Objective:To study the mechanism of icariin inhibiting the proliferation of human PCa PC-3 cells based on cell metabolomics technology.Methods:We determined the proliferation activity of human PC-3 cells by methyl thiazolyl tetrazolium(MTT)assay,and compared the proliferation of the PC-3 cells among the control,5-fluorouracil and icariin intervention groups.Using the Bligh Dyer method,we extracted endogenous metabolites from the cells,analyzed the metabolic profile by ultra-high pressure liquid chromatography tandem quadrupole time-of-flight mass spectrometry,identified the differential metabolites by principal component anal-ysis and orthogonal partial least-squares discrimination analysis,and enriched the metabolic pathways based on the MetaboAnalyst data-base.Results:Icariin significantly inhibited the proliferation of human PCa PC-3 cells.A total of 89 differential metabolites were i-dentified,mainly including amino acids,phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine,and lysophosphati-dylethanolamine,all with the tendency to return to the normal level after icariin intervention.Icariin significantly downregulated the metabolic levels of the glycerophospholipid metabolites phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine and ly-sophosphatidylethanolamine,and upregulated those of amino acid metabolites tryptophan,leucine,and proline in the PC-3 cells.Conclusion:Icariin inhibits the proliferation of human PCa PC-3 cells,which may be closely related to its regulatory effect on lipid metabolism(glycerophospholipid metabolism)and amino acid metabolism.

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

Objective: To investigate a SARS-CoV-2 epidemic reported in Rongcheng City, Weihai, Shandong Province. Methods: The SARS-CoV-2 nucleic acid positive patients and their close contacts were investigated, and the whole genome sequencing and genetic evolution analysis of 9 variant viruses were carried out. An infection source investigation and analysis were carried out from two sources of home and abroad, and three aspects of human, material and environment. Results: A total of 15 asymptomatic infections were reported in this epidemic, including 13 cases as employees of workshop of aquatic products processing company, with an infection rate of 21.67% (13/60). Two cases were infected people's neighbors in the same village (conjugal relation). The first six positive persons were processing workers engaged in the first process of removing squid viscera in the workshop of the company. The nucleic acid Ct value of the first time were concentrated between 15 and 29, suggesting that the virus load was high, which was suspected to be caused by one-time homologous exposure. The whole genome sequence of 9 SARS-CoV-2 strains was highly homologous, belonging to VOC/Gamma (Lineage P.1.15). No highly homologous sequences were found from previous native and imported cases in China. It was highly homologous with the six virus sequences sampled from May 5 to 26, 2021 uploaded by Chile. The infection source investigation showed that the company had used the squid raw materials captured in the ocean near Chile and Argentina from May to June 2021 over the last 14 days. Many samples of raw materials, products and their outer packages in the inventory were tested positive for nucleic acid. Conclusion: This epidemic is the first local epidemic caused by the VOC/Gamma of SARS-CoV-2 in China. It is speculated that the VOC/Gamma, which was prevalent in South America from May to June 2021, could be imported into China through frozen squid.
Humans ; SARS-CoV-2 ; COVID-19 ; Epidemics ; China/epidemiology*

Objective: To investigate the clinical features of children with chronic nonbacterial osteomyelitis (CNO), and raise awareness among clinicians. Methods: In this retrospective study, 18 patients with CNO who were diagnosed in Children's Hospital of Fudan University from January 2015 to December 2021 were included. Results: Eighteen children with CNO (12 males, 6 females) were identified. Their age at onset was 9 (5, 11) years, the delay in diagnosis was 2 (1, 6) months, and follow-up-was 17 (8, 34) months. The most common symptoms were fever in 14 children, as well as bone pain and (or) arthralgia in 14 children. In terms of laboratory results, normal white blood cell counts were observed at onset in 17 patients; increased erythrocyte sedimentation rate (ESR) in all patients; increased C reactive protein (CRP) over the normal value in 14 patients. Of the 18 patients, 2 had positive antinuclear antibodies, while none had positive human leukocyte antigen-B27 or rheumatoid factor. Imaging examination revealed that all the patients had symmetrical and multifocal skeletal lesions. The number of structural lesions detected by imaging investigation was 8 (6, 11). The most frequently affected bones were tibia in 18 patients and femur in 17 patients. Bone biopsy was conducted in 14 patients and acute or chronic osteomyelitis manifested with inflammatory cells infiltration were detected. Magnetic resonance imaging (MRI) found bone lesions in all the patients and bone scintigraphy were positive in 13 patients. All the patients were treated with nonsteroidal anti-inflammatory drugs, among whom 10 cases also treated with oral glucocorticoids, 9 cases with traditional disease modifying anti-rheumatic drugs, 8 cases with bisphosphonates and 6 cases with tumor necrosis factor inhibitors. The pediatric chronic nonbacterial osteomyelitis disease activity score, increased by 70% or more in 13 patients within the initial 6-month follow-up. Conclusions: The clinical manifestations of CNO are lack of specificity. The first symptom of CNO is fever, with or without bone pain and (or) arthralgia, with normal peripheral blood leukocytes, elevated CRP and (or) ESR. Whole body bone scanning combined with MRI can early detect osteomyelitis at subclinical sites, and improve the diagnostic rate of CNO.
Female ; Male ; Humans ; Child ; Retrospective Studies ; Osteomyelitis/drug therapy* ; Arthralgia ; Diphosphonates ; Fever ; Graft vs Host Disease

OBJECTIVE To investigate the pharmacological effect of ursolic acid (UA) on colitis-associated colorec?tal cancer (CAC) and its underlying mechanism based on the Wnt signaling pathway. METHODS The CAC model in mice was established by azoxymethane (AOM) combined and dextran sulfate sodium salt (DSS), accompanied by treat?ment with various dosages of UA and concomitant appraisal of body weight, stool and physical state of the mice. After the sacrifice of the mice, the tumor and length of the colorectum were measured, followed by retrieval of the liver, spleen, thymus and tumor tissue for downstream assays. The levels of inflammatory factors interleukin-6 (IL-6), IL-1βand C-reactive protein (CRP) in the tumor and serum were examined by enzyme-linked immunosorbent assay (ELISA). The pathological changes of colorectal tissues were observed by HE staining. The levels in tumors of Wnt/β-catenin sig?naling pathway-related proteins Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry (IHC). The mRNA expressions of Wnt4, GSK-3β,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, Bax, caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR (RT-qPCR). The protein levels of Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, phospho-β-catenin, phospho-GSK-3β, Bcl-2 and Bax in tumors were probed by analyzed by Western blotting (WB). Also, RNA-seq was employed to assess the gut microbiota in the mice. RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC, evidenced by improved physical state, body weight, survival rate, colorectal length, the mass of liver, thy?mus, spleen, and decreased CAC load and colorectal mass. UA attenuated the levels of IL-6, IL-1β and CRP in the mouse serum and colorectal tumor in a dose-dependent manner. HE staining showed that UA lessened carcinogenesis in the colorectum, with lower infiltration of lymphocytes, versus the control. IHC indicated that UA mitigated the expres?sion of Wnt4,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and promoted the GSK-3βexpression, compared with the control. Furthermore, UA diminished the mRNA expressions of Wnt4, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and heightened the mRNA levels of GSK-3β, caspase-3, capase-9 and Bax in CAC. The results of mRNA expressions were verified by WB analysis, which revealed that UA impeded the protein expression of Wnt4,β-catenin, c-Myc, cyclin D1, Bcl-2, TCF4, LEF1, and elevated the protein levels of GSK-3βand Bax, phospho-β-catenin in mouse CAC. In addi?tion, UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC. CONCLU?SION Ursolic acid may protect against CAC, potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.
Adolescent ; Adult ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Pandemics ; Pneumonia, Viral ; drug therapy ; Prospective Studies ; Young Adult

Betacoronavirus ; genetics ; Coronavirus Infections ; diagnosis ; Fluorescence ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Pandemics ; Pneumonia, Viral ; diagnosis ; Polymerase Chain Reaction ; methods

Objective: To analyze the electrophysiological characteristics and the therapeutic efficacy of irrigated-tip catheter radiofrequency ablation(RFA) without radiation for pregnant women with focal atrial tachycardia(AT) originating from the right atrial appendage (RAA). Methods: Data from 55 women with focal AT, who underwent radiofrequency ablation (RFA) in the First Affiliated Hospital of Zhengzhou University from October 2016 to March 2019, were screened. 2 non-pregnant women with right atrial appendage tachycardia (RAAT) and 4 pregnant women with non-RAAT were excluded. The remaining 49 cases were divided into RAAT during pregnancy group (n=6, including 4 cases of tachycardia-induced cardiomyopathy) and non-pregnant and non-RAAT group (control, n=43). Under the guidance of three-dimensional mapping system, the earliest activation site was identified, RFA with the irrigated catheter without x-ray fluoroscopy was performed in RAAT patients during pregnancy, all patients in control group underwent non-zero-ray ablation. Patients were followed up at 3, 6, 12 months post procedure, and yearly follow up thereafter in outpatient clinic. Electrocardiogram or Holter monitoring was performed during follow up. AT recurrence and surgical complications were recorded during follow up. At 6 months after RFA, echocardiography examination and laboratory examination including N-terminal B-type brain natriuretic peptide measurement were performed in the pregnant patients, delivery results were also recorded in the pregnant patients. The electrophysiological characteristics of RAAT during pregnancy were analyzed, the therapeutic efficacy of RFA was compared between the two groups. Results: This study is a retrospective study. Age ((30.7±6.2)years vs. (57.2±11.7)years), left ventricular ejection fraction ((46.0±12.8)% vs. (60.1±5.9)%), proportions of organic heart disease (0% vs. 58%) were significantly lower in the RAAT patients during pregnancy group than in control group (P<0.05), while proportions of patients with persistent tachycardia (100% vs. 7%), symptoms of chest distress and palpitation (6/6 vs. 49%) and left ventricular ejection farction≤50% (4/6 vs. 9%) were significantly higher in RAAT group than in control group (P<0.05), heart rate was similar between the two groups ((163.7±11.1)beats/minutes vs. (153.7±15.2)beats/minutes, P>0.05). The characteristic P-wave morphology was observed in RAAT patients during pregnancy, i.e, P wave was mostly upright (5/6) in inferior-leads (Ⅱ, Ⅲ, aVF) and in lead I and aVL, deep and wide negative P wave was found in V₁ lead (5/6), and gradually became positive from V₂-V₆. The mean tachycardia cycle length was (361.7±38.5) ms. Three-dimensional mapping showed that the origin points of the 6 RAAT pregnant patients were all scattered in the local region, the local region was ablated accordingly, 2 patients (2/6) received extensive ablation of local areas. Immediate successful rate was similar between the two groups (6/6 vs. 93%). During follow up ((15.3±4.0) months), no complications were observed after RFA, postoperative recurrence rate was similar (1/6 vs. 12%). Uncomplicated delivery was reported in all 6 pregnant RAAT post ablation. Normal cardiac structure and function was observed in the 4 pregnant patients with tachycardia-induced cardiomyopathy post ablation. Compared to pre-ablation phase, reduced left atrial dimension ((30.3±1.3) mm vs. (36.8±6.7) mm, P>0.05), increased left ventricular ejection fraction ((64.0±2.9)% vs. (39.8±10.7)%), reduced left ventricular end-diastolic dimension ((44.8±4.0) mm vs. (60.0±2.9) mm) and reduced N-terminal B-type natriuretic peptide value ((136.2±47.5) ng/L vs. (3 408.4±901.3) ng/L) were observed at 6 months post ablation (P<0.05). Conclusion: The electrophysiological characteristics are suggestive for focal AT originating from RAA during pregnancy. Under the guidance of 3-dimension activation mapping, no fluoroscopic RFA with irrigated-tip catheter is a safe and effective strategy for the treatment of focal RAAT during pregnancy.
Atrial Appendage/surgery* ; Female ; Humans ; Pregnancy ; Retrospective Studies ; Stroke Volume ; Tachycardia ; Treatment Outcome ; Ventricular Function, Left

Objective To measure and analyze cardiac ventricular sizes of acute pulmonary embolism patients,and compared with normal group,to investigate the morphological changes of heart in patients with acute pulmonary embolism.Methods 75 patients with acute pulmonary embolism were analyzed retrospectively and were divided into two groups according to the score of embolism index:more than or equal to 50％ (group c,33 cases) and less than 50％ (group b,42cases) and compared with normal group (group a,56 cases) to analyze the changes of cardiac ventricular transversal diameter(LR) and anteroposterior diameter (AP).Results The group c compared with group a and b,the right ventricular LR and AP,and the right atrium LR increased significantly (P＜0.05),the left ventricular LR decreased significantly (P＜0.05).The group b compared with the group a,the right ventricular LR and the right atrium AP increased significantly (P＜0.05),the left atrium LR decreased significantly (P＜0.05).The left atrial AP,group b was larger than that of group a and group c (P＜0.05).The left ventricular AP,there was no significant difference between the three groups.The atrial ratio (RA/LA) and the ventricle ratio (RV/LV)of the three groups were significantly different (P＜0.05).According to the product of two lines of the same heart cavity (RL × AP),compared with group a and b,the left atrium and ventricle of group c decreased (P＜0.05),the right atrium and ventricle enlarged (P＜0.05).Compared with group a,the left ventricular angle of group c decreased significantly (88.97±5.47 vs 97.91±7.66,P＜0.001),there was no significant difference between the group b and c (P＞0.05).After the treatment of acute pulmonary embolism,the right ventricular RL × AP is significantly reduced(4 209.57±844.63 vs 5 090.58±1312.69,P=-0.002),the ventricle ratio (RV/LV) is significantly reduced(0.80±0.13 vs 0.93±-0.19,P=0.003.Conclusions The size and shape of heart cavity varied with different pulmonary embolism index,and we can make preliminary observation and evaluate treatment efficacy by using chest CT scan.

Objective To investigate the expression and clinical significance of late endosomal/lysosomal adaptor,mitogen-activated protein kinase and mammalian target of rapamycin activator 3(LAMTOR3)in bladder carcinoma.Methods Oncomine and Expression Atlas were used to extract the useful mining gene chip database for analyzing the expression of LAMTOR3 in bladder carcinoma tissues and cell lines,and the correlation of LAMTOR3 with the clinicopathological features were analyzed.RT-PCR,Western blot,and immunohistochemistry were performed to detect the expression of LAMTOR3 in bladder carcinoma cell lines,specimens,and adjacent normal tissues for verifying the results exploited from the above databases.Results The Expression Atlas showed that LAMTOR3 had high expressions in Hs172.T,HT-1376,RT4,JMSU-1,and T24 cell lines among 20 bladder carcinoma cell lines,among which the LAMTOR3 expression was different.Oncomine reported that LAMTOR3 expression in bladder carcinoma,including invasive(=2.857,=0.005)and non-invasive carcinoma(=3.105,=0.003),was significantly higher than that in adjacent normal tissues.The expression of LAMTOR3 was positively correlated with pathological grade(<0.05).The expressions of LAMTOR3 mRNA in bladder carcinoma cell lines,including UMUC3(=10.84,=0.0084),J82(=21.75,=0.0021),5637(=45.88,=0.0005),and T24(=87.58,=0.0001)were significantly higher than that in normal bladder cell line SV-HUC-1,while its expression in bladder carcinoma tissues was significantly higher than that in adjacent normal tissues(<0.05),so was its protein level in tissues(<0.05).Immunohistochemistry showed that LAMTOR3 protein was over-expressed in bladder carcinoma tissues;its level in invasive carcinoma tissues was higher than that in no-invasive carcinoma tissues and was related closely with the clinical stages(=9.189,=0.002),pathological grades(=4.746,=0.029),and lymphatic metastasis(=6.210,=0.013)but had no significant correlation to sex(=0.965,=0.326),age(=2.126,=0.145),and distant metastasis(=1.261,=0.261).Conclusion LAMTOR3 is highly expressed in bladder carcinoma cell lines and tissues and plays a key role in the development and progression of bladder carcinoma.
Adaptor Proteins, Signal Transducing ; genetics ; Cell Line, Tumor ; Humans ; Prognosis ; Urinary Bladder Neoplasms ; genetics ; pathology