Aim To observe the inhibitory effect of dihydroartemisinin combined with COX-2 inhibitor on S180 sarcoma and their possible antitumor mechanisms.Methods The ICR mice model of the subcutaneous transplanting tumor was established by S180 sarcoma to investigate the treatment effect of dihydroartemisinin and COX-2 inhibitor.Expressions of VEGF,COX-2 and CD31 in S180 sarcoma were detected and the amount of leukocyte was also observed.Results Dihydroartemisinin combined with COX-2 inhibitor could potently inhibit tumor growth and inflammation.The maximal antitumor rate reached 55.38%.The results of immunohistochemistry showed that COX-2 and VEGF protein expressions were weakened by dihydroartemisinin and COX-2 inhibitor,versus the control groups.Further,RT-PCR analysis showed that the expression of VEGF mRNA was also effectively decreased.Finally,a significant down-regulation effect of COX-2 and VEGF protein expression was observed.Conclusions Dihydroartemisinin combined with COX-2 inhibitor can significantly inhibit S180 tumor.The antitumor mechanism of these two drugs might be closely related to the effect of COX-2 and VEGF expression suppression.

Abstract To further standardize the procurement management of reagents and consumables in disease control and prevention institutions in Zhejiang Province and facilitate incorruptible health building, the procurement management for reagents and consumables in Zhejiang disease control and prevention institutions was created by Zhejiang Provincial Center for Disease Control and Prevention in 2019. Based on three-layer architecture of SaaS, PaaS and IaaS, this platform, which is easy to perform, safe and practical, provides modular portal website services, and its main functions include procurement budget management, procurement plan management, order management, bidding management, contract management, execution-of-contract and acceptance, and payment management. This platform, which was initiated to be run on early 2020, was found to be improve the procurement efficiency, safe management costs, reduce the internal control risk, and facilitate the containment of COVID-19, which may provide the support to improving procurement management and laboratory capability in disease control and prevention institutions.

Objective To analyze the changes in peripheral blood monocyte subpopulations in patients with primary, secondary and latent syphilis. Methods Flow cytometry was used to detect CD14highCD16- and CD14+CD16+ monocyte subpopulations in peripheral blood from 58 patients with untreated syphilis, including 36 cases of latent syphilis,8 cases of primary syphilis and 14 cases of secondary syphilis, as well as from 65 normal human controls. Restflts Compared with the normal controls, the proportion of CD14+CD16+ monocytes among total monocytes was significantly elevated (12.0% ± 5.0% vs 6.0% ± 3.3%, t = 7.25, P < 0.01), while that of CD14highCD16- monocytes was down-regulated (88.0% ± 5.1% vs 94.0% ± 3.5%, t = -7.20, P < 0.01). No statistical difference was observed in the proportion of CD14+CD16+ or CD14hhighCD16- monocytes among the patients with primary syphilis, secondary syphilis and those with latent syphilis (all P > 0.05). Conclusions The changes in peripheral blood monocyte subpopulation in patients with untreated syphilis may be associated with the permanent infection of Treponema pallidum, but have no obvious correlation with clinical stage of syphilis.

Objective To comprehensively study the oxidative stress of bone tissue in rats with chronic fluorosis treated with anti-oxidant,the oxidative damage of lipid,protein and DNA.Methods Forty Wistar rats weaned 2 weeks were randomized by weight and divided into 4 groups according to body weight,control group (treated with tap water) and 3 NaF (sodium fluoride) exposure groups (treated with NaF at 50,150 and 250 mg/L),5 female rats and 5 male rats in each group.NaF was given through drinking water.After 6 months of treatment,a 12-hour urine samples were collected,then rats were killed,serum was collected,right rear tibiofibula was separated.Bone and urinary fluoride content and incidence rate of dental fluorine were studied and the levels of bone tissue suppression function of hydroxy free radical,superoxide dismutase (SOD),catalase (CAT),glutathione peroxidase (GSH-Px),8-hydroxydeoxyguanosine (8-OHdG),protein carbonyls (PCO),and malonaldehyde (MDA) were assayed.Results ① Results of suppression function of hydroxy free radical:The difference of bone tissue suppression function of hydroxy free radical among control [(22.99 ± 4.31)U/mg prot],low-excess dose [(22.76 ± 8.11)U/mg prot],medium-excess dose [(13.47 ± 4.56)U/mg prot] and high-excess dose [(19.40 ± 5.92)U/mg prot] groups was statistically significant (F =5.01,P ＜0.05).②Results of SOD:The difference of bone tissue SOD among control [(5.06 ± 1.16)U/mg prot],low-excess dose [(5.32 ± 1.18)U/mg prot],medium-excess dose [(3.71 ± 0.72)U/mg prot] and high-excess dose [(4.80 ± 1.10)U/mg prot] groups was statistically significant (F =4.44,P ＜0.05).③ Results of CAT:The difference of bone tissue CAT among control [(25.20 ± 5.91)U/mg prot],low-excess dose [(22.53 ± 7.10) U/mg prot],medium-excess dose [(17.96 ± 4.71)U/mg prot] and high-excess dose [(19.52 ± 5.52)U/ mg prot] groups was statistically significant (F =2.85,P ＜0.05).④Results of GSH-Px:The differences of bone tissue GSH-Px among control [(52.86 ± 12.88)U/mg prot],low-excess dose [(70.05 ± 15.72)U/mg prot],medium-excess dose [(51.55 ± 6.97)U/mg prot] and high-excess dose [(57.47 ± 10.99) U/mg prot] groups was statistically significant (F =4.89,P ＜0.05).⑤Results of PCO:The differences of bone tissue PCO among control [(58.73 ± 20.86)ng/L],low-excess dose [(89.41 ± 26.20)ng/L],medium-excess dose [(97.07 ± 22.24)ng/L] and highexcess dose [(83.96 ± 29.55)ng/L] groups was statistically significant (F =4.43,P ＜0.05).⑥Results of 8-OHdG:The differences of bone tissue 8-OHdG among control [(87.66 ± 6.32)ng/L],low-excess dose [(86.31± 6.30)ng/L],medium-excess dose [(92.17 ± 4.28)ng/L] and high-excess dose [(88.02 ± 6.14)ng/L] groups was not statistically significant (F =1.88,P ＞ 0.05).⑦Results of MDA:The differences of bone tissue MDA among control [(3.70 ± 1.73) nmol/mg prot],low-excess dose [(2.10 ± 0.95)nmol/mg prot],medium-excess dose [(3.32± 2.20)nmol/mg prot] and high-excess dose [(2.71 ± 2.18)nmol/mg prot] groups was not statistically significant (F =1.37,P ＞ 0.05).Conclusions The activity of SOD and CAT of bone tissue are inhibited and suppression function of hydroxy free radical is decreasing under fluorosis influence,which results in protein damage.Oxidative stress is considered to be one of the mechanisms of skeletal fluorosis.

Objective To analyze the important abnormal results of physical examination of the staff in our hospital in recent 2 years,and to provide evidence for the health management of the staff in our hospital.Methods The physical examina-tion data of hospital staff in recent 2 years were retrospectively analyzed,and the important abnormal results were statistically ana-lyzed.Results A total of 3 584 employees participated in physical examination,including753 males and 2831 females.There were 92 cases with significant abnormal results,and the total detection rate was 2.57%.The detection rate of significant abnor-mal results was slightly lower in males(17cases,2.26%)than in females(75cases,2.65%),and the age of females[(48.89±19.53)years]was lower than that of males[(55.68±17.43)years].The age group with the most significant detec-tion rate of important abnormal results was 50-59 years old(3.07%),and the diseases detected by important abnormal results were as follows:There were 26 thyroid tumors,19 lung tumors,13 breast tumors,12 space occupying cases(3 liver,4 kidney,2 adrenal glands,1 adnexa,1 pancreas,1 mediastinum),9 vascular lesions,6 abnormal tumor markers,5 cervical lesions,1 tuberculosis,and 1 subdural hematoma.Among them,thyroid tumors,breast tumors,lung tumors and cervical lesions were the main cases in women,and vascular diseases,lung tumors,space-occupying lesions(liver and kidney)and thyroid tumors were the main cases in men.Conclusion Physical examination is of great significance in detecting important abnormal diseases.We should attach great importance to physical examination,detect serious diseases as early as possible,and strengthen health man-agement accordingly.

The interaction between oncolytic virus (OV) and the tumor microenvironment or body immune system is critical to the outcome of antitumor therapy. The antitumor mechanism of OV is complex, which involves direct cytotoxic effects, immunogenicity change in tumor microenvironment, the role of tumor vasculature, and activating of the antitumor immunity response, to reach the goal of killing the tumor cells infected or uninfected, and confirming the continous favorable effects.

Objective:To explore the interventional effect of β-sitosterol on ovalbumin(OVA)-induced allergic asthma rats and its potential mechanism.Methods:SD male rats were randomly divided into normal group(CON),model group(M),positive drug dexamethasone group(DEX,0.075 mg/kg)and β-sitosterol group(Sit,50 mg/kg).A rat model of allergic asthma was estab-lished by intraperitoneal injection of OVA with aluminum hydrogen solution,and nebulized inhalation of OVA to stimulate.Rats were given intragastric administration 30 min before aerosol challenge,and after continuous administration for 7 days,the indicators of cough and asthma and tracheal phenol red excretion were detected.HE staining was used to observe pathological changes of lung tis-sue.Flow cytometry was used to detect reactive oxygen species(ROS)generation,apoptosis level and ratios of Th17 and Treg cells in peripheral blood.Biochemical method was used to detect contents of MDA,and activities of T-SOD and GSH-Px in rat lung tissues.ELISA was used to detect levels of Th17 and Treg-related cytokines(TNF-α,IL-4,IL-6,IL-17A,and IL-35).Results:Compared with model group,β-sitosterol significantly prolonged the incubation period of cough and gasp in rats with allergic asthma,reduced the frequency of cough and gasping,and promoted the excretion of phenol red in trachea;significantly reduced inflammatory infiltration in lung tissue of asthmatic rats;observably reduced MDA content in lung tissue,ROS of primary lung cell and apoptosis levels of asthmatic rats,increased the activities of T-SOD and GSH-Px;markedly reduced proportion of Th17 cells and levels of pro-inflammatory cyto-kines TNF-α,IL-4,IL-6 and IL-17A,increased proportion of Treg cells and levels of anti-inflammatory cytokine IL-35.Conclusion:β-sitosterol can ameliorate airway inflammation and oxidative damage in OVA-induced allergic asthmatic rats,and its mecha-nism may be related to the regulation of β-sitosterol on Th17/Treg immune imbalance and oxidative stress response.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.
Rats ; Animals ; Doxorubicin/adverse effects* ; Nephrotic Syndrome ; AMP-Activated Protein Kinases/metabolism* ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis