In recent years, the targeted protein degradation technology has developed quickly, with proteolysis-targeting chimera (PROTAC) as the best-known strategy through exploring the ubiquitin-proteasome system. A number of new targeted protein degradation strategies have been emerging to expand the scope of protein degradation technology, including lysosome-targeting chimeras (LYTACs), autophagy-targeting chimeras (AUTACs), autophagosome-tethering compounds (ATTECs) and chimeras based on chaperone-mediated autophagy (CMA). The emerging methodologies have explored another important protein degradation system in eukaryotes-lysosomal systems, such as the endosome-lysosome pathway and the autophagy-lysosome pathway. This review summaries the mechanisms and features of different strategies for targeted protein degradation, with a special emphasis on the new targeted protein degradation technologies, such as their current status, advantages and limitations.

Objective To study the state and trends of Kesan disease in Henan province from 2004 to 2009. Methods Surveillance sites were selected: Guxian village of Luoning country from 2004 - 2007, Zuyang town of Lingbao city in 2008, and Shahe village of Lushi country in 2009. All residents of surveillance sites were examined by clinical and electrocardiogram, and suspected patients were inspected by chest X-ray to measure ardiothoracic ratio. Hair and wheat flour samples were collected and selenium levels were detected with hydride generation atomic fluorescence spectrometry. Results From 2004 to 2009, a total of 4034 people were examined.The numbers of chronic and latent KSD patients were 21 and 75 cases,respectively, and the incidence rates were 0.52%(21/4034) and 1.86%(75/4034), respectively . The number of abnormal electrocardiogram was 751 cases, and the incidence rate was 18.62%. The highest proportion of abnormal electrocardiogram was ST-T changes,accounting for 24.63%(185/751), followed by high-voltage, accounting for 18.11%(136/751), and left ventricular accounting for 13.85% (104/751). Sixty-one grain samples were collected and the wheat flour selenium level was averaged 0.034 mg/kg. Thirty hair samples were collected and the selenium median was 0.285 mg/kg. Conclusions The state of Keshan disease is in a steady state in Henna province, but higher rates of abnormal electrocardiogram is a serious problem and should be studied and prevented.

Objective To understand Kaschin-Beck disease(KBD) status in Henan Province and provide the basis for the further prevention and treatment of KBD. Methods Children aged 7 to 12 in 3 villages(Yaodian, Miaowa and Zhuyang) with the same environment such as topography, physiognomy,production mode and living habits in Shan County and Lingbao City were selected to undertake KBD clinical examination in 2008, X-ray examination of right hand and child hair samples and food samples were collected to determine the content of selenium. Selenium was determined using 2,3-Diaminonaphthalene method. Adults who were 16 years or older in 5 counties(Luoning, Lingbao, Mianchi, Shah and Lushi) were selected and examined for KBD. Results One hundred and ninty children aged 7 to 12 were clinically examined and clinical KBD were found, whereas 3 children were diagnosed as KBD by X-ray examination, the positive rate was 1.58% (3/190). All 20 521 adults were clinically examined and KBD prevelance rate was 6.10%(1251/20 521), including degree Ⅰ (3.97%,814/20 521), degree Ⅱ (1.77%, 364/20 521 ), degree Ⅲ (0.36%, 73/20 521). The average selenium contents in hair and food samples were (0.319±0.128)mg/kg and (0.031±0.009)mg/kg, respectively. Conclusions Child KBD in Henan Province is under control or almost under control, whereas the prevalence of adult KBD was relatively serious, which suggested that secondary prevention with the objective of clinically treating KBD patients should be strengthened.

Objective:To investigate the expression of wild type estrogen receptor(wER)and the ex-on-5 deleted ER(variant ER,vER)in human hepatocellular carcinoma(HCC)samples,and thereafteranalyze the possibility of HCC treatment by endocrine therapy.Methods:The mRNA expressions of wERand vER were analysed from 28 cases of HCC by RT-PCR.The expression of ER at the protein level wasdetected by immunohistochemistry(IHC).Results:IHC results showed that 39.3% of the HCC speci-mens expressed ER.The mRNA of wER was detected in 89.3%(25/28)of the HCC specimens whilethat of vER was detected in 96.4%(27/28).Twenty four out of 28 HCC cases(85.7%)expressedboth wER and vER.One out of 28 patients(3.5%)expressed only wER whereas 3 patients out of 28(10.7%)expressed vER only.Conclusion:Ninety six percent(27/28)of the HCC patients expressedvER,which suggests that the expression of vER is an important event in the development of HCC.

ObjectiveTo investigate the effect and underling mechanism of water-soluble CO-releasing molecules (CORM-3)on the alleviation of allograft rejectionafter mouse kidney transplantation.Methods A mice kidney transplantation model was established using C.FVB-Tg (Itgax-DTR/GFP)57Lan/J or C57BL/6J (H-2Kb) mice as donors,and Balb/c (H-2Kd) mice as recipients.After donor nephrectomy,kidney was preserved in UW solution which contained CORM-3 or iCORM (inactive CO-releasing molecules) for 24 h in 4℃.Recipient survival after removal of both na? ve kidneys,serum creatinine as well as graft histology was observed.In the C.FVB-Tg(ItgaxDTR/GFP) 57Lan/J donors,rDCs were acquired in vitro and selected by magnetic cell sorting (MACS) after graft nephrectomy.The expression of activation markers,CD80 and CD86,on rDC was assessed by using flow cytometry.ResultsThe graft medium survival time was 40.5 days in the iCORM group and 70 days in the CORM-3 group respectively (P＜0.05).CORM-3 preserved the graft function as shown by significantly lower serum creatinine (P＜0.05; or P＜0.01) and alleviated graft pathology injury.Diffuse infiltration of mononuclear cells in the interstitial tissues,moderate tubulitis and partial glomerular sclerosis were found in the iCORM graft kidney,while the CORM-3 graft kidney displayed almost normal histology.Meanwhile,CORM-3 suppressed the expression of CD80 and CD86 in donor-derived rDC.ConclusionCORM-3 can alleviate allograft rejection,prolong the graft survival,and improve kidney function in mouse kidney transplantation,probably via inhibiting rDC activation.

To evaluate the regulating effect of Buyang Huanwu decoction and its simple prescription (Naojian tablet) on CDK4/Cyclin D1 expression in hippocampus tissues of rats with cerebral ischemia, SD rats were divided into the sham-operation group, the model group, the Buyang Huanwu decoction group (ig, 3.15 g · kg⁻¹) and the simple prescription group (ig, 2.41 g · kg⁻¹). Each group was further divided into five subgroups based on time points after the administration, i. e. 1 d, 3 d, 7 d, 14 d and 28 d, respectively. CDK4/Cyclin D1 expressions of the group at different time points were examined by using immunohistochemistry and real-time qPCR. According to the results, the cerebral ischemia model group showed higher CDK4/Cyclin D1 expression than the sham-operation groups (P < 0.05), suggesting that the cell cycle signal pathway would be activated by the cerebral ischemic injury. Both Buyang Huanwu decoction and simple prescription groups showed significantly lower cyclin expression than the model group at 3 d, 7 d, 14 d, 28 d (P < 0.05), indicating both Buyang Huanwu decoction and its simple prescription could play the neuroprotective effect through the cell cycle signal pathway.
Animals ; Brain Ischemia ; drug therapy ; genetics ; metabolism ; physiopathology ; Cell Cycle ; drug effects ; Cyclin D1 ; genetics ; metabolism ; Cyclin-Dependent Kinase 4 ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Male ; Rats ; Rats, Sprague-Dawley

BACKGROUND:The majority of studies focus on the lesions of spinal cord injury, while little evidence is available on the change of morphology and structure of distal nerve, muscle and motor endplates fol owing spinal cord injury.
OBJECTIVE:To investigate the time window change of the morphology of motor neurons and skeletal muscles caudal to the lesion after spinal cord injury in rats.
METHODS:Fifty healthy adult Sprague-Dawley rats were randomly divided into three groups:control group (n=5;without treatment), sham operation group (n=10), and spinal cord injury group (n=35). The sham operated rats only received laminectomy. In the spinal cord injury group, rats were subject to complete T 10 spinal cord injury by total laminectomy and cord transverse resection. Then the morphological change including sciatic nerve, motor endplate and median gastrocnemius was observed for each group at 1, 2, 4, 12, 24 weeks after injury.
RESULTS AND CONCLUSION:(1) The myelin sheath layers of sciatic nerve were separated partial y at 4 weeks in rats with spinal cord injury, the myelin sheaths were fragmented with the regeneration of thin-myelinated and unmyelinated axons at 12 weeks. There was a decrease in myelinated axons and an increase in thin-myelinated and unmyelinated axons at 24 weeks. (2) The synaptic gutters of motor endplate, the presynaptic and postsynaptic membrane and synaptic space were distinct at 4 weeks in rats with spinal cord injury, the degenerated motor endplates coexsisted with the intact ones at 12 weeks. The motor endplate disappeared at 24 weeks. (3) There was a slight decrease in muscle cross-sectional area at 2 weeks in rats with spinal cord injury, but no structural change was found, the membrane of myocytes was partial y weakened at 4 weeks, the border of myocytes was obscure with hyperplasia of connective tissue at 12 weeks, and myocytes gathered and in fusion at 24 weeks. As natural history of completely transected spinal cord injury in rats, there were significant changes in morphology of peripheral nerve, motor endplate and skeletal muscles caudal to the lesion at 12 weeks, and the changes were destructive at 24 weeks.

Objective To investigate the effectiveness and safety of ballon-assisted surgical wrapping-clipping for the treatment of blood blister-like aneurysms (BBA) of internal carotid artery. Methods The clinical data of 9 patients with BBA of internal carotid artery who were treated by ballon-assisted surgical wrapping-clipping from August 2011 to June 2016 were retrospectively analyzed. Results All 9 patients were successfully treated with surgical wrapping-clipping in ballon-assisted technique. The BBA had no rebleeding.Nine cases were followed up clinically for six months. Digital subtractive angiography demonstrated no aneurysm in these patients, and showed no stenosis in the parent artery. Conclusions Ballon-assisted surgical wrapping-clipping in the treatment of BBA is effective and safety. It may help to reduce the risks of BBA rebleeding and recurrence.

?AIM:To evaluate the objective visual quality of patients who underwent corneal cross-linking for the keratoconus using double-pass analysis system.? METHODS: Advanced keratoconus patients who underwent UV - riboflavin corneal cross - linking from January to July 2015 were included. The outcomes of their objective scattering index ( OSI ) , predicted visual acuity ( VA ) , the cut - off frequency of modulation transfer function ( MTF cut- off ) , the Strehl ratio ( SR ) were compared before and 6mo after corneal cross-linking.?RESULTS: A total of 13 patients ( 16 eyes ) were included. There was no statistically significant difference between pre- and 6mo postoperative data in uncorrected visual acuity, best corrected visual acuity, refractions and mean value of Sim-k (P>0. 05). Non-invasive average tear film break up time ( NIAvg-BUT ) detected by the Sirius system decreased after corneal cross-linking ( P<0. 05 ) . Using double - pass analysis system, no statistically significant change was found in MTF cut off, Strehl Ratio, OSI before and after treatment(P>0. 05). Tear Film Analysis Mean OSI increased at 6mo postoperatively (P<0. 05).? CONCLUSION: The subjective visual quality isn’t effected by corneal cross-linking. The tear stabilities of patients are influenced by these operations at 6mo postoperatively. More observations on long-term effect are needed to be taken in the future.

Objective To explore the clinical application and significance of polymerase chain reactio n(PCR) in checking human cytomegalovirus (HCMV)in cerebral palsy children. Methods Collecting urine and serum of 56 cerebral palsy (CP) children,using PCR to detec t CMV DNA from urine,isolate CMV from urine,and indirect enzyme-linked immuno so rbent assay(ELISA) detecting CMV IgM、IgG of serum.Results In 56 cases,53.6%cases were CMV DNA positive,there were 9 cases CMV isolation,o bserving CMV characteristic cytopathic effect (CPE) and the positive value of se rum CMV IgM、IgG was 12.5%,37.5% respectively.The positive value in isolation o f the virus and CMV IgM was 100%,10% corresponding with that of CMV DNA.Comp ared the 2 former with the latter,it was significant(P0.05).Conclusions Using PCR can detect CMV DNA from CP children with CMV infection quickly.It can apply in detecting CMV in CP and provide credible evidence for intervention as f ar as early in children with CP. J Appl Clin Pediatr,2005,20(2):157-159