Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Objective:To investigate the routine ultrasonographic findings of fibrinous breast disease lesions , and to provide the basis for the differential diagnosis of fibrocystic breast disease lesions and breast cancer.Methods:The two-dimensional ultrasonography , color doppler flow and elastography of 166 lesions in 144 patients with fibrocystic breast disease confirmed by pathology in Peking University Shenzhen Hospital from January 2015 to February 2021 were retrospectively analyzed.Results:The ultrasonographic characteristics of fibrocystic breast disease lesions were as follows: 74.1%(123/166) lesions were hypoechoic, 57.2%(95/166)lesions were irregular, 49.4%(82/166) lesions were incomplete, 90.4%(150/166) lesions were parallel, 25.9%(43/166) lesions showed small cysts, 24.1%(40/166) lesions showed coarse calcification or fine calcification, 65.1%(108/166) lesions showed no change in posterior echo, 90.4%(150/166) blood flow was poor. The elastography score of 98.2%(162/166) lesions was 2-3 points.Conclusions:The ultrasonographic features of fibrocystic breast tumor are hypoechoic, irregular shape, incomplete edge, with fine or coarse calcification, which are easy to be misdiagnosed as breast malignant tumor. However, the former is characterized by parallel growth, small cyst in the interior, no change in posterior echo, lack of blood supply and soft texture, which provide important basis for clinical differential diagnosis.

Objective To explore the application of the 30°gradient clapboard storage rack for the specimen in the storage management of specimens in operating room.Method The the 30°gradient clapboard storage rack for the specimen was self-designed and applied in clinic based on a series of problems including that the specimen was deposited in plane container such as the large tray and there was easy not fixation fluid immerging into the specimen and there was fixation fluid leakage and so on. A total of 927 specimens of surgery deposited in the large tray before improvement (October 2014) was selected as control group. A total of 974 specimens of surgery deposited in the 30°gradient clapboard storage rack for the specimen after improvement (October 2015) was selected as observation group. And then, we compared the incidence that the fixation fluid didn't immerge into the specimen and there was fixation fluid leakage and specimen bag toppled and fell and the degree of satisfaction of doctors.Results The incidence that the fixation fluid didn't immerge into the specimen and specimen bag toppled and fell and there was fixation fluid leakage were 0.1%, 0.2%, 0.1% after using storage rack for the specimen lower than those (11.1% and 9.1% 5.5%) before using it. The fraction defective of specimen storagein observation group was 0.4% , the control group was 26.0%. The difference was significant(χ2=270.595,P<0.01). The degree of satisfaction of surgeons in observation group was 100.00%, the control group was 38%. The difference was significant (χ2=42.076,P<0.01).Conclusions The special purpose storage rack for the specimen satisfies the demands of surgical specimen storage. It can effectively guarantee that the fixation fluid immerge into the specimen, solve the phenomena that there is fixation fluid leakage, control the occupational exposure and environmental pollution and improve the quality of specimen storage.

Objective To investigate the characteristics of cognitive impairment and psychotic symptoms in general paresis of insane (GPI) before and after penicillin therapy, and explore factors that may predict the clinical outcomes. Methods Thirty patients with GPI were recruited. All GPI patients underwent a comprehensive neuropsychological assessment before receiving penicillin therapy, and returned for follow-up visits after 7 months. The severity of dementia was determined by Clinical Dementia Rating Scale (CDR), cognitive functions were assessed by Mini Mental State Examination (MMSE) and Alzheimer 's Disease Assessment Scale-cognitive subscale (ADAS-Cog), ability of daily living was assessed by Instrumental Activities of Daily Living Scale (IALD) and Physical Self maintenance Scale(PSMS), behavioral and psychological symptoms were assessed by Neuropsychiatric Inventory (NPI). Aqueous crystalline penicillin G 24 million units per day was administered as continuous infusion for 14 days, followed by benzathine penicillin 2.4 million units IM once per week for 3 weeks. Patients returned for follow-up visits after 7 months. Clinical outcomes were determined by the improvement of neuropsychological test scores at the end of the treatment. Grouped by CDR scores, changes in neuropsychological tests scores among different GPI groups were used to explore the correlation between severity of dementia and clinical outcomes. Univariate analysis and multivariate linear regression analysis were used to identify factors that may predict the clinical outcomes. Results (1)After penicillin therapy, GPI patients' MMSE scores(14.4± 6.9 vs.17.1 ± 9.1)and IADL scores(4.0(2.0, 5.0)vs.6.0(2.0, 7.3))both improved significantly(t=5.820, Z=3.710, P<0.01),while in ADAS-Cog, only factor scores of attention(1.5(0.7, 3.0)vs.1.5(0, 2.3))reduced significantly(Z=- 2.680, P<0.01). NPI's total scores(46.0 ± 27.1 vs.17.6 ± 15.4)and subscores of hallucination, delusion, agitation, depression, euphoria, disinhibition and irritability reduced significantly (Z=-4.940,-2.381,-2.504,-3.095,-2.492,-3.097,-2.527,-3.715, all P<0.05).(2) Grouped by the CDR scores, MMSE scores and IADL scores in very mild GPI group with CDR=0.5 improved significantly. In mild GPI group with CDR=1, significant changes were also found in all neuropsychological tests scores(MMSE,t=5.409, P<0.01), total scores of ADAS-Cog (Z=-2.366,P<0.05), IADL (Z=2.546, P<0.05), total scores of NPI (Z=-3.558,P<0.01), but except for PSMS. In moderate to severe GPI group with CDR>1,significant change was found only in total scores of NPI (t=-3.772,P<0.05). (3) Univariate analysis and multivariate linear regression analysis showed that improvement of MMSE scores after the treatment was significantly correlated with IADL scores and MMSE scores at baseline(β=0.541,P=0.004;β=0.364,P=0.044). Conclusions After penicillin treatment, GPI patients may improve in both cognitive function and psychotic symptoms but not in all the domains. Symptoms of anxiety, sleep/nigh-time behavior change, and apathy, as well as moderate to severe GPI patients may not benefit much from the treatment.

Objective To investigate the characteristics of cognitive impairment and psychotic symptoms in general paresis of insane (GPI) before and after penicillin therapy, and explore factors that may predict the clinical outcomes. Methods Thirty patients with GPI were recruited. All GPI patients underwent a comprehensive neuropsychological assessment before receiving penicillin therapy, and returned for follow-up visits after 7 months. The severity of dementia was determined by Clinical Dementia Rating Scale (CDR), cognitive functions were assessed by Mini Mental State Examination (MMSE) and Alzheimer 's Disease Assessment Scale-cognitive subscale (ADAS-Cog), ability of daily living was assessed by Instrumental Activities of Daily Living Scale (IALD) and Physical Self maintenance Scale(PSMS), behavioral and psychological symptoms were assessed by Neuropsychiatric Inventory (NPI). Aqueous crystalline penicillin G 24 million units per day was administered as continuous infusion for 14 days, followed by benzathine penicillin 2.4 million units IM once per week for 3 weeks. Patients returned for follow-up visits after 7 months. Clinical outcomes were determined by the improvement of neuropsychological test scores at the end of the treatment. Grouped by CDR scores, changes in neuropsychological tests scores among different GPI groups were used to explore the correlation between severity of dementia and clinical outcomes. Univariate analysis and multivariate linear regression analysis were used to identify factors that may predict the clinical outcomes. Results (1)After penicillin therapy, GPI patients' MMSE scores(14.4± 6.9 vs.17.1 ± 9.1)and IADL scores(4.0(2.0, 5.0)vs.6.0(2.0, 7.3))both improved significantly(t=5.820, Z=3.710, P<0.01),while in ADAS-Cog, only factor scores of attention(1.5(0.7, 3.0)vs.1.5(0, 2.3))reduced significantly(Z=- 2.680, P<0.01). NPI's total scores(46.0 ± 27.1 vs.17.6 ± 15.4)and subscores of hallucination, delusion, agitation, depression, euphoria, disinhibition and irritability reduced significantly (Z=-4.940,-2.381,-2.504,-3.095,-2.492,-3.097,-2.527,-3.715, all P<0.05).(2) Grouped by the CDR scores, MMSE scores and IADL scores in very mild GPI group with CDR=0.5 improved significantly. In mild GPI group with CDR=1, significant changes were also found in all neuropsychological tests scores(MMSE,t=5.409, P<0.01), total scores of ADAS-Cog (Z=-2.366,P<0.05), IADL (Z=2.546, P<0.05), total scores of NPI (Z=-3.558,P<0.01), but except for PSMS. In moderate to severe GPI group with CDR>1,significant change was found only in total scores of NPI (t=-3.772,P<0.05). (3) Univariate analysis and multivariate linear regression analysis showed that improvement of MMSE scores after the treatment was significantly correlated with IADL scores and MMSE scores at baseline(β=0.541,P=0.004;β=0.364,P=0.044). Conclusions After penicillin treatment, GPI patients may improve in both cognitive function and psychotic symptoms but not in all the domains. Symptoms of anxiety, sleep/nigh-time behavior change, and apathy, as well as moderate to severe GPI patients may not benefit much from the treatment.

Objective:To study the changes and significance of Th17 and Treg cells as well as their associated cytokines in pe-ripheral blood of patients with chronic hepatitis C and cirrhosis in order to investigate their role in the pathogenesis of chronic hepatitis C and hepatitis C cirrhosis. Methods:Flow cytometry and ELSIA assay were used to detect the expression ratio of Th17 and Treg cells and the serum levels of IL-10,TGF-β,IL-6 and IL-17 in peripheral blood of healthy human and patients with chronic hepatitis C and hepatitis C cirrhosis. Than we analyzed the differences of the above detection index between the healthy and patients with chronic hepatitis C and hepatitis C cirrhosis. Results:The expression ratio of Th17 cells (1. 33%±0. 30%) in peripheral blood of patients with chronic hepatitis C and IL-6[(8. 10±2. 42)ng/L] and IL-17[(16. 70±4. 73)ng/L] serum levels were significantly higher than those in the healthy (Th17:1. 14%±0. 19%) and IL-6[(1. 72±6. 70)ng/L],IL-17[(12. 29±1. 88)ng/L],P<0. 05;The expression ratio of Treg cells in peripheral blood of patients with hepatitis C cirrhosis and chronic hepatitis C patients was significantly higher than that in the healthy (6. 21%±0. 76%,5. 89%±0. 85% vs 5. 51%±0. 59% ),P<0. 05,The ratio of Th17/Treg in patients with cirrhosis was significantly lower than that in patients with chronic hepatitis C and the healthy(0. 19±0. 02 vs 0. 22±0. 03,0. 21±0. 03),P<0. 05;the levels of IL-1[(16. 21±3. 76)ng/L] and TGF-β[(5. 15±0. 83)ng/L] in peripheral blood of patients with hepatitis C cirrhosis were significantly higher than those in chronic hepatitis C[(14. 36±2. 78)ng/L;(4. 47±0. 87)ng/L] and the healthy[(14. 01±3. 01)ng/L;(4. 43±0. 98)ng/L)],P<0. 05. Conclusion:Th17 and Treg cells and their related cytokines involved in the process of chronicity of hepatitis C and cirrhosis,Th17 and Treg cells and their related cytokines in the treatment and prevention of chronicity of hepatitis C and cirrhosis may have important significance.

Objective:To study of change of Th17 cell and IL-17 caused by bacteria biofilm after infection.Methods: To detect biofilm formation ability of bacteria isolated from bronchus alveolus washing-water of patients;to detect expressing ratios of Th17 cells and IL-17 level in peripheral blood of patients and healthy person;to detect expressing ratios of Th17 cells and IL-17 level in bronchus alveolus washing-water of patients;to analyze the above data using SPSS17.0 software.Results: Expressing ratios of Th17 cells and IL-17 level in peripheral blood of patients infected by producing biofilm and non-producing biofilm bacteria and healthy person are respectively(0.59±0.18)%and(108.8±20.5)pg/ml,(0.58±0.18)%and(100.1±20.7)pg/ml,(0.55±0.17)% and(100.0± 21.4)pg/ml,they were not different among data from patients and healthy person,P>0.05,expressing ratios of Th17 cells and IL-17 level in bronchus alveolus washing-water of patients infected by producing biofilm and non-producing biofilm bacteria were respective (1.37±0.34)%,(157.4±30.8)pg/ml and(1.11±0.21)%,(136.2±24.3)mg/ml,the data between patients infected by producing biofilm and non-producing biofilm bacteria were distinctly different, P<0.05.Conclusion: Bacteria biofilm can cause Th17 cell expressing ratio and IL-17 level to become high in infected part,this may be mechanism that infection become chronic.

Objective To improve the quality of pressure steam sterilization, and ensure medical safety. Methods Sterilization time, temperature, pressure, and other real-time data during the process of the pressure steam sterilization were introduced into an electronic management system. The minimum threshold of eligible sterilization was set in the electronic management system in order to automatic identify the success of sterilization. An interlocking quality control chain was established. At the same time, the BD test results, key parameters of the sterilization process, chemical monitoring results, and biological monitoring results formed the quality control chain. The quality control chain actively controlled the quality of the whole process, and ensured products having been processed by qualified sterilization before distribution. Results In the past seven months, BD test was completed 636 batches. Two batches were intercepted for unqualified sterilization process, and 1 987 batches were completed sterilization. The electronic management system actively identified the unqualified sterilization process once. 224 batches of implant products including 1 106 bags were sterilized utilizing the electronic management system. 343 (31. 01%) bags were released early according to the fifth kinds of chemical indicative cards in the batch monitoring package, while the rest were released according to the biological monitoring results. Conclusions The electronic management system can improve the sterilization quality, reliability, and reduce the occult threat, by the control of the key parameters of pressure steam sterilization process and the process monitoring results.

The manifestations of current poor doctor -patient communication are: doctors have insufficient communication beforehand , randomness is big , communication is not detailed or in -depth , the patients also have certain shortcomings .The causes of this situation are: interests driven factors , lack of education supervision and management , service responsibility consciousness weakening .Therefore , should strengthen the propaganda and ed-ucation, raise awareness, constantly enhance the consciousness of doctor -patient communication; to strengthen the construction of medical ethics , to reconstruct the doctor -patient integrity , play up the solid foundation of doc-tor-patient communication;Strengthen supervision and management , establish and improve the system , to insure the good doctor-patient communication , orderly and transparent;reinforcement learning training , pay attention to the accumulation of human skills to develop and enhance the effectiveness of doctor -patient communication .