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 investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Buxrugulosides A-E, four lignan glycosides (1-4) and a protocatechuate derivative (5) featuring a rare (N, N-diethyl)methyl amino group at aromatic rings, were obtained from the aerial parts of Buxus rugulosa, which is famous for treating coronary heart disease. Their structures including absolute configurations were elucidated by HRMS, 1D and 2D NMR, and by comparing their CD data with previous reports. Compound 1 was a rare sesquilignan, and all of these compounds were the first example of lignans with (N, N-diethyl)methyl amino group.

OBJECTIVE: To estimate the biological dose by the chromosome aberration analysis in a victim suffered in the radioactive source-loss accident in Nanjing City. METHODS: Peripheral blood sample of the victim was collected 6 days after radioactive exposure. Individual radioactive biological dose was estimated by identifying the aberration of the dicentrics plus centric rings in the metaphase chromosome of cells. The distribution of chromosome aberration was tested by the Poisson distribution. Impure Poisson distribution was used to estimate the radiation dose. RESULTS: Among the 353 cells observed at metaphase,75 aberration of dicentrics plus centric rings were found,43 cells had 1 aberration and 7 cells had 2 aberrations. Moreover,there were 3 multi-aberration cells with 3,4 and 11 aberrations respectively. The average individual radiation dose was estimated to be 1. 52 Gy,which was consistent with the clinical diagnosis as mild acute bone marrow radiation disease. The Poisson distribution u test revealed that the patient suffered from nonhomogeneous radiation.By the impure Poisson distribution test,the radiation exposure proportion of the whole body was estimated to be 55% and the average dose was 3. 02 Gy. CONCLUSION: The biological dose estimation was successfully performed,the results showed that this was a case of nonhomogeneous irradiation.

OBJECTIVETo introduce the imaging characteristics of moyamoya disease (MMD) using high-resolution magnetic resonance imaging (HR-MRI) and to discuss the role of HR-MRI in differentiating MMD from other intracranial artery diseases, especially intracranial atherosclerotic disease (ICAD).

DATA SOURCESThis review was based on the data in articles published between 2005 and 2015, which were obtained from PubMed. The keywords included HR-MRI, MMD, ICAD, and intracranial artery diseases.

STUDY SELECTIONArticles related to HR-MRI for MMD or other intracranial artery diseases were selected for review.

RESULTSThere are differences between the characteristic patterns of HR-MRI in MMD and ICAD. MMD is associated with inward remodeling, smaller outer diameters, concentric occlusive lesions and homogeneous signal intensity, while ICAD is more likely to be associated with outward remodeling, normal outer diameters, eccentric occlusive lesions, and heterogeneous signal intensity. Other intracranial artery diseases, such as dissection and vasculitis, also have distinctive characteristics in HR-MRI. HR-MRI may become a useful tool for the differential diagnosis of MMD in the future.

CONCLUSIONSHR-MRI of MMD provides a more in-depth understanding of MMD, and it is helpful in evaluating pathological changes in the vessel wall and in differentiating MMD from other intracranial artery steno-occlusive diseases, particularly ICAD.

Objective To investigate the significance of monitoring P(c-a)CO2 (the gradients between transcutaneous PCO2 and arterial PCO2) in patients with septic shock.Method 31 patients with early septic shock were enrolled as the study group and 20 patients with stable hemodynamics as the control group from Fab.2013 to Sept.2014 in our Intensive Care Unit (ICU).The patients with septic shock were treated guided by early goal directed therapy (EGDT) within 6 hours since hospitalization.The differences of baseline P(c-a) CO2 levels and other index as arterial lactate (LAC) concentration between two groups and the variations of these indexes after EGDT in the study group were compared respectively.Results The baseline levels of P(c-a)CO2 and LAC in patients with septic shock were significantly higher than in patients of control group: (21.2 ± 10.1) mmHg vs.(7.5 ±4.6), P =0.000, and (4.0±2.4) mmol/ Lvs.(1.6 ± 0.5), P =0.000.The areas under receiver operator characteristic (ROC) curve (AUC) for baselineP(c-a)CO2 and LAC were 0.918 (95％ CI: 0.843-0.992) and 0.840 (95％ CI: 0.719-0.962) respectively.A threshold of 14.0 mmHg for P(c-a)CO2 and 2.1 mmol/L for LAC discriminated patients with septic shock from without shock with the same sensibility of 83.9％ and the same specificity of 90.0％, respectively.With regard to prognosis (Day 28), AUC for baseline P(c-a)CO2 and LAC were 0.739 (95％ CI: 0.562-0.917) and0.702 (95％ CI: 0.514-0.889) respectively.A threshold of 21.5 mmHg for P(c-a) CO2 and 3.9 mmol/L for LAC discriminated survivors from nonsurvivors with the same sensibility of 71.4％ and the same specificity of 70.6％ respectively.31 patients in the study group completed EGDT within 6 hours after the admission, 16 (51.6％) passed EGDT and 13 (81.3％) survived, 15 (48.4％) failed EGDT and 4 (26.7％) survived, and survival rates were significantly different, F =9.314, P =0.004.After EGDT, P(c-a) CO2 (18.8 ± 9.4) mmHg and LAC (3.3 ± 2.4) mmol/Lreduced significantly compared with the baselines, all P =0.000.AUC then for P(c-a) CO2 and LAC were 0.742 (95％ CI: 0.562-0.921) and 0.769 (95％ CI: 0.593-0.945), respectively.A threshold of 18.3 mmHg for P(c-a)CO2 and 3.1 mmol/L for LAC discriminated survivors from nonsurvivors with the same sensibility of 71.4％ and the specificity of 71.4％ and of 76.5％ respectively.P(c-a) CO2 and LAC of patients passed EGDT reduced significantly compared with those failed EGDT: (14.8 ± 7.5) mmHgvs.(23.6±9.6) mmHg (P=0.012)、 (2.5±1.5) mmol/L vs.(4.3±2.9) mmol/L (P=0.038), and so did with their baseline : (14.8±7.5) mmHgvs.(18.0±8.1) mmHg, (P=0.042)、 (2.5±1.5) mmol/Lvs.(3.2±1.8) mmol/L, P=0.043.In patients failed EGDT, P(c-a)CO2 and LAC changed little after EGDT, from (24.6 ± 9.2) to (23.6 ± 9.6) mmHg (P =0.238) and from (4.8 ± 2.5) mmol/L to (4.3 ± 2.9) mmol/L (P =0.629).When baseline levels were compared between patients passed EGDT with those failed EGDT, P(c-a) CO2 was (18.0 ±8.1) mmHg vs.(24.6 ± 9.2) mmHg (P =0.042), LAC was (3.2 ± 1.8) mmol/L vs.(4.8 ± 2.5) mmol/L (P =0.050).Conclusions P(c-a) CO2 ＞ 14.0 mmHg could play a role in recognizing early septic shock.EGDT was an effective therapy for the disease and P(c-a)CO2 level could reflect the efficacy of EGDT.P(c-a)CO2 ＞ 21.5mmHg before EGDT and P(c-a) CO2 ＞ 19.3 mmHg after EGDT both could predict the prognosis of patients with septic shock.All above correlated well with LAC and represented a new efficient technique to assess tissue microperfusion.

Objective To evaluate the prevalence of depression,anxiety and suicide behavior in patients suffering from tuberculosis in Hangzhou and to explore their relationship with medication adherence. Methods Demographic characteristics,self-rating anxiety scale (SAS),the center for epidemiological studies -depression (CESD),social support rating scale (SSRS),suicide behavior information and the morisky medication adherence scale (MMAS)were investigated in 973 tuberculosis patients who were selected by systematic random sampling.Results The means of SAS and CESD were 39.71 ±8.30 and 14.16 ±10.77 respectively,which were both higher than the norms(P<0.01).Totally 102 (10.48%)patients had anxiety and 333 (34.22%)were depressed.Out of 973 patients,60 (6.17%)reported suicide ideation after tuberculosis diagnosis.The prevalence of non -adherence was 20.55%,which was defined with MMAS score above one and more.The non -adherence group had higher anxiety,depression and suicide ideation prevalence than the adherence group (15.50%vs.9.18%,46.50%vs.30.66%,11.00%vs.4.92%respectively,P<0.01).The mean score of SSRS,subjective support,objective support and utilization of support in the non-adherence group were 30.71 ±5.15,4.61 ±2.07,19.74 ±4.55 and 6.34 ±1.93 respectively,which were 34.06 ±7.39,6.62 ± 2.27,20.67 ±5.27 and 6.77 ±2.23 in the adherence group respectively.SSRS and its three dimension scores were significantly lower in the non-adherence group than that in the adherence group (P<0.01).Conclusion These findings show a quite serious situation of psychological problems of tuberculosis patients in Hangzhou and suggest psychological intervention should be included in adherence intervention.