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.

Objective:To explore the diagnosis process and treatment experience of severe coronavirus disease 2019 (COVID-19) patients with heparin resistance (HR).Methods:The medical team of the First People's Hospital of Lianyungang admitted 2 severe COVID-19 patients with HR in intensive care unit (ICU) during their support to the designated hospital for the treatment of COVID-19 patients in Lianyungang City in November 2021. The clinical features, laboratory examinations, imaging features, treatment and prognosis of the two patients were analyzed.Results:Both severe COVID-19 patients received mechanical ventilation, 1 patient was treated with extracorporeal membrane oxygenation (ECMO) support. Both patients were complicated with lower extremity deep venous thrombosis and HR phenomenon under routine dose anticoagulant therapy. The maximum daily dose of unfractionated heparin exceeded 35 000 U (up to 43 200 U), the 2 patients failed to meet the standard of anticoagulation treatment, and the course of disease was prolonged. After that, argatroban was given 0.4 μg·kg -1·min -1 combined with anticoagulant therapy, the activated partial thromboplastin time (APTT) of patients undergoing ECMO could be maintained at 55-60 seconds and the activated coagulation time (ACT) of them could be maintained at 180-200 seconds. After ECMO support or later sequential mechanical ventilation, both patients recovered and were discharged, and deep venous thrombosis was also effectively controlled. Conclusion:HR phenomenon often occurs during the treatment of severe COVID-19 patients, the anticoagulation regimen should be adjusted in time, and the anticoagulation effect combined with argatroban is clear.

Objective To assess the influence on radiation dose and image quality of bronchial artery CT angiography for hemoptysis patients with high heart rate and free respiratory with single-cardiac dynamic volumetric scanning using 320-row CT.Methods During October 2016 and May 2017,totally 151 hemoptysis patients with heart rate ≥ 65 bmp and free-breathing were scanned for bronchial artery imaging with prospective ECG-gating 320-detector row dynamic volume CT.The patients were randomly divided into two groups,group A(81 cases) and group B(70 cases).Default multi-cardiac cycle scanning style was used for group A to generate multi-sector images A 1 which were reconstructed corresponding single-sector images A2.Single-cardiac periodic scanning was used to get single-sector images for group B.The effective doses (E) of two scanning types,the quantitative parameters of image quality [vascular CT value,image noise (SD),signal-to-noise ratio (SNR),contrast-to-noise ratio (CNR)] and subjective scoring of group B and A1,A2 were compared.The detection accuracy of the systemic artery-pulmonary circulation shunts was evaluated by ROC curve against digital subtraction angiography (DSA).The measurement data was analyzed by independent sample t test while the grade data was tested by independent sample nonparametric test.Results The median value of radiation dose in group B was significantly lower than that of group A (1.42 mSv vs.3.06 mSv,Z=-8.724,P＜0.05).There were no statistically significant differences in quantitative parameters and subjective scoring points of image quality between group B and group A2 (P＞ 0.05).The median subjective scoring points of group B was 4,which was better than that of group A1 (Z =-10.584,P＜ 0.05).The differences of SD,SNR,CNR betweengroup B and group A1 were statistically significant(t =-0.983,7.898,7.695,P＜0.05),and group B had higher SD,SNR and CNR.There was no significant difference in the mean CT values of the aorta and pulmonary artery between the two groups (P ＞ 0.05).The detection accuracy of the systemic arterypulmonary circulation shunts was moderately high in group B and group A2.The area under the ROC curve (AUC) was 0.891 and 0.864,respectively (Z=7.210,7.430,P＜0.05).The accuracy of group A1 was poor.The area under the ROC curve was 0.626 (Z=2.434,P＜0.05).The sensitivity of group B and groupA2 were 80％ and 76.2％,respectively (P＜0.05),and 28.6％ of group A1 (P＜0.05).Conclusions The 320-row single-cardiac periodic dynamic volume CT can effectively improve the image quality and the detection accuracy of the systemic-pulmonary circulation on CT,and reduce the radiation dose of the bronchial artery CT angiography.

Objective To study the relationship between hypertensive cerebral hemorrhage and microbleeds by analyzing the characteristics of magetic susceptibility-weighted imaging.Methods Fifty-one patients with mild hypertensive cerebral hemorrhage admitted to Shenzhen Nanshan District No.6 People's Hospital for MRI (T1WI,T2WI and T2FLAIR),susceptibility-weighted imaging,and magnetic resonance angiography from June 2016 to June 2017 were included in this study.Their MRI data were analyzed.Results Multiple foci of microbleeds and small vessel hyperplasia were detected in hemorrhage regions of the 51 patients included in this study,including ＞2 foci of microbleeds in intracranial basal area,thalamus,brain stem and cerebellar area of 40 patients (78.4％),and cerebral small vessel hyperplasia and VR space enlargement in 11 patients (21.6 ％).Magnetic resonance angiography showed cerebral middle artery and basal artery atheroclerosis in 15 patients but no vascular dissection,stenosis,aneurysm and vascular malformation in the other patients.Conclusion MRI can show the pathological changes in cerebral blood vessels of hypertensive hemorrhage patients,including cerebral microbleeds,cerebral small vessel hyperplasia and VR space enlargement.

Objective To discuss the influence of the change in ceiling-mounted shield positions on the radiation doses to the first and second operators during percutaneous coronary intervention.Methods In this study,the entrance surface dose (ESD) rates were measured for the first and second operators at 125 cm and 155 cm height on different ceiling-mounted shield positions separately through transradial approach.Measurements were repeated 20 times for each position and T test was used for statistical analysis of dose rate arithmetic mean values.Results For the first operator,the effective dose values were obtained only on left foot position.The ESD rate values at ceiling-mounted shield position close to patient were higher than that close to operators (t125 =46.9,t155 =4.1,P ＜0.05).For the second operator,the ESD rate values on his foot position,right foot position,left anterior oblique position and right anterior oblique position at ceiling-mounted shield position close to the operator,were higher than that close to the patient separately (t125 =11.9,24.4,11.2,2.7,t155 =16.1,2.8,14.4,28.8,P ＜ 0.05).The ESD rate values on head position,left foot position,left head position at ceiling-mounted shield position close to the operator,were lower than that close to the patient (t125 =-4.3,-2.4,-80.4,t155 =-10.2,-6.7,-152.6,P ＜ 0.05).Conclusions The change in the ceiling-mounted shield positions gave rise to change in radiation dose to the operators.The changes in radiation doses caused by the changes in ceiling-mounted shield positions are different in various angiographic positions.Ceiling-mounted shield should be used in a reasonable way in agreement with different positions in percutaneous coronary intervention so as to effectively reduce operators radiation dose.

Objective To analyze crossed cerebellar diaschisis(CCD) after subacute phase of spontaneous cerebral hemorrhage(SPSCH)and it's relevant factors with whole-brain CT perfusion(CTP) imaging. Methods Eighty-six patients diagnosed with unilateral SPSCH by CT were prospectively enrolled in our study from July 2015 to October 2016. Whole-brain CTP was performed in each patient.Cerebral blood flow(CBF), cerebral blood volume(CBV), mean transit time(MTT)and time-to-peak(TTP) inipsilateral and contralateral cerebellum were manually measured.The asymmetric indexs(AIs) were also calculated. Moreover, the volume of hematoma, the maximumarea of peri-hematomahypoperfusionin CBF and clinical factors(age, gender, time intervals from symptom onset)were analyzed,and NIHSS scores were used to evaluate the neurological status before patient admission, inspection, and discharge.CCD was rated positive when a unilateral supratentorial hematomawas appeared and an accompanying perfusion decrease was showed in the contralateral cerebellum on at least two sequential slices of CTP maps.All the individuals were divided into two groups including CCD-positive groupand CCD-negative group. The perfusion parameters (CBF, CBV, MTT, and TTP)between the contralateral and ipsilateral cerebellum were analyzed by the two-tailed paired t-test in CCD-positive group. The differences in the perfusion and clinical variables between the two groups were analyzed by the independent sample t-test and the Chi-squared test. Therelationships between the AI values and clinical or radiologic variables were assessed with Pearson correlation test. Results We found 35 CCD positive cases and 51 negative cases in the 86 patients.In CCD-positive groups, the perfusion values of cerebellumipsilateral and contralateral to the hematomawere as follows:CBF were (40.88±11.23) vs. (33.91±9.96) ml·100 g-1·min-1, CBV were (3.30±1.18) vs. (2.75±1.13) ml/100 g and TTP were (22.09±3.98) vs. (22.88±4.15) s, respectively, and there was statistical significance (t=10.231,8.223,-2.883,P<0.05).In CCD positive group, CBF, CBV, TTP, and MTT of the contralateral cerebellar hemisphere was changed in 35, 32, 26, and 16 cases,respectively.The AI value of CBF(AICBF)in CCD-positive group was (17.10±9.10)%, which was higher than that in the negative group (-0.95±17.01)%, there was statistical significance(t=6.367,P<0.05).The AI value of CBV(AICBV)was (17.43 ± 11.65)% in CCD-positive group, also significantly higher than that in negative group which was (1.55±21.06)%(t=4.477, P<0.05). No statistical difference(P>0.05)was found in hematoma location,hematoma volume, supratentorialhypoperfusion area and NIHSS scores(at admission, inspection)between CCD-positive and negative groups.The AICBF and AITTP showed linear correlation with time intervals in CCD-positive patients(P<0.05). Conclusions CCD is a common phenomenon in patients with SPSCH.Of all the perfusion parameters,CBF abnormalities are more common.The severity of CCD has a certain correlation with time intervals.There is no significant correlation between CCD and the clinical or radiological data(age, NIHSS scores,hematoma volume, and supratentorial hypoperfusion area).

OBJECTIVE:To optimize the purification technology of total alkaloid from the flos of Aconitum kusnezoffii. METH-ODS:The content of total alkaloid from the flos of A. kusnezoffii was determined by acid-base titration. The purification technology of total alkaloid from the flos of A. kusnezoffii was optimized by ion resin with resin type,mass concentration of loading liquid and exchange speed as factors,maximum adsorption quantity,desorption rate and mass fraction of total alkaloid as index,and verifica-tion test was conducted. RESULTS:The optimal purification technology was as follows as type 732 cation exchange resin,mass concentration of loading liquid 0.32 g/L,exchange speed of 7 column volume(BV)/h. In validation test,the content of total alka-loid was 86.88%(RSD=0.52%,n=3),and desorption rate was 92.81%(RSD=0.40%,n=3)averagely. The extraction trans-port rate of total alkaloid from 3 batches of the flos of A. kusnezoffii was 81.76% and purification transport rate was 89.47% in av-erage. CONCLUSIONS:The established method is stable and feasible,and shows high transport rate.

Objective To discuss the effect of the bedside shielding protection on the first and second operators against position radiation in percutaneous coronary intervention.Methods The surface entrance dosage rate for the first and second operators at 125 cm height with and without radiation protection shielding (provided separately) were measured.The t-test was used for statistical analysis of arithmetic mean values of dosage rates.And the effect of bedside shielding protection was calculated.Results The position radiation dosage rate at which the first operator exposed was significantly higher than that for the second in the case of no bedside protection (t =97.1-2 263.0,P ＜ 0.05),whereas the dosage rate at which the first operator (except for the left foot position) exposed was significantly lower than that for the second in the case of no bedside protection (t =-80.9-275.1,P ＜ 0.05).The shielding effect of bedside protection on the first and second operators was in the range of 92.26％-99.36％ and 27.83％-97.90％,respectively.Conclusions The bedside protection may effectively reduce position radiation dose to patients and the use of bedside protection changed the trends in the dose distribution in operators' standing region.Attention should be focused on the radiation protection of the second operators in daily work by making full use of bedside protection.

OBJECTIVETo investigate both genetic and environmental influences on the exercise participation and sedentary behavior in Qingdao, Shandong province and 326 in Lishui, Zhejiang province.

METHODS568 twin pairs, including 242 in Qingdao and 326 in Lishui, were studied. Exercise participation was measured by two questions on the frequency and intensity and then divided into two groups. Sedentary behavior was measured by one question as 'how long do you spend on sitting every day'. Variance component models based on twins was used to estimate the genetic and environmental factors on these traits.

RESULTSThe average age in monozygotic twins was (41.14 ± 10.11)while in dizygotic twins it was (41.23 ± 9.89). Genetic factors accounted 78% (35%-96%) and 59% (0-94%) for exercise participation variance in Qingdao and Lishui in people aged between 20 and 40. However, there were no heritability noticed on physical activity in people older than 40 years of age. Rates of heritability on sedentary behavior in Qingdao and Lishui were 68% (59%-75%) and 32% (7%-62%), respectively.

CONCLUSIONResults from the study suggested that sedentary behavior in Chinese people was influenced by genetic factors, which could also explain much of the exercise participation variance in people aged between 20 and 40.

Adult ; China ; Cross-Sectional Studies ; Exercise ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Sedentary Lifestyle ; Surveys and Questionnaires ; Twins ; genetics ; Young Adult

Objective To evaluate the feasibility of optimized scan protocol in whole-brain perfusion imaging with 320-MDCT scanner.Methods Twenty healthy volunteers were randomly divided into control group (13 patients) and test group (7 patients).The standard perfusion scan protocol (collecting 19 volumes)was applied in control group.The optimized perfusion CT scan protocol(collecting ll volumes)formulated by reducing scanning phases reasonably and changing the collection intervals was applied in test group.The regions of interest(ROI) with area of(20 ± 2)mm2 were located in the bilateral frontal white matter,parietal white matter,centrum semiovate,basal ganglia,occipital lobe and cerebellum.Bilateral perfusion values from ROI were measured,including cerebral blood volume(CBV),mean transit time (TTP),cerebral blood flow (CBF),mean transit time (MTT) and delay time (DT).Results Dose length product (DLP)and effective dose (ED)in optimized protocol were decreased 42.02％ as compared to control group.Every relative perfusion value of both sides from both groups were not statistically significant (P ＞ 0.05).Every relative perfusion parameters from individual territory in both groups showed no significant differences (P ＞ 0.05).Conclusions Using the optimized scan protocol,we could obtain the same whole-brain perfusion values could be obtained with the default standard protocol and less radiation dose.