2.Advances on Keap1-Nrf2 protein-protein interaction inhibitors and degraders
Jian-yu YAN ; Guo-dong LIU ; Zhen-yuan MIAO ; Chun-lin ZHUANG
Acta Pharmaceutica Sinica 2022;57(10):2932-2948
Oxidative stress is a redox imbalance in the body, which is one of the important factors leading to tissue damage and diseases. The nuclear factor E2-related factor 2 (Nrf2)-Kelch like ECH-associated protein 1 (Keap1) signaling pathway is not only an important defense system against oxidative damage, but also one of the key signaling pathways of the antioxidant capacity. Numerous studies have shown that targeting the Keap1-Nrf2 signaling pathway to activate Nrf2 has become an effective strategy for the treatment of oxidative stress and related diseases. Using small molecules to directly block the Keap1-Nrf2 protein-protein interaction (PPI) is one of the important directions for activating Nrf2 and exerting the cytoprotective effect, which can avoid the potential side effects of covalent modification of Nrf2. On the other hand, the Keap1 is an efficient E3 ubiquitin ligase that has been used in the design of proteolysis targeting chimeras (PROTACs). This review summarizes the research progresses of Keap1-Nrf2 protein interaction inhibitors and degraders based on the Keap1 E3 ubiquitination system in recent years.
3.Expression of PTEN protein and its correlation with p27kip1 and cyclin D1 expression in primary breast cancer.
Qin LIN ; Yan-zhen ZHUANG ; Dong-po XU ; Jian-xin YE ; Pei-qiong CHEN
Chinese Journal of Oncology 2003;25(3):246-249
OBJECTIVETo study the expression of phosphatase and tensin homology deleted on chromosometen ten (PTEN) protein, a tumor suppressor gene in breast cancer and its correlation with p27(kip1) and cyclin D1 expression.
METHODSPTEN protein expression, p27(kip1) and cyclin D1 protein expression were detected by immunohistochemical method in paraffin sections from 61 women with primary breast cancer. PTEN protein expression was compared with clinico-pathologic parameters as related to p27(kip1) and cyclin D1.
RESULTSPTEN, being shown in the cytoplasm, was negative in 6.6% (4/61), reduced in 41.0% (25/61) and positive in 52.5% (32/61) samples. PTEN expression level was correlated with axillary lymph node status, loss of estrogen receptor stain, recurrence and metastasis. On univariate analysis, the disease-free survival rate of patients with higher PTEN expression (> 50% cells stained) was better than those with lower expression (P = 0.0101). However, there was no correlation between p27(kip1), cyclin D1 expression or PTEN expression.
CONCLUSIONPTEN, its lower expression being correlated with poor outcome of breast cancer patients, plays a prominent role in breast cancer. p27(kip1) or cyclin D1 may not be the primary downstream genes of PTEN in breast cancer.
Adult ; Aged ; Breast Neoplasms ; chemistry ; mortality ; pathology ; Cyclin D1 ; analysis ; physiology ; Cyclin-Dependent Kinase Inhibitor p27 ; Female ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins ; analysis ; physiology ; Lymphatic Metastasis ; Middle Aged ; PTEN Phosphohydrolase ; analysis ; physiology ; Prognosis
4.Application of the second metatarpophalangeal joint by traction prolong transplant repair the defects in the metacarpophalangeal joint
Jian-Wen LIAO ; Ze-Hua CHEN ; Jia-Chuan ZHUANG ; Jia-Jun ZHANG ; Zheng LI ; Shao-Xiao YU ; Zhen-Wei ZHANG ;
Chinese Journal of Microsurgery 2006;0(05):-
Objective Application of the second metatarpophalangeal joint by traction prolong trans- plant repair the defects in the metacarpophalangeal joint,reconstruct the function of it.Methods By means of the apparatus to prolong finger in advance,then transplant the second metatarpophalangeal joint to recon- struct metacarpophalangeal joint for seven cases of obsolete defects in the metacarpophalangeal joint.Results The average of finger prolong was 2.6 cm,consultation from 1 to 4 years.average 2.5 years,thai the trans- plant joints have all survived and osteal concrescence.Through the criterion Chinese Medical Association,good rate was 85.7%. Conclusion It' s a good method to repair obsolete defects in the metacarpophalangeal joint by transplant traction prolong of the second metatarpophalangeal joint.
5.Analysis of 41 cases of neurosyphilis presenting with cerebral infarction
Jian-Zhuang ZHEN ; An-Hui HONG ; Huang-Ning ZHAO
Chinese Journal of Neuromedicine 2009;8(6):613-615
Objective To investigate the clinical characteristics of neurosyphilis presenting clinically with cerebral infarction and study its treatment and prognosis. Methods A retrospective analysis was conducted in 41 patients with neurosyphilis who presented clinically with cerebral infarction. The clinical manifestations, neurological deficit scores, activity of daily life (ADL) scores, mental scale scores, and laboratory and imaging examination results of the patients were analyzed. Results Of the 41 patients, 23 exhibited reduced intelligence, 30 had limb paralysis, 8 had limb numbness, 2 complained of dizziness, and 1 experienced epileptic attacks. Head magnetic resonance imaging (MRI) revealed the presence of brain atrophy and multiple infarction foei without obvious space-occupying effect of cerebral edema in these patients. All the patients showed positive results of serum and cerebrospinal fluid Treponema pallidum hemagglutination assay (TPHA). After treatment with high-dose penicillin, 95.1% of the patients had improvements of the clinical symptoms. Conclusion The diverse clinical manifestations of neurosyphilis often result in misdiagnosis of the disease. Patients with neurosyphilis show multiple cerebral infarction foci and cerebral atrophy without obvious space-occupying effect on MRI. Penicillin can be an effective treatment in such cases, which generally have low rate of negative TPHA within 3 months. Such patients have more favorable clinical outcomes than those with common cerebral infarction, but poor prognosis is indicated in cases with concurrent extensive cerebral infarction.
6.Research Progress of Pathology of Gout and Clinical Treatment with Traditional Chinese and Western Medicine
Jian-long SHU ; Feng-zhen LI ; Yu-wang QIN
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(2):218-227
With the improvement of people's living standard and the change of dietary structure, the prevalence of gout has increased gradually with the increased intake of protein, sugar and fat. There has been a positive correlation between gout and age, and the age of onset decreased gradually. The inflammation induced by sodium urate crystal is the pathological basis of gout, which activates innate immunity, releases many kinds of inflammatory mediators, such as interleukin(IL)-1
9.Analysis of concurrent intravertebral vacuum sign in thoracolumbar fractures after posterior internal fixation.
Xiao-dong ZHANG ; Jian-li FANG ; Ru-jie ZHUANG ; Hai-feng XIE ; Zhen-chuan MA
China Journal of Orthopaedics and Traumatology 2011;24(7):557-559
OBJECTIVETo investigate the importance of TLICS classification to surgical options of thoracolumbar fractures by analyzing the cause of intravertebral vacuum sign, vertebral collapse and vertebral pseudarthrosis.
METHODSFrom January 2006 to December 2010, the clinical data about 15 patients with postoperative complications by thoracolumbar fracture after posterior internal fixation were retrospectively analyzed. There were 9 males and 6 females, ranging in age from 18 to 75 years, with an average of 54.6 years. Of them, fracture site in T12 was 7 cases, L1 was 5 cases, L2 was 3 cases; compression fractures was in 12 cases and burst fracture was in 3 cases; according to classification of TLICS, 12 cases were of type I ,3 cases of type III. And the causes of complications after posterior fixation were analyzed according clinical manifestation and imaging finding combined with review literatures.
RESULTSAfter 10 to 20 months following-up (with average of 15 months), loss of vertebral height found in 9 cases (4 cases existed vertebral collapse, as well as 3 cases occurred screw loosening) and Intravertebral Vacuum Sign appeared in 6 cases.
CONCLUSIONIn order to avoid the vertebral vacuum and fixation failure, the clinical data of patients should be roundly and carefully evaluated, surgical indications should be strictly controlled and the surgical approach should be selected according to correct classification. Particularly, the reconstruction of the stability of former spinal column shoud be paid more attention.
Adolescent ; Adult ; Aged ; Female ; Fracture Fixation, Internal ; adverse effects ; Humans ; Lumbar Vertebrae ; diagnostic imaging ; injuries ; surgery ; Male ; Middle Aged ; Postoperative Complications ; diagnostic imaging ; etiology ; Retrospective Studies ; Spinal Fractures ; diagnostic imaging ; surgery ; Thoracic Injuries ; diagnostic imaging ; surgery ; Tomography, X-Ray Computed ; Young Adult
10.Post-stroke shoulder-hand syndrome treated with floating-needle therapy combined with rehabilitation training: a randomized controlled trial.
Zhao-Hui ZHOU ; Li-Xing ZHUANG ; Zhen-Hu CHEN ; Jian-Ying LANG ; Yan-Hui LI ; Gang-Hui JIANG ; Zhan-Qiong XU ; Mu-Xi LIAO
Chinese Acupuncture & Moxibustion 2014;34(7):636-640
OBJECTIVETo compare the clinical efficacy in the treatment of post-stroke shoulder-hand syndrome between floating-needle therapy and conventional acupuncture on the basis of rehabilitation training.
METHODSOne hundred cases of post-stroke shoulder-hand syndrome were randomized into a floating-needle group and an acupuncture group, 50 cases in each one. The passive and positive rehabilitation training was adopted in the two groups. Additionally, in the floating-needle group, the floating-needle therapy was used. The needle was inserted at the site 5 to 10 cm away from myofasical trigger point (MTrP), manipulated and scattered subcutaneously, for 2 min continuously. In the acupuncture group, the conventional acupuncture was applied at Jianqian (EX-UE), Jianyu (LI 15), Jianliao (TE 14), etc. The treatment was given once every two days, 3 times a week, and 14 days of treatment were required. The shoulder hand syndrome scale (SHSS), the short form McGill pain scale (SF-MPQ) and the modified Fugl-Meyer motor function scale (FMA) were used to evaluate the damage severity, pain and motor function of the upper limbs before and after treatment in the two groups. The clinical efficacy was compared between the two groups.
RESULTSSHSS score, SF-MPQ score and FMA score were improved significantly after treatment in the two groups (all P < 0.01), and the improvements in the floating-needle group were superior to those in the acupuncture group (all P < 0.05). The total effective rate was 94.0% (47/50) in the floating-needle group, which was better than 90.0% (45/50) in the acupuncture group (P < 0.05).
CONCLUSIONThe floating-needle therapy combined with rehabilitation training achieves a satisfactory efficacy on post-stroke shoulder-hand syndrome, which is better than the combined therapy of conventional acupuncture and rehabilitation training.
Acupuncture Therapy ; instrumentation ; methods ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Reflex Sympathetic Dystrophy ; etiology ; rehabilitation ; therapy ; Stroke ; complications ; Treatment Outcome ; Young Adult