Objective To study the level changes of matrix metalloproteinase-9 (MMP-9)and its clinical significance in patients with progressive ischemic stroke(PIS).Methods 136 cases of acute ischemic stroke including 46 cases of PIS and 90 cases of non-PIS,were studied.56 healthy subjects were selected into control group.MMP-9 level was measured by ELISA at 2,7 and 14 day after admission.The neurologic dysfunction score was observed.Results The MMP-9 level was ( 249.43 ± 63.76)μg/L,( 271.50±72.08 )μg/L,and (183.20 ±66.69)μg/L in PIS group,while it was (158.81±49.18 )μg/L,( 188.67±57.96 )μg/L,and ( 93.86 ±22.16)μg/L in non PIS group and was (88.60±15.93 )μg/L in control group at 2,7 and 14 days of admission.The MMP-9 level of PIS group at 2,7 and 14 day and the level in non PIS group at 2 and 7 day were higher than that of control group(P＜0.01 ).The MMP-9 level of PIS group was higher than that of different phrase of PIS group (P＜0.01 ).Linear X2 showed that the increase of MMP-9 level would increase the risk of ischemic stroke progression( X2=38.96,P＜0.01 ).Conclusion The remarkable increase of MMP-9 in patients with progressive ischemic stroke may be the indepent risk factor of the progression of ischemic stroke.

Objective To investigate Smoothened (Smo) expression in endothelial cells of synovial tissues in active rheumatoid arthritis (RA),and the expression of Sonic Hedgehog (Shh) signaling pathwayassociated factors after TNF-α treatment in EA.hy926 cells,and the effects of specific inhibitor of Smo (cyclopamine) on the apoptosis of EA.hy926 cells.Methods The Smo expression in endothelial cells in synovial tissue from 4 RA patients and 4 patients with traumatic or meniscal injury (with no arthritis,act as control group) were detected by immunohistochemistry assay.EA.hy926 cells were treated with different concentrations of TNF-α or TNF-α together with different concentrations of cyclopamine,and Shh,Ptch1,Smo,Gli1 mRNA expression levels were detected by real time-PCR.EA.hy926 cells were co-cultured with three different concentrations of cyclopamine for 24 hours before the addition of TNF-α and ActinomycinD (ActD).The cell survival rate was detected using CCK-8,and the population of apoptotic cells was detected using a flow cytometry.T-test and one-way ANOVA were used for statistical analysis.Results The positive expression rate of Smo in endothelial cells of synovial tissue in RA group was (81±23)％,which was higher than that in the control group (20±17)％ (P＜0.05).After being treated with TNF-α,the expressions of Shh and Smo mRNA in EA.hy926 cells increased,while the expression of Gli1 mRNA decreased (P＜0.05),and the expression of Ptch1 mRNA did not change significantly (P＞0.05).The expressions of Shh,Smo and Gli1 mRNA were down-regulated (P＜0.05).EA.hy926 cells treated with different concentrations of cyclopamine (2,4 and 8 μmol/L) showed a significant decrease in cell viability,in cell survival rates (57±6)％,(44±8)％ and (32±5)％ compared with that of TNF-α/ActD group (64±6)％ (P＜0.05),and cell apoptosis rates [(12.4±3.3)％,(14.5±2.7)％ (15.7±2.4)％] compared with that of TNF-α/ActD group (7.1±1.3)％ (P＜0.05).Conclusion Shh pathway is activated in endothelial cells of synovial tissue in active RA.The apoptosis in endothelial cells is promoted after cyclopamine treatment.Shh pathway may play an important role in the antiapoptotic regulatory mechanism of endothelial cells.

ObjectiveTo understand intensive care unit （ICU） doctors’ opinions and suggestions on implementing palliative care， and provides a reference basis for the implementation of palliative care in Chinese ICU. MethodsA purposive sampling technique was used to conduct one-on-one semi-structured interviews with 11 ICU doctors. Colaizzi’s phenomenological analysis method was utilized to code， classify， interpret， and comprehensively analyze the interview data. ResultsA total of 4 themes and 18 sub-themes was extracted， including cognitive biases toward palliative care， the belief that implementing palliative care in the ICU has significant humanistic implications （palliative care practice is the most perfect embodiment of medical humanities， palliative care in the ICU can alleviate patient pain and reduce invasive operations， palliative care can achieve comfortable care for ICU patients， palliative care focuses on maintaining the dignity of ICU patients， palliative care can pay attention to the inner voice of ICU patients， and implementing palliative care will help to more effectively allocate resources）， difficulties faced by ICU in carrying out palliative care （lack of clarity in relevant policies at the legal level， closed management environment in the ICU， insufficient manpower in the ICU and lack of palliative care professional team， inadequate understanding of ICU patients’ families， lack of death education， not included in medical insurance payments， and lack of communication skills of young doctors）， strategies to promote the development of palliative care in the ICU （ICU palliative care can be piloted first， the development of ICU palliative care screening tools will help with the development of palliative care， the palliative environment and the handling of death procedures can be further optimized， and the application and implementation of scientific methods to shorten the gap between evidence and practice of palliative care）. ConclusionsThe integration of palliative care and ICU in China is still blank. The significance of implementing palliative care in ICU should be emphasized， ICU doctors’ knowledge and skills of palliative care should be improved from multiple perspectives， patient preference should be emphasized to improve the knowledge and acceptance of palliative care of ICU patients’ families， and the promotion of palliative care in ICU clinical practice should be pioneered and piloted.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.