Objective To explore the protective role of lipoxin A4 (LXA4) during early process of atherosclerosis formation in rats with juvenile metabolic syndrome (MS).Methods Rat models of juvenile MS were established with 3-week Sprague-Dawley (SD) rats fed on high-carbonhydrates and high-fat diet for 6 weeks.The other qualified ones were randomly grouped into model group,LXA4 low-dose group,LXA4 middle-dose group,and LXA4high dose group,and a control group fed with normal forage.The low,middle,high-dose groups were injected different doses of LXA4 daily,while the model group and control group were injected with the same dose of isotonic NaCl solution for 2 consecutive weeks.After 2-week medication,the visceral adipose tissue were isolated by laparotomy and heart blood collected by thoracotomy under anesthesia,followed the fixation of thoracic and abdominal aortas in the immobilized rats.The mRNA expression level of inflammation cytokines interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),C-reactive protein (CRP) in the adipose tissue were determined by semi-quantitative reverse transcription PCR (RT-PCR),respectively.Secretions of IL-6,and TNF-α in serum were determined by enzyme linked immunosorbent assay (ELISA).Immunocytochemistry was used to label endomembrane and middle-membrane of thoracic aorta,and endothelial cell layer in each group and the ratios of thickness of endomembrane and middle-membrane were compared.Results Compared with the control group,weight,body length and abdominal circumference of juvenile MS rats increased significantly (all P ＜ 0.05),and levels of fasting plasma glucose (FPG),triglyceride (TG),high density lipoprotein cholesterol (HDL-C) and insulin in models increased significantly (P ＜ 0.05).RT-PCR showed that the mRNA expressions of inflammatory cytokines IL-6,TNF-α and CRP in adipose tissue in model rats were upexpressed (all P ＜ 0.05).Compared with model rats,mRNA of IL-6,TNF-oα,and CRP in mid,high-dose rats were downexpressed (all P ＜ 0.05),mRNA of TNF-α in low-dose rat downexpressed (all P ＜ 0.05),and there were no significant differences between mRNA expressions of IL-6,CRP in low-dose and model rats according to statistics (all P ＞0.05).Compared with control group,inflammatory cytokines IL-6,TNF-α secreted in serum of model rats were increased significantly (all P ＜ 0.05),and inflammatory cytokines secreted in serum of intervention rats were decreased significantly compared with model rats (P ＜ 0.05).Pathological changes were as follows:HE staining:compared to model group,aortic tunica intima of model rats were remarkably thickened and endothelial cell layer was fragmented and incomplete,which was attenuated in each intervention group.The ratios of endomembrane and middle-membrane in rats:at the end of consecutive medication for 2 weeks,the ratios of endomembrane and middle-membrane in model rats were significantly greater than those of control group (P ＜ O.05),and the ratios of endomembrane and middle-membrane in high-dose intervention rats were significantly smaller than those of the model group (P ＜ 0.05),but still greater than control group,while there were no statistical differences between the ratios in low,middle-dose intervention rats and model rats (P ＞ 0.05).Conclusions The increasing inflammatory cytokines are involved in early process of atherosclerosis formation in rats with juvenile MS.LXA4 by reducing the expression of inflammatory factor level in adipose tissue,thereby reducing the inflammatory cytokines in serum,alleviate the damage of arterial wall.

Objective To investigate the imaging characteristics of lymphoscintigraphy in postoperative breast cancer patients and evaluate its diagnostic value in breast cancer-related lymphedema (BCRL).Methods Seventy-nine breast cancer patients who underwent mastectomy and axillary lymph node dissection were studied. Patients ( n = 158 ) were divided into the study ( affected arms, n = 79 ) and control groups ( contralateral arms, n = 79). After subcutaneous injection of 99Tcm-dextran via the first interphalangeal space, lymphoscintigraphy was performed at 10 min, 1,3, 6 h respectively. Sensitivity and specificity of lymphoscintigraphy for detection of BCRL were calculated. Results There were significant differences in the amount of visualized lymph nodes, lymphatic integrity and backflow pattern between the two groups.Lymphatic drainage was preserved in 96.2% (76/79) of the contralateral arms and only 5.1% (4/79) of affected arms. 87.3% (69/79) and 74.7% (59/79) of control arms had ≥2 lymph nodes in axilla and supraclavicular regions, respectively; while none ( 0/79 ) and 5.1% (4/79) of the affected arms had ≥ 2lymph nodes in both regions, respectively. Four backflow patterns of radiotracer in subcutis were observed in the affected arms: normal (2.5% , 2/79), dilatated (55.7%, 44/79), diffused (36.7%, 29/79) and without backflow (5.1%, 4/79 ). The sensitivity and specificity of "lymphatic integrity" and "backflow pattern" on lymphoscintigraphy for detecting BCRL were 97.5% (77/79) and 96.2% (76/79), 94.8%(73/77) and 100.0% (81/81), respectively. Conclusion Lymphoscintigraphy is a noninvasive, accurate and effective imaging modality for the evaluation of BCRL.

Objective To evaluate the lymphoscintigraphic imaging characteristics for the patients with lower limb lymphedema and to establish a novel grading system for the injury to lower limb lymphatic system. Methods One hundred and sixty six consecutive patients (332 lower limbs) with lower limb lymphedema after surgical and(or) radiotherapy treatment for gynecological cancer were recruited into this retrospective study. The lymphoscintigraphy studies were performed after subcutaneous injection of 111～185 MBq (0. 1～0. 15 ml) of 99Tcm-DX into the webbed space between the first and second toes of both feet. Based on the integrity of lymphatic vessel and the extension of dermal diffusion on lymphoscintigram,the lymphatic injury to the lower limb was graded as 0, 1,2 and 3 respectively. The lymphedema of the limb was staged as 0, Ⅰ , Ⅱ a, Ⅱ b, Ⅲ by the standard of Consensus Document of the International Society of Lymphology (ISL). Chi square test was carried out to validate the established grading system for the assessment of the injury to the lower limb lymphatic system. Results The lymphoscintigraphic imaging characteristics included lymphatic blockage, dermal backflow, no visualization of lymphatic or lymph node, lymphocele and lymph fistula in the lower limb, pelvis and abdomen. There were 65 (19.6%), 71 (21.4%),131 (39.5%), 62 (18.7%) and 3 (0.9%) limbs staged as 0, Ⅰ , Ⅱa, Ⅱb, and Ⅲ for lymphedema while 36(10.8%), 79(23.8%), 116(34.9%) and 101 (30.4%) limbs graded as 0, 1, 2, and 3 for lymphatic injury. There was a statistically significant correlation between the grading methods (χ2 =313.483, P <0.001). The patients who underwent radiotherapy had a higher incidence rate of grade 2 and 3 (70.5%, 158/224) than those who underwent surgery (53.6%, 59/108) (χ2 = 9.662, P = 0.022).The patients with erysipelas had a higher incidence rate of grade 3(73.1%, 38/52) than those without erysipelas (43.9%, 50/114) (χ2= 12.238, P<0.001). The incidence rate of grade 3 increased with the duration of lymphedema after treatment: 36.6% (34/93) for less than 1.5 years, 72.3% (34/47) for between 1.5 to 5 years, and 76.9% (20/26) for more than 5 years (χ2 = 23.123, P<0.001). The grade of lymphatic injury showed no significant difference among 3 types of gynecological cancers (χ2 = 4.000, P =0.676), or between the patients with and without chemotherapy (χ2 =0.411, P=0.938). Conclusions Lymphoscintigraphy is a reliable modality to diagnose lower limb lymphedema after treatment for gynecological cancer. The injury grading system could provide objective assessment of the lymphatic damage.

Objective:To analyze the molecular characteristics of Echovirus 11 (Echo11) strains isolated in Xiangyang, Hubei Province from 2016 to 2017 based on the sequences of VP1 gene.Methods:Rectal and throat swab specimens were collected from children with hand, foot and mouth disease (HFMD) in Xiangyang from 2016 to 2017. Echo11 strains were detected by real-time reverse transcriptase PCR (RT-PCR) and isolated after cultured in human rhabdosarcoma (RD) cells. The VP1 regions of Echo11 strains isolated from RD cells and the whole genomes of three representative Echo11 strains were amplified by conventional RT-PCR and the sequences were analyzed. DNAStar7.0 (MegAlign) and MEGA6.0 (Data) were used to analyze the homology and mutation sites in nucleotide and amino acid sequences. Neighbor-joining method was used to construct phylogenetic trees. Recombination analysis was performed with SimPlot software (BootScanning).Results:A total of 11 Echo11 strains were isolated from 3 494 HFMD cases, accounting for 0.31%. They were highly homologous in the VP1 gene. These strains shared 98.4%-100.0% homology in nucleotide sequences and 98.3%-100.0% homology in amino acid sequences. The homology between the 11 Echo11 strains and the prototype strain (Echo11/Gregory, X80059) was 73.9%-74.8% in nucleotide sequences and 87.7%-88.7% in amino acid sequences. All of the Echo11 strains circulating in Xiangyang were classified into lineage D, having a similarity to the strains circulating in some regions of mainland China since 2013. In multiple regions of the genome, the Echo11 strains isolated in Xiangyang were highly similar to the Henan Echo1 strains in 2010 and the Hubei Echo6 strains in 2015, suggesting there was recombination within the genome of Echo11 strains in Xiangyang.Conclusions:The Echo11 strains circulating in Xiangyang from 2016 to 2017 belonged to lineage D and were recombinant strains.

OBJECTIVETo study the clinical features of hyperparathyroidism due to parathyroid tumors, and evaluate the efficiency of surgical management.

METHODSTwenty-two patients with hyperparathyroidism resulted from parathyroid tumors were reviewed. The age ranged from 32 to 79 years, 9 males and 13 females. Recurrent laryngeal nerve was routinely exposed, and procedures were performed in normal tissue in initial surgery. Additional selective neck dissection of levels II, III, IV, and VI was taken in the cases with recurrent cancer. Local flaps were used to repair the esophageal defects after resecting tumors. The recurrent laryngeal nerves of 4 cases had to be sacrificed because they were embedded in the tumor tissues despite the nerves had normal function before operation. Prophylactic tracheostomy was performed in 5 cases.

RESULTSEight cases were identified pathologically as parathyroid carcinoma, of them four with neck metastasis, and 14 cases as parathyroid adenoma after surgery. Their PTH dropped to normal level within two hours after surgery and hypercalcemia disappeared in two days postoperatively. The PTH and serum calcium were in normal range during the follow-up of 12 to 40 months. Recurrence occurred again in two cases in 6 and 8 months after the removal of the recurrent tumor tissues respectively. Esophageal fistula, chylous fistula and dehiscence of sternotomy developed in three cases separately. The tracheostomy was removed in four cases two weeks after operation and in one case six weeks after operation. One patient with parathyroid adenoma died of hypocalcemia about two weeks after operation and another one with recurrent parathyroid carcinoma also died of hypercalcemia 52 months after revised surgery.

CONCLUSIONExtended resection of tumor and intraoperative PTH assay were strongly suggested for the managements of both benign and malignant parathyroid tumors.

Adult ; Aged ; Calcium ; blood ; Female ; Humans ; Hyperparathyroidism ; etiology ; surgery ; Male ; Middle Aged ; Neck Dissection ; Neoplasm Recurrence, Local ; Parathyroid Hormone ; blood ; Parathyroid Neoplasms ; complications ; surgery ; Retrospective Studies ; Tracheostomy

Objective:To explore the changes of T follicular regulatory (T FR) cells/T follicular helper (T FH) cells and their related cytokines in peripheral blood of children with dust mite allergic asthma, and their clinical significance. Methods:A total of 25 children with acute dust mite allergic asthma (the asthma group) in Affiliated Hospital of Jiangnan University from January to December 2021 and 16 age- and sex-matched healthy volunteers (the healthy control group) at the same time were enrolled in the retrospective study.The percentages of peripheral T FR cells and T FH cells of the 2 groups were measured by flow cytometry.The plasma levels of cytokines[interleukin (IL)-10, IL-21] of the 2 groups were assessed by the flow cytometric microsphere-based array technology.The specific IgE (sIgE) levels of dust mites in 2 groups were detected by fluorescence enzyme immunoassay.The percentage of eosinophils in peripheral blood detected by blood cell analyzer.Data between groups were compared by t-test, and the correlation among indicators was analyzed by Spearman rank correlation analysis. Results:The asthma group had evident T FR cells/T FH cells immune imbalance.Compared with the healthy control group, the asthma group had a significantly lower T FR cells level[(0.11±0.03)% vs.(0.13±0.03)%], a significantly higher T FH cells level[(5.07±1.75)% vs.(3.80 ± 1.60)%], and a significantly lower ratio of T FR cells /T FH cells(0.02±0.01 vs.0.05±0.03) ( t=2.29, 2.30, 3.71; all P<0.05). Compared with the healthy control group, the asthma group had a significantly higher IL-21 level[(547.85±195.13) ng/L vs.(404.94±110.41) ng/L], and a significantly lower IL-10 level[(10.18±3.49) ng/L vs.(14.79±5.65) ng/L] ( t=2.60, 3.15; all P<0.05). The ratio of T FR cells/T FH cells in asthma group was negatively correlated with sIgE ( r=-0.444 2, P=0.026 1), but not related to the eosinophil percentage ( r=-0.135 2, P=0.519 3). Conclusions:Children with dust mite allergic asthma suffer from T FR cells/T FH cells subset imbalance.The imbalanced T FR cells, T FH cells and their related cytokines IL-10 and IL-21 may play a role in regulating the production of asthma sIgE.

BACKGROUNDThree randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). However, data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown. This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy.

METHODSIn the single-arm, open-label, Avastin Therapy for Advanced Breast Cancer (ATHENA) study (NCT00448591), patients with HER2-negative LR/mBC received first-line bevacizumab (investigator's choice of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) combined with taxane-based therapy. The primary endpoint was safety profile and the secondary is time to progression (TTP). A subpopulation analysis was conducted to assess safety and efficacy in Chinese patients.

RESULTSOf 2264 patients treated in ATHENA, 202 were enrolled in China. Bevacizumab was combined with docetaxel in 90% of Chinese patients and paclitaxel in 10%. The most common grade 3/4 adverse events were diarrhoea (in 5.0% of patients) and hypertension (in 2.5% of patients). Grade 3/4 proteinuria occurred in 0.5%. After median follow-up of 17.6 months and events in 56% of patients, median TTP was 9.0 months (95%CI, 8.4-11.1). Overall survival data were immature.

CONCLUSIONSWe found no evidence of increased bevacizumab-related toxicity or reduced efficacy in Chinese LR/mBC patients receiving first-line bevacizumab-taxane therapy compared with predominantly Western populations. The safety profile was generally similar to previously reported LR/mBC trials. Subtle differences may be attributable to different lifestyle and cardiovascular risk factors in Chinese patients compared with the overall population. It appears reasonable to extrapolate findings from bevacizumab-based randomised trials to Chinese populations.

Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Bevacizumab ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; Bridged-Ring Compounds ; adverse effects ; therapeutic use ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2 ; genetics ; metabolism ; Taxoids ; adverse effects ; therapeutic use ; Young Adult

Aim To clarify the regulatory effect of Artesunate(ART) on tumor cell function and cell cycle in the pathological process of esophageal squamous cell carcinoma(ESCC). Methods KYSE450 and TE14 cells were treated with different concentrations of ART. The cells treated with 0 mg •L

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

IF1 (ATPIF1) is a nuclear DNA-encoded mitochondrial protein whose activity is inhibition of the F