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 incidence and mortality of breast cancer in tumor registration areas of Shanxi Province in 2019.Methods:A cross-sectional study was conducted. The tumor registration data reported by 13 tumor registration areas in Shanxi Province in 2019 were collected, and the overall incidence and mortality of breast cancer were analyzed. The stratified analysis was conducted by gender and region, and the incidence, mortality, accumulation rate (0-74 years old), age-specific incidence rate, age-specific mortality rate, Chinese population standardized rate and world population standardized rate were calculated. The standard population was based on the 2000 China population census standard population composition and Segi world standard population composition.Results:In 2019, there were 871 new cases of breast cancer in the tumor registration areas of Shanxi Province, with an incidence rate of 17.83/100 000, and 202 deaths, with a mortality rate of 4.13/100 000. The age-specific incidence of breast cancer was at a low level in 0-25 years old, it increased rapidly after 30 years old, and reached a peak in people aged 60 years old. The age-specific mortality showed a slow rising trend with the increase of age, and increased rapidly in people over 75 years old. The age-specific incidence and mortality of breast cancer in female were higher than those in male. Although the general trend of change concerning urban and rural age-specific incidence was similar, the trend of change concerning urban and rural age-specific mortality had their own characteristics. In 4 urban tumor registration areas, the highest male and female Chinese population standardized incidence rates were found in Yuci District of Jinzhong City (0.62/100 000) and Yangquan City (41.86/100 000). Male Chinese population standardized mortality rate was 0/100 000, and the highest female Chinese population standardized mortality rate was found in Yangquan City (12.62/100 000). In 9 rural tumor registration areas, the highest male and female Chinese population standardized incidence rates were found in Jishan County (2.59/100 000) and Pingding County (36.42/100 000). The highest Chinese population standardized mortality rates were found in Yuanqu County (0.89/100 000) and Jishan County (4.82/100 000).Conclusions:Women, urban area people and middle-aged and elderly people are the foci of breast cancer prevention and control in Shanxi Province.

Mild cognitive impairment (MCI) is the transitional stage between healthy aging and dementia, enjoying high risk of progression to Alzheimer's disease (AD). Therefore, MCI stage becomes the most important node for early identification, diagnosis and prevention of AD. At present, MCI clinical diagnosis lacks neuroimaging markers with non-invasive, timely and economic advantages. Recent studies suggest that microstructural and/or functional changes may occur in brain regions such as the hippocampus, amygdala, cingulate gyrus, thalamus, putamen, caudate nucleus and corpus callosum during MCI stage, and imaging features of these abnormal changes may serve as neuroimaging markers for early diagnosis of MCI. This article reviews the research progress on the abnormal changes of MCI related brain regions in neuroimaging.

Objective:To examine the mid - and long-term outcomes of surgical treatment of brachiocephalic Takayasu arteritis.Methods:This is a retrospective case series study. The clinical data of 39 patients,which had been diagnosed as brachiocephalic Takayasu arteritis (244 cases),who underwent surgical treatment,were analyzed between July 2012 to November 2022 at Department of Endoluminal Vascular Surgery, the First Affiliated Hospital of Zhengzhou University. There were 5 males and 34 females, aged (37.9±14.0)years (range:13 to 71 years). Despite medical treatment, the patients suffered severe ischemic symptoms continually and then underwent surgical interventions. Among them, 20 patients underwent endovascular procedures, 11 underwent open surgical procedures, and 8 underwent hybrid procedures. Patients were followed up through outpatient visits at 1, 3, 6 months after surgery and once every year later. Follow-up was conducted until November 2022. Operation status, postoperative complications and re-intervention of patients were recorded and the Kaplan-Meier survival curves were used to analyze postoperative vascular patency rates.Results:All 39 surgeries were successful, with no intraoperative death or serious complications. The follow-up period was (48.8±38.2) months(range:1 to 123 months). Thirty-three patients experienced symptom relief after surgery, and 6 patients required secondary surgical interventions. The patency rates for the endovascular treatment group at 1-, 3-, 5-, and 10-year were 95.0%, 75.2%, 60.2%, and 60.2%, respectively, while the patency rates for open surgery were all 90.9%. In the hybrid surgery group, the patency rates at 1-, 3-, 5-, and 8-year were all 87.5%.Conclusion:For patients with brachiocephalic Takayasu arteritis, choice of an appropriate blood flow revascularization intervention should be based on the patient′s condition,and the mid-and long-term outcomes are satisfactory.

Objective:To observe the short-and mid-term efficacy of left subclavian artery(LSA) laser in situ fenestration combined with arch debranching surgery for aortic arch reconstruction in patients with Stanford type A aortic dissection aged 60 years and above. Methods:This is a retrospective cohort study. A total of 41 Stanford type A aortic dissection patients aged 60 years and above who received combined surgery in Department of Endovascular Surgery, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were retrospectively analyzed. There were 25 males and 16 females, aged (67.3±5.9)years(range: 60 to 75 years). Among them, 19 patients underwent LSA laser in situ fenestration combined with arch debranching surgery(combined surgery group) and 22 patients underwent hybrid aortic arch debranching surgery(non-combined surgery group). Independent sample t test, χ2 test and Fisher exact probability method were used to compare the clinical characteristics of the two groups. Kaplan-Meier method was used for survival analysis, and the 5-year survival rate of the two groups was compared by Log-rank test. Results:Body mass index in the combined operation group was significantly higher than that in the non-combined operation group ((27.1±1.6)kg/m 2vs.(26.9±1.9)kg/m 2; t=2.766, P=0.006), and the difference was statistically significant. There was no statistical significance in the comparison of other general data (all P>0.05). The operation time ((321.3±11.4) minutes vs. (329.6±7.3)minutes; t=-2.733, P=0.010) and LSA reconstruction time ((32.4±3.0)minutes vs. (42.4±6.0)minutes; t=-6.842, P<0.01) in the combined operation group were significantly shortened, and the difference was statistically significant. The rate of LSA reconstruction in the combined operation group (100% vs. 72.7%; P=0.023) was significantly higher than that in the non-combined operation group, and the difference was statistically significant. There were no significant differences in the incidence of pulmonary infection, unplanned second operation, continuous renal replacement therapy, neurological complications and the in-hospital mortality between the two groups. Compared with the non-combined surgery group, the total complication rate related to LSA reconstruction was significantly lower in the combined surgery group (0 vs. 27.3%; P=0.023). Kaplan-Meier survival analysis showed that there was no difference in 5-year survival rate between the combined operation group and the non-combined operation group (84.2% vs. 77.3%; χ2=0.310, P=0.578). Conclusion:Laser in situ fenestration of the LSA combined with arch debranching surgery to reconstruct the aortic arch can significantly shorten the operation and LSA reconstruction time in patients aged 60 years and above with Stanford type A aortic dissection, improve the success rate of LSA reconstruction, and reduce the occurrence rate of LSA reconstruction complications.

Objective:To examine the mid - and long-term outcomes of surgical treatment of brachiocephalic Takayasu arteritis.Methods:This is a retrospective case series study. The clinical data of 39 patients,which had been diagnosed as brachiocephalic Takayasu arteritis (244 cases),who underwent surgical treatment,were analyzed between July 2012 to November 2022 at Department of Endoluminal Vascular Surgery, the First Affiliated Hospital of Zhengzhou University. There were 5 males and 34 females, aged (37.9±14.0)years (range:13 to 71 years). Despite medical treatment, the patients suffered severe ischemic symptoms continually and then underwent surgical interventions. Among them, 20 patients underwent endovascular procedures, 11 underwent open surgical procedures, and 8 underwent hybrid procedures. Patients were followed up through outpatient visits at 1, 3, 6 months after surgery and once every year later. Follow-up was conducted until November 2022. Operation status, postoperative complications and re-intervention of patients were recorded and the Kaplan-Meier survival curves were used to analyze postoperative vascular patency rates.Results:All 39 surgeries were successful, with no intraoperative death or serious complications. The follow-up period was (48.8±38.2) months(range:1 to 123 months). Thirty-three patients experienced symptom relief after surgery, and 6 patients required secondary surgical interventions. The patency rates for the endovascular treatment group at 1-, 3-, 5-, and 10-year were 95.0%, 75.2%, 60.2%, and 60.2%, respectively, while the patency rates for open surgery were all 90.9%. In the hybrid surgery group, the patency rates at 1-, 3-, 5-, and 8-year were all 87.5%.Conclusion:For patients with brachiocephalic Takayasu arteritis, choice of an appropriate blood flow revascularization intervention should be based on the patient′s condition,and the mid-and long-term outcomes are satisfactory.

Objective:To observe the short-and mid-term efficacy of left subclavian artery(LSA) laser in situ fenestration combined with arch debranching surgery for aortic arch reconstruction in patients with Stanford type A aortic dissection aged 60 years and above. Methods:This is a retrospective cohort study. A total of 41 Stanford type A aortic dissection patients aged 60 years and above who received combined surgery in Department of Endovascular Surgery, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were retrospectively analyzed. There were 25 males and 16 females, aged (67.3±5.9)years(range: 60 to 75 years). Among them, 19 patients underwent LSA laser in situ fenestration combined with arch debranching surgery(combined surgery group) and 22 patients underwent hybrid aortic arch debranching surgery(non-combined surgery group). Independent sample t test, χ2 test and Fisher exact probability method were used to compare the clinical characteristics of the two groups. Kaplan-Meier method was used for survival analysis, and the 5-year survival rate of the two groups was compared by Log-rank test. Results:Body mass index in the combined operation group was significantly higher than that in the non-combined operation group ((27.1±1.6)kg/m 2vs.(26.9±1.9)kg/m 2; t=2.766, P=0.006), and the difference was statistically significant. There was no statistical significance in the comparison of other general data (all P>0.05). The operation time ((321.3±11.4) minutes vs. (329.6±7.3)minutes; t=-2.733, P=0.010) and LSA reconstruction time ((32.4±3.0)minutes vs. (42.4±6.0)minutes; t=-6.842, P<0.01) in the combined operation group were significantly shortened, and the difference was statistically significant. The rate of LSA reconstruction in the combined operation group (100% vs. 72.7%; P=0.023) was significantly higher than that in the non-combined operation group, and the difference was statistically significant. There were no significant differences in the incidence of pulmonary infection, unplanned second operation, continuous renal replacement therapy, neurological complications and the in-hospital mortality between the two groups. Compared with the non-combined surgery group, the total complication rate related to LSA reconstruction was significantly lower in the combined surgery group (0 vs. 27.3%; P=0.023). Kaplan-Meier survival analysis showed that there was no difference in 5-year survival rate between the combined operation group and the non-combined operation group (84.2% vs. 77.3%; χ2=0.310, P=0.578). Conclusion:Laser in situ fenestration of the LSA combined with arch debranching surgery to reconstruct the aortic arch can significantly shorten the operation and LSA reconstruction time in patients aged 60 years and above with Stanford type A aortic dissection, improve the success rate of LSA reconstruction, and reduce the occurrence rate of LSA reconstruction complications.

Objective:To analyze the clinical characteristics and treatment of patients with renovascular hypertension (RVH) caused by renal arterial fibromuscular dysplasia (FMD).Methods:Clinical data and treatment result of 38 patients with renal arterial FMD and RVH admitted to our hospital from Jan 2014 to Dec 2020 were reviewed.Results:A total of 38 patients were enrolled in this study. Renal artery CTA showed that 40 renal arteries were involved, among these 6 branches had multifocal stenosis, and 34 branches had focal stenosis. Thity-three patients received surgical treatment, of which 32 patients underwent percutaneous transluminal renal angioplasty (PTRA), and 1 patient with renal aneurysm underwent renal artery stent implantation combined with aneurysm coil embolization. Postoperative blood pressure was significantly lower than that before the operation [(129.79±17.63) mmHg vs. (178.52±28.63) mmHg, t=-11.42, P<0.001]. The mean follow-up time was 35.5 months. Renal artery restenosis occurred in 4 patients and underwent reintervention. Conclusion:For patients with renal arterial FMD and RVH, PTRA is safe and effective, especially for patients with focal lesions, with fair short and mid-term prognosis.

Objective:To evaluate the mid-term results of endovascular treatment for transplant renal artery stenosis (TRAS).Methods:The clinical and follow-up data of TRAS patients undergoing endovascular treatment at the First Affiliated Hospital of Zhengzhou University from Jan 2014 to Jan 2021 were retrospectively analyzed.Results:A total of 2 230 patients underwent kidney transplantation, 78 cases(3.6%) developed TRAS, among those 27 patients received endovascular treatment and followed-up from 12 to 80 months(mean 36 months). Thirteen patients (48.1%) underwent renal graft angiography and balloon dilatation, of which 2 patients underwent stent placement, 14 patients (51.9%) underwent renal graft angiography with balloon dilatation and stenting. The serum creatinine 2 weeks postoperatively and 12 months postoperatively were 127.6 μmol/L (47-220 μmol/L) and 103.4 μmol/L (63-166 μmol/L), respectively, significantly lower than the preoperative 217.1 μmol/L (98-541 μmol/L), ( P<0.05). Glomerular filtration rate (GFR) before surgery was 8.3-105.3 ml/min, 2 weeks and 12 months after surgery compared to 24.6-132.2 ml/min and 47.3-113.9 ml/min( P<0.05). The preoperative peak systolic velocity (PSV) of the transplanted renal artery during the systolic phase was 234 cm/s (75-457 cm/s), compared to 129 cm/s (52-290 cm/s) ( P<0.05) 2 weeks and 118 cm/s (57-300 cm/s) 12 months postoperatively ( P<0.05). During the follow-up period, 2 patients (7.4%) died of multiple organ failure. Conclusions:TRAS is the most common vascular complication after kidney transplantation. Endovascular treatment has a high success rate and low complication rate.

Objective:To investigate the incidence and mortality of lung cancer in the cancer registration areas of Shanxi Province in 2017.Methods:The cancer registration data reported by 12 tumor registration areas of Shanxi in 2017 were sorted out and stratified by urban and rural areas and gender. The number of incidence and death ,the crude incidence and mortality, the cumulative rate (0-74 years), age-specific incidence and mortality, Chinese population standardized rate and world population standardized rate were calculated. The incidence and mortality were standardized by the 2000 China census standard population composition and Segi's world standard population composition.Results:In 2017, there were 2 275 new cases and 1 736 deaths of lung cancer in the tumor registration area of Shanxi Province. The crude incidence rate of lung cancer was 46.72/100 000 (male 63.99/100 000, female 28.80/100 000, urban area 58.05/100 000, rural area 39.09/100 000), Chinese population standardized rate was 31.67/100 000, the world population standardized rate was 32.10/100 000, and the cumulative rate (0-74 years) was 3.87/100 000. The crude mortality rate was 35.65/100,000 (male 49.84/100,000, female 20.93/100,000, urban area 44.53/100,000, rural area 29.67/100 000), Chinese population standardized rate was 23.82/100 000, the world population standardized rate was 24.14/100 000, and the cumulative rate (0-74 years) was 2.69/100,000. Overall, the age-specific incidence and mortality of lung cancer in 2017 were at a low level in 0-44 years age group, and increased rapidly after 45 years age group, and reached a peak in 85 years age group. The incidence and mortality of lung cancer in males were higher than that in females. Although there were some differences in the incidence and mortality of patients with different ago range in urban and rural areas, the overall trend was similar.Conclusions:Lung cancer is the most common malignant tumor threatening the health of residents in Shanxi Province. Male, urban areas and middle-aged and elderly population are the focus of cancer prevention and control in Shanxi Province. Lung cancer prevention and control should be targeted carried out according to the differences between urban and rural areas and gender.