability.Conclusions:Rheumatic diseases in children can be complicated with endocrine disorders, and the involved organs are usually thyroid and pancreas. In children with rheumatic disease, thyroid injury usually has subtle onset, whereas pancreas injury develops rapidly, even life-threatening. Insulin should be used persistently under the instruction of endocrinologist.

Objective: To improve the understanding and diagnosis and treatment level of infant with Takayasu arteritis (TA) by analyzing the clinical features of 14 pediatric patients and reviewing related articles. Methods: The clinical and follow-up data of infants with TA who were admitted to the Children′s Hospital Affiliated to Capital Institute of Pediatrics between July 2016 and May 2019 were retrospectively analyzed.By reviewing related articles, the clinical features of this disease were summarized. Results: The age of 14 patients (including 6 males and 8 females) were between 1 month and 23 days and 28 months.The most common clinical manifestations were fever in 10 cases (71.4%), hypertension in 9 cases (64.3%), weak or no pulse in 5 cases (35.7%). According to the clinical type of lesion vessels, 11 cases (78.5%) were generalized type, 3 cases (21.4%) were brachiocephalic artery type, and there was no thoracic abdominal aorta or single pulmonary artery type in this group.Among 14 infants with TA, 12 cases had common carotid artery, carotid artery, subclavian artery, coronary artery and its branches (anterior descending branch, circumflex branch) involved (85.7%); 11 cases had renal artery involved (78.6%); 9 cases had radial artery involved (64.2%); 8 cases had abdominal aorta involved (57.1%); 6 cases had descending aorta involved (42.9%); 6 cases had thoracic aorta involved (42.9%); 6 cases had superior mesenteric artery involved (42.9%); 5 cases had femoral artery involved (35.7%); 5 cases had pulmonary artery involved (35.7%); and 4 cases had brachial artery involved (28.6%). In those 14 patients, 11 cases were misdiagnosed, and 3 cases had unclear diagnosis, with misdiagnosis duration of 18 days to 2 months.In misdiagnosed cases, 8 cases were misdiagnosed as atypical Kawasaki disease.Among those 14 cases, the ranges of most lesions were gradually decreased, and the slightly involved vessels even completely returned to normal state after treatment in 7 cases.The vascular imaging showed no significant exacerbation or improvement in 4 cases.Nine cases developed hypertension, the blood pressure of whom could be controlled within normal range with hypotensive drugs which could not be interrupted.Physical examination found weak or no pulse in 5 cases who were not improved.Among 14 patients, 7 cases showed normal development, while the height and body mass of another 7 cases were the 25^th percentile below those of normal children of the same age.All 14 patients were followed up for 2-22 months and received regular treatment without recurrence. Conclusions TA patients aged less than 3 years tend to have more blood vessels involved, be in serious condition and have higher rate of misdiagnosis.The disease can be controlled quickly after treatment, but vascular diseases may be developed easily.Some patients have a poor prognosis.

Objective:To analyze the clinical characteristics of infantile Takayasu arteritis and the efficacy of infliximab (IFX).Methods:Clinical manifestations, laboratory investigations and infliximab intervention of a case with infantile Takayasu arteritis, who was admitted to Department of Rheumatism and Immunology, Children′s Hospital, Capital Institute of Pediatrics in January 2018, were reviewed and analyzed. The related literature published from the beginning to March 2020 were retrieved from CNKI, Wanfang, SinoMed and PubMed with the keywords of"Takayasu arteritis","Infant" in both Chinese and English.Results:This case was a 70-day-old boy admitted due to recurrent fever for 20 days. On admission, his blood pressure were 104/90, 95/59, 125/80, and 152/125 mmHg (1 mmHg=0.133 kPa) in the right arm, left arm, right leg, and left leg, respectively. The complete blood cell count showed leukocytosis (22.6×10 9/L), thrombocytosis (858×10 9/L) and mild anemia (80 g/L). He also had elevated erythrocyte sedimentation rate (119 mm/1h), serum ferritin (598 μg/L) and C-reactive protein (112 mg/L). Computed tomographic angiography (CTA) showed narrowing of the thoracic and abdominal aorta, with thickening and heterogenous enhancement of the vessel wall. Coronary artery ultrasound detected dilatation and wall thickening of the bilateral coronary arteries, and uneven dilatation of the middle segment of the right coronary artery, showing bead-like change. Vessel wall thickening was also found in the other main arteries, including both femoral arteries, axillary arteries, carotid arteries, and subclavian arteries, and both superficial femoral arteries were slightly narrowed in the distal segments. The diagnosis of TA was confirmed, and the boy was treated with infliximab monotherapy (5 mg/(kg·every time), a total of 13 times). Then his body temperature and all inflammatory markers were normalized, and the vascular pathology was resolved according to the radiography. No side effects such as allergy or infection were noted during the treatment. During the 2 years and 6 months of follow-up, the boy maintained normal growth and development. Literature review found 8 related articles, and one of them was in Chinese but had limited information. In the other 7 papers, a total of 7 infants with TA were reported. The most common symptom was fever (5 cases), and inflammatory markers usually elevated, and the most common affected artery was abdominal aorta (6 cases). Most cases were treated with glucocorticoid. Conclusions:TA is a rare disease in infants, usually presents with fever and increased inflammatory markers. At the early stage, infliximab monotherapy could effectively control the symptoms and ensure normal growth and development.

Objective To investigate the effects of glaucocalyxin A ( GLA) on the expression of signal transduction and activator of transcription 3 (STAT3) signaling pathway in HCCLM3 cells for better understand-ing the role of GLA in tumor metastasis. Methods HCCLM3 cells were stimulated by different concentrations (0. 1 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml and 1000 ng/ml) of GLA for 48 h. Expression of IL-6, STAT3/pSTAT3Tyr705 and MMP9 at mRNA and protein levels were detected by qRT-PCR and Western blot, respectively. Transwell invasion and migration assays were performed to analyze cell invasion and migration. ELISA was used to measure the concentrations of IL-6 in culture media. Results Expression of IL-6 at mRNA and protein lev-els, STAT3Tyr705 phosphorylation, and the migration and invasion of HCCLM3 cells were significantly enhanced after stimulation of HCCLM3 cells with 0. 1 ng/ml of GLA, but inhibited by GLA at the concentration of 1000 ng/ml. Moreover, more IL-6 was secreted out of the HCCLM3 cells treated with 0. 1 ng/ml of GLA. Conclu-sions GLA might affect the metastasis of HCCLM3 cells through regulating the expression of IL-6 and the phos-phorylation of STAT3Tyr705. These regulatory effects were closely related to the concentration of GLA.