AIMTo study the synthesis and anti alpha-adrenoceptor activity of 1,2-dihydro-quinoline-2-one compounds.

METHODSAcylation, bromination and cyclization, and substitute reactions were used in the synthesis of the title compounds IV. A proposed mechanism was showed to explain the unusual compounds 5 and 6 in the route C. The inhibition activity of the six target compounds were tested.

RESULTSTwelve new compounds were synthesized (II1-6 and IV1-6). Among them, six new compounds (IV1-6) are the title compounds. Structure of the title compounds were determined by IR, 1HNMR, MS and HRMS.

CONCLUSIONCompounds IV3, IV4 and IV6 showed inhibitiion activity, and were worth further studying.

Adrenergic alpha-Antagonists ; chemical synthesis ; pharmacology ; Animals ; Aorta ; drug effects ; In Vitro Techniques ; Molecular Structure ; Phenethylamines ; chemical synthesis ; pharmacology ; Quinolones ; chemical synthesis ; pharmacology ; Rabbits ; Receptors, Adrenergic, alpha ; drug effects ; metabolism ; Technology, Pharmaceutical

Objective To explore the relationship between apoptosis promoting effector molecules caspase-3,caspase-9 and lubar intcrvertebral disc protrusion.Methods 99 of operation patients with lubar intervertebral disc protrusion in their mater nity ward were recruited.Among them,single segment of lubar intervertehral disc protrusion were 70 (Group A),more than one segments of lubar intervertebral disc protrusion were 29(Group B).In addition,40 unrelated healthy people from physi cal examination center were enrolled as controls.Enzyme linked immunosorbent assay (ELISA) was used to examine serum caspase-3 and caspase-9 levels in lubar intervertebral disc protrusion patients.Results The level of caspase-3 in control group,group A and group B,respectively were 11.24±0.41,14.31±0.67 and 17.43±1.86 pmol/L.The caspase-3 activity in each group was statistically significant difference (F=8.47,P＜0.01).The level of caspase-9 in control group,group A and group B respectively were 18.54±2.19,30.57±3.63 and 43.68±5.15 pmol/L.The caspase-9 activity in each group was statistically significant difference (F=7.85,P=0.001).Compared with control group,the caspasc 3 and caspase-9 ac tivity in group A (q=3.08.3.29,all P＜0.05),group B (q=5.78,4.50,all P=0.014) was statistically significant differ ence.The caspase-3 and caspase-9 activity in group A,group B was statistically significant difference (q=3.21,3.22,all P＜0.05).Conclusion The augment of caspase-3 and caspase-9 promoted apoptosis of lubar intervertebral disc protrusion.It was connected with quantity of protrusive segments.The more segments of protrusion,the higher caspase-3 and caspase-9 levels of examination would be.

OBJECTIVE：To investigate the research status and hotspots of inhalation therapy for respiratory diseases in the world，and to provide reference for further development of the filed in China. METHODS ：All literatures about inhalation therapy for respiratory disease were retrieved from Web of Science database from the inception to Jan. 1st，2020. The retrieval result analysis function of Web of Science combined with visual analysis function of CiteSpace 5.1.R6SE software were used to analyze included literatures from respective of annual number of articles published ，countries，institutions，categories and co-cited authors ， so as to analyze the research situation in this field. The knowledge map of key words was drawn ，then cluster analysis and burst detection were carried out ，and the research hotspot and development process were analyzed. RESULTS ：A total of 1 385 literatures were included. From 1947 to 2020，the overall trend of annual number of articles published was on the rise. There were 66 countries involved in relevant research ，the United States was in the leading position （the number of articles published accounting for 33.79％ of total articles published ），followed by Germany and UK （the number of articles published accounting for 10.32％， 8.88％ of total articles published ），while Chinese number of articles published accounting for only 3.75％ of total articles published. Institutions involved in this research field included the respiratory diseases research institution ，comprehensive universities and national institute for occupational safety health ；top ranked institutions were Sydney University ，North Carolina University， Harvard University ， etc. The subject category involved molecular biology ， internal medicine ， pharmacology， engineering and other fields. A total of 749 authors were co-cited ，and the co-cited frequency of top two authors were 109，84 times respectively. Through the cluster analysis ，6 major researches hotspots were obtained in this field ，including the dosage form and technology design of inhaled drugs ，the mechanism of inhaled drugs ，the application of inhalation therapy for the obstructive diseases of respiratory system ，the application of inhalation therapy for the infectious diseases of respiratory system ，the application of inhalation therapy for the special population of respiratory diseases，and the risk factors in the application of inhalation （No.2017YFC0909900） therapy for respiratory diseases. Through the sudden detection ， it was found that in the early 1990s，the research in this field was very active ，and there were many research hotspots ；in the early 21st century ， there were several new research hotspots for a short time ，such as metered-dose inhaler ，aerosol，etc.；till the 2020s，there were many research hotspots ，such as nanoparticles，human trials ，etc. CONCLUSIONS ：Researches about inhalation therapy for the respiratory diseases are steadily increasing internationally ，while the researches in this field in China is still very limited. In the future ，our country can pay attention to the international research hotspot and direction in this field ，and further strengthen the exchanges and cooperation with other countries.

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning on the expressions of tyrosine kinase Lyn and spleen tyrosine kinase (Syk) in mast cells of subcutaneous loose connective tissue in the rats with urticaria and explore the potential biological mechanism of EA in the intervention of urticaria. METHODS: A total of 32 SD rats were randomized into a blank group, a model group, an EA group and a positive medication group, 8 rats in each one. Except of the blank group, the passive cutaneous anaphylaxis (PCA) was adopted to prepare the model of urticaria in the rats of the rest three groups. In the EA group, EA was applied to bilateral "Quchi" (LI 11), "Xuehai" (SP 10) and "Zusanli" (ST 36), with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity, once daily, for 20 min each time, consecutively for 7 days. In the positive medication group, loratadine (1 mg•kg•d) was for intragastric administration, once daily, consecutively for 7 days. The samples were collected for index detection 30 min after PCA antigen challenge in the rats of each group. Spectrophotometer was adopted to determine the effusion quantity of Evans blue in the allergized site of skin. HE staining was used to observe the morphological changes in the allergized site of skin. Toluidine blue staining was provided to observe mast cell degranulation in subcutaneous loose connective tissue in the allergized site of skin. Immunohistochemistry was applied to determine the protein expressions of Lyn and Syk during degranulation of mast cells. RESULTS: In the rats of the odel group, the eipdermis of allergized site was thickening, cells were disorganized in hierarchy and inflammatory cells were infiltrated largely in the dermis. In the positive medication group and the EA group, the epidermis was getting thin, cell arrangement was clear and the inflammatory cell infiltration was obviously alleviated as compared with the model group. Compared with the blank group, the OD value of skin dye effusion quantity, the degranulation rate of mast cells and the positive expressions of Lyn and Syk were all increased in the model group (<0.01). Compared with the model group, the OD value of skin dye effusion quantity, the degranulation rate of mast cells and the positive expressions of Lyn and Syk were all reduced in the EA group and the positive medication group (<0.01). Compared with the positive medication group, the degranulation rate of mast cells was increased significantly in the EA group (<0.01). CONCLUSION Electroacupuncture at "Quchi" (LI 11), "Xuehai" (SP 10) and "Zusanli" (ST 36) reduces vascular permeability and gives play to the role of anti-allergy by the way of regulating and controlling the degranulation of mast cells in the rats with urticaria and the effect mechanism of electroacupuncture may be related to the inhibition of protein expressions of Lyn and Syk in mast cells.
Acupuncture Points ; Animals ; Connective Tissue ; metabolism ; Electroacupuncture ; Mast Cells ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Syk Kinase ; metabolism ; Urticaria ; therapy ; src-Family Kinases ; metabolism

Objective: To evaluate the relationship between red blood cell folate (RBC folate) and the prognosis of low-grade cervical intraepithelial neoplasia (CIN 1). Methods: In the married women cohort established in 2014, 564 women with CIN 1 diagnosed by pathology were recruited. The demographic characteristics and factors of cervical intraepithelial neoplasia were collected. Meanwhile, the infection status of human papillomavirus (HPV) was detected by molecular diversion hybridization, and the level of RBC folate was measured by chemical photoimmunoassay. After 24 months of follow-up, pathological examination was performed again to observe the prognosis of participants. The women with reversal were taken as the control group,and those with continuous and progressive CIN 1 were taken as the case group respectively. The relationship between RBC folate and CIN 1 outcome was evaluated by logistic regression model. Results: 453 women completed the follow-up, aged (49.72±6.84) years old. CIN 1 was reversed in 342 women, continued in 58 cases and progressed in 53 cases. The RBC folate level M (Q_1,Q₃) were 399.01 (307.10, 538.97) ng/ml, 316.98 (184.74, 428.49) ng/ml and 247.14 (170.54, 348.97) ng/ml, respectively. With the decrease of RBC folate, the risk of continuous and progressive CIN 1 increased (all P<0.001), while the risk of reversal CIN 1 decreased gradually (P<0.001). Combined with high-risk human papillomavirus (HR-HPV) infection status, low level of RBC folate could increase the risk of CIN 1 progression regardless of HR-HPV infection (HR-HPV infection: OR=21.34, 95%CI: 3.98-114.54; HR-HPV uninfection: OR=11.15, 95%CI: 2.34-53.13). Conclusion: Low level of RBC folate could increase the risk of CIN 1 persistence and progression regardless of HR-HPV infection.
Adult ; Alphapapillomavirus ; Case-Control Studies ; Cervical Intraepithelial Neoplasia ; Erythrocytes ; Female ; Folic Acid ; Humans ; Male ; Middle Aged ; Papillomaviridae ; Papillomavirus Infections ; Uterine Cervical Neoplasms

Objective: To investigate the correlation between methylation in human papillomavirus 16 (HPV16) long control region (LCR) and cervical intraepithelial neoplasia grade ≥2 (CIN2+). Methods: The literature retrieval was conducted by using the databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang data and Weipu according to the inclusion and exclusion criteria, and the retrieval period was from the establishment of the databases to February 27^th, 2022. Software RevMan 5.3 and Stata 15.1 were used for Meta-analysis. Results: A total of 17 literatures were included involving 1 421 subjects. Results of Meta-analysis showed that OR of the correlation between methylation of HPV16 LCR and CIN2+ was 1.56 (95%CI: 0.70-3.47). Subgroup analysis showed that methylation of the 5' terminal, enhancer and promoter regions were not associated with CIN2+, while in four E2 binding sites (E2BS), the methylation of E2BS1, E2BS3 and E2BS4 increased the risk of CIN2+, with the ORs of 3.92 (95%CI: 1.92-7.99), 10.50 (95%CI: 3.67-30.04) and 3.65 (95%CI: 1.58-8.41), respectively. However, subgroup analysis on E2BS2 was not performed due to the limitation of the number of literatures. According to the different sources of population, the risk of CIN2+ in Chinese population was associated with methylation of HPV16 LCR (OR=2.14, 95%CI: 1.31-3.50). There was a correlation between the risk of CIN2+ and HPV16 LCR methylation in the population with pyrosequencing of HPV16 LCR, and OR was 1.75 (95%CI: 1.03-2.98). Conclusion: The risk of CIN2+ is correlated with the methylation of E2BS in HPV16 LCR, which can be used as potential biomarkers.
Female ; Humans ; Methylation ; Human papillomavirus 16/genetics* ; Asian People ; Uterine Cervical Neoplasms ; Uterine Cervical Dysplasia