1.Research progress of apoptosis pathways and caspases as therapeutic targets involved in Alzheimer′s disease
Wenbao WU ; Qinghong KONG ; Xiangxu KAN ; Guanlin WANG ; Kwenjen CHANG
Chinese Pharmacological Bulletin 2015;(11):1496-1501
Alzheimer′s disease ( AD) is a type of neurodegener-ative disease. Recent studies indicate that neuronal degeneration and loss triggered by tau, APP and Aβare the probable risks for AD. Neurofibrillary tangles are formed after tau truncated by ac-tivated caspases and subsequently induced tau aggregates, which causes neuronal degeneration and loss. In addition, caspases are crucial components in the biological functioning in the apoptosis pathways. Apoptosis pathway involves activation of upstream ini-tiator caspase-8 and downstream executor caspase-3/-6/-7. After the actions of β- and γ-secretase, APP transforms into sAPPβand Aβ40/42 . Aggregated Aβ42 can activate apoptosis pathway through DR4/5 interaction. C-APP is truncated into C31 frag-ments by caspases and cell apoptosis is facilitated. N-APP, a product of sAPPβhydrolysis, can promote the abnormal develop-ment of neurons mediated by DR6. Caspase activates γ-secre-tase-activating protein to regulate activity ofγ-secretase, and the production of C31 and Aβ40/42 , which, then, causes the occur-rence of AD. This brief review summarizes the specific roles of caspases and the concerning apoptosis pathways on the mecha-nisms of neuronal degeneration and loss, and how they impact the occurrence of AD in the hope of uncovering additional poten-tial therapeutic targets that can be employed in drug development and clinical therapy for AD.
2.Capillary GC Determination of Fentanyl in Human Plasma
Yuansheng LIU ; Yulian WU ; Qinghong KONG ; Xinhua WANG
Academic Journal of Second Military Medical University 1985;0(06):-
A GC method is described for measuring fentanyl in man plasma. Fentanyl was extracted at basic pH with cyclohexane-isobutyl alcohol (197:3) with Ro21-2212 added as internal standard and fentanyl derivative as earner. The drug was back-extracted in H2SO4, then the extract was made basic and recxtracted with ethyl ether-dichloromethane (9:1). The organic phase was evaporated at 40℃ under N2 and the residue was dissolved in ethanol. A. portion (2?l) was analyzed on a wide-bore capillary column (10 m ? 0.53 mm) of HP-1 (2.65 ?m), operated at 255℃ with N2 as carrier gas (8 ml/min) and N -P detector. The calibration graph was linear within the ranges of 0.25-100 ng/ml with a corelation coefficient of 0.9996 and the detected limit was 0.2 ng/ml. Mean recovery was 99.02% ? 6.81%. The coefficient of variation for the within- and between-run were all less than 8%. No interference was found from endogenous compounds, metabolites of parent drug or other commonly used drugs. The method was applied to therapeutic drug monitoring and pharmacokinetic studies.
3.Association between ankylosing spondylitis and HLA-B27 gene in Jiangxi province
Qinghong HU ; Chengyu YI ; Yan PENG ; Minggui LIU ; Yunyuan KONG
Chinese Journal of Tissue Engineering Research 2009;13(46):9183-9186
OBJECTIVE:To study the relevance between HLA-B27 gene and ankylosing spondylitis in Jiangxi province,and to discuss the diagnostic significance to ankylosing spondylitis.METHODS:A total of 1246 patients with suspected ankylosing spondylitis and related diseases were collected from the First Affiliated Hospital of Nanchang University from October 2007 to December 2008.Among all cases,323 were diagnosed as ankylosing spondylitis,and other 923 were rheumatoid arthdtis or related diseases.A total of 135 healthy subjects were collected as control group.Sequence-specific primer-polymerase chain method(PCR-SSP)was used to detect HLA-B27 gene in 1246patients and 135 healthy controls.The distribution of HLA-B27 gene,correlation between HLA-B27 gene and age,and relation between ankylosing spondylitis and HLA-B27 gene were studied.RESULTS:Total positive rate of HLA-B27 gene was 32.5%in 1246 patients with suspected ankylosing spondylitis.3.7%in 135healthy controls.and 91.6%in 323 patients with ankylosing spondylitis,respectively.The positive rate and incidence rates of male were significantly higher than female(P<0.01)and mainly concentrated in the age of adolescence.The sensitivity of HLA-B27 genewas 91.64%and the specificity was 88.19%in patients with ankylosing spondylitis.CONCLUSION:HLA-B27 gene was highly correlated with ankylosing spondylitis in Jiangxi province,which was the same as other regions,suggesting that HLA-B27 gene is significance for diagnosis of ankylosing spondylitis in an eedy phase.
4.Evaluation of antinociception, tolerance and withdrawal abstinence of opioid receptor triple agonist KUST201 in rats
Jiuling LI ; Qinghong KONG ; Jie YU ; Shoupu YI ; Yamin LI ; Guanlin WANG ; Yuehai SHEN ; Kwenjen CHANG
Chinese Pharmacological Bulletin 2016;32(5):652-657,658
Aim To investigate the antinociception, tolerance and withdrawal abstinence of δ/μ/κ opioid receptor triple agonist KUST201 ( DPI-125 ) in rats. Methods Male Sprague-Dawley rats were used to de-termine the time course of analgesic effects and ED50 effects of co-administration of naltrindole were assessed as well. In withdrawal experiments, KUST201 was ad-ministrated twice daily for 3 d with increasing doses each day. On the 4th day, the rats were given a single dose, challenged with naloxone 3 h later, and signs of abstinence were monitored. Results The ED50 values of KUST201 were 0. 34 mg·kg-1 in tail-pinch test and 0. 68 mg · kg-1 in hot-plate test. The antinociception actions of KUST201 started to decrease 1 h after ad-ministration, and disappeared after 2 h. In chronic tol-erance experiments, the antinociception actions started to decrease on d 3 , and completely disappeared on d 7 . Naltrindole could reduce the antinociceptive action of KUST201. In withdrawal experiments, abstinence scores increased significantly in the dose range between 2~8 times of tail-pinch ED50 . Conclusion Compared with previously reported δ/μ/κ triple agonist DPI-3290 , KUST201 exhibits similar antinociceptive effects in rats. The chronic tolerance to KUST201 actions de-velops less quickly, but the abstinence scores of KUST201 are slightly higher. The activation of δ-opi-oid receptor can synergistically enhance the antinoci-ception mediated by μ-receptor.
5.Problems and suggestions in the implementation of drug centralized volume-based procurement policies in the hospitals
Weihua KONG ; Qi QIAO ; Guoqiang LIU ; Nan CHEN ; Chengwu SHEN ; Qi CHEN ; Feng QIU ; Jianhua WANG ; Ling JIANG ; Qinghong LU ; Junyan WU ; Yafeng WANG ; Likai LIN ; Jiajia FENG ; Hong CHENG
Chinese Journal of Hospital Administration 2024;40(7):535-540
Objective:To explore the challenges in the implementation of drug centralized volume-based procurement policies in hospitals and propose corresponding optimization suggestions.Methods:From August to December 2023, a purposive sampling was conducted to select 11 pharmaceutical experts from tertiary hospitals in China for Delphi method. The survey content included " policy recommendations for promoting the acceleration and expansion of national drug centralized procurement and retaining surplus medical insurance funds for centralized procurement" .Results:Survey participants gave feedback on a set of existing problems found in the implementation of drug centralized procurement policies and proposed corresponding optimization methods. Kendall′s W coefficient of the specialist consultation was 0.332( P<0.05), demonstrating good consistency and concentration of the expert opinions. Among the problems, the score of drug supply guarantee was the highest(mean value of importance was 4.45). At the same time, the recommendation of strengthening monitoring and early warning, coordination and dispatch, and effectively ensuring the supply of centralized drug procurement had the highest score and concentration(mean value of importance was 4.91, coefficient of variation was 0.06). Conclusions:Through Delphi method, this study revealed issues and optimization methods in the implementation of drug centralized procurement policies in hospitals. The findings could provide valuable insights for improvements in the pharmaceutical sector and future policy adjustments.