Objective:To investigate the relationship between 21-gene recurrence risk score (21-Gene RS) and the prognosis and clinicopathological features of hormone receptor (HR) positive, HER2-negative early breast cancer patients who did not receive neoadjuvant therapy.Methods:A total of 469 patients with HR positive and HER2-negative early breast cancer who received surgical treatment in the First Affiliated Hospital, Zhejiang University School of Medicine from January 2014 to October 2017 were selected. Their clinicopathological data were retrospectively analyzed. Tumor tissue samples were collected from patients, and the expression of 21-gene was detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The 21-Gene RS was calculated according to the Trial Assigning Individualized Options for Treatment (TAILORx) RS grouping and National Surgical Adjuvant Breast and Bowel Project B-20 (NSABP B-20) RS grouping principles. Patients were divided into low (21-Gene RS<11 or 21-Gene RS<18), intermediate (11≤21-Gene RS<26 or 18≤21-Gene RS<31) and high (21-Gene RS≥26 or 21-Gene RS≥31) risk groups, and the clinicopathological features and prognostic differences of patients in different risk groups were compared. Statistical data were compared by chi-square test. Survival analysis was performed using Kaplan-Meier curve analysis and the differences between groups were compared using Log-rank test. Multivariate analysis was conducted by COX regression analysis.Results:Based on TAILORx RS grouping, the proportions of low-risk, intermediate-risk and high-risk groups among the 469 patients were 18.8% (88/469), 48.2% (226/469) and 33.0% (155/469), respectively. Based on NSABP B-20 RS grouping, the proportion of low-risk, intermediate-risk and high-risk groups were 43.1% (202/469), 37.5% (176/469) and 19.4% (91/469), respectively. The association of 21-Gene RS with histological grading, luminal typing, Ki-67 expression, and chemotherapy and treatment modalities were statistically significant ( P<0.05) regardless of TAILORx RS grouping or NSABP B-20 RS grouping. Kaplan-Meier survival curve suggested poor prognosis in high-risk group ( P<0.05, Log-rank test). Multivariate COX regression analysis showed that surgical method and 21-Gene RS were risk factors affecting the prognosis of patients. Conclusions:21-Gene RS is significantly associated with the prognosis of patients with HR-positive, HER2-negative, early-stage breast cancer not receiving neoadjuvant therapy, as well as with their clinicopathological characteristics such as patients′ histologic grade, luminal typing, Ki-67 expression, and whether or not they are treated with chemotherapy or other treatment modalities.The 21-Gene RS threshold of 11 and 26 or 18 and 31 can be used to grade the prognosis in Chinese patients with early-stage breast cancer. More researches are needed to guide the selection of postoperative adjuvant therapy for patients with HR-positive and HER2-negative early-stage breast cancer.

Objective:The DNA aptamers of lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker of vasculitis, were screened and a visual detection method using unlabeled nucleic acid aptamer-gold nanoparticle (AuNP) probe was established.Method:Lp-PLA2 aptamers were screened through 8 cycles of incubation binding, ssDNA isolation, PCR amplification and single strand recovery by the magnetic bead fixation SELEX technique. The affinity and specificity of the aptamers were validated using surface plasmon resonance technology and flow cytometry, and the secondary structure of the aptamer and its three-dimensional molecular docking with the target protein were simulated by computer software. Subsequently, aptamer-AuNP complex was prepared, and the color change was caused by salt-induced condensation of the AuNP solution by target competitive binding. Then, the target concentration was detected by measuring the absorbance of the solution with a spectrophotometer. The linear relationship between the sample absorbance and concentration of Lp-PLA2 were established under the optimal determine conditions.Results:Three Lp-PLA2 aptamers B76-2, B76-4 and B76-5 with high affinity and strong specificity were obtained, and the dissociation constants were 1.07, 1.26 and 1.75 nmol/L, respectively. Then AuNP colorimetric sensing method based on B76-2 aptamer was successfully constructed. The linear range and detection limit of Lp-PLA2 were 20-500 ng/ml and 78 ng/ml, respectively, and the reaction time was 30 min, which could specifically distinguish the target from other thrombotic markers such as thrombin and myeloperoxidase.Conclusion:A simple, rapid and specific visual detection method for visually detecting Lp-PLA2 was established by using aptamer-AuNP colorimetric assay.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.

Objective To investigate the effect of gaseous effluent from the six generator sets on the radiation level of the surrounding terrestrial environment in Daya Bay Nuclear Power Base after the operation of Ling’ao Nuclear Power plant. Methods The radiation level in the peripheral environment of the Base was monitored using the thermoluminescence dosimeter （TLD）. Twenty-five monitoring sites were set around the Base to investigate the variation of radiation level over a long period of time by collecting the TLDs every three months. Results From 2011 to 2020, the annual γ dose rate of the 25 sites ranged from 76.7 to 207.1 nGy/h, with an average value of (123.3 ± 5.7) nGy/h and a relative deviation of 2%-12%. The TLD monitoring and instantaneous measuring results of γ dose rate were consistent with the survey of the State Environmental Protection Administration in the 20th century and the baseline level prior to the operation of the nuclear power plant. Conclusion There are great differences in natural environmental radiation level across the TLD monitoring sites. The overall environmental γ radiation level within 50 km of the nuclear power base remains unchanged. The emission of gaseous effluent from the operation of the nuclear power plant does not have a cumulative impact on the radiation level of surrounding environment.

Objective:To study the correlation between liver imaging reporting and data system (LI-RADS) category with tumor differentiation, Ki67 index, microvascular infiltration, and predictive prognosis in hepatocellular carcinoma (HCC).Methods:We retrospectively analyzed the clinical and radiological data of 178 patients with HCC who were confirmed by histopathological studies after liver resection between January 2015 and September 2020 at Lishui Central Hospital and Lishui People’s Hospital. There were 156 males and 22 females, with age of (57±10) years old. These patients were assessed for LI-RADS categories according to the 2018 version of LI-RADS, and they were divided into 4 groups according to the assessment results: 12 patients with LI-RADS-3 (the LI-RADS-3 group); 26 patients with LI-RADS-4 (the LI-RADS-4 group); 102 patients with LI-RADS-5 (the LI-RADS-5 group); and 38 patients with LI-RADS-M (the LI-RADS-M group). The patients' general information, tumor markers, pathology and other clinical data were recorded. Correlation analysis between the LI-RADS category with pathology was performed by the Kendall's tau-b test. Survival analysis between groups was performed by the Kaplan-Meier analysis. The Cox regression risk model was used to analyze the relationship between these variables with the risk of death.Results:The Kendall's tau-b test showed that LI-RADS category was positively correlated with the degree of tumor differentiation ( t=0.204, P=0.002), but not with microvascular infiltration and Ki 67 index ( P>0.05). All patients were followed up for 4.2 to 84.2 months (median follow-up 36.3 months). By the end of follow-up, 31 patients had died and 147 patients were alive. The cumulative 1-year and 3-year survival rates of the LI-RADS-5 group were 97% and 90% respectively, which were significantly higher than those in the LI-RADS-M group (81% and 63%), and the LI-RADS-4 group (96% and 81%), ( P<0.05). The cumulative 1-year and 3-year survival rates of patients in the LI-RADS-3 group were 100% and 67% respectively, and there was no statistically significant difference with the LI-RADS-5 group ( P>0.05). The Cox multivariate regression analysis showed that tumor glycoantigen 199 (>50 μl/ml) to be an independent influencing factor in survival of HCC patients ( HR=0.43, 95% CI: 0.24-0.76, P=0.004). Conclusion:The LI-RADS category of HCC was positively correlated with the degree of tumor differentiation, and patients with HCC meeting the LI-RADS-5 criteria had relatively better prognosis.

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical morbidity. Enterolysis at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary adhesion. Here we studied the preventive effects of different approaches of berberine treatment for primary adhesion, and its effects on adhesion reformation compared to Interceed. We found the primary adhesion was remarkably prevented by berberine through intraperitoneal injection 30 min before abrasive surgery (pre-berberine) or direct addition into injured cecum immediately after the surgery (inter-berberine). Rats with adhesion reformation had a more deteriorative collagen accumulation and tissue injury in abrasive sites than rats with primary adhesion. The dysregulated TIMP-1/MMP balance was observed in patients after surgery, as well as adhesion tissues from primary adhesion or adhesion reformation rats. Inter-berberine treatment had a better effect for adhesion reformation prevention than Interceed. Berberine promoted the activation of MMP-3 and MMP-8 by directly blocking TIMP-1 activation core, which was reversed by TIMP-1 overexpression in fibroblasts. In conclusion, this study suggests berberine as a reasonable approach for preventing primary adhesion formation and adhesion reformation.

Objective To compare the image quality produced by MR high resolution vessel wall imaging (HR?VWI) and ultrasound (US) in evaluating carotid plaque load. Methods This prospective study enrolled 21 patients with carotid plaques undergoing HR?VWI and subsequent 2D US between August 2016 to January 2017 in Hebei General Hospitial. The plaque thickness (PT), lumen area (LA), wall area (WA) and total vessel area (TVA) of the plaques were measured and normalized wall index (NWI) was calculated on both HR?VWI images and US for those plaques with image quality score≥3 and matching between the two methods. The plaque load index was compared by using the independent sample t test or the non?parametric Wilcoxon test, and the correlation between the indexes was based on the Pearson test. Results Forty?five carotid plaques were matched with HR?VWI and US. There was no significant difference in PT, LA, WA, TVA and NWI detected by HR?VWI and ultrasound (P>0.05). The parameters measured by two methods were correlated (r values were 0.83, 0.85, 0.32, 0.83 and 0.59, P<0.05). Conclusion There is a good consistency between HR?VWI and conventional ultrasound in the measurement of carotid plaque load.

OBJECTIVE:To improve the rational and scientific drug purchase quantity planned by hospital pharmacy. METH-ODS:The deficiency in present drug purchase module of hospital information system(HIS)was analyzed;the formula of planned purchase quantity was improved by incremental coefficient method,ABC analysis method and VEN analysis method. The high and low stored values and packaging volume were set to adjust planned drug purchase quantity. Based on the computer program,a one-key-getting procedure was quasi established,and five typical drugs were selected for simulation. RESULTS:Based on previous formula,the parameters representing change trend,incremental coefficient k1 and inventory coefficient k2 were added in new formu-la. The one-key-getting procedure could calculate the quantity of all drugs by simply entering the planning cycle N1 and the safe peri-od N2 of the some category drugs into the system. After simulated operation practice,compared with pre-improvement,the occupa-tion of funds was significantly decreased and the quantity of drug was rounded off according to package in post-improvement. CON-CLUSIONS:Through function improvement of drug purchase module in HIS and the quasi establishment of one-key-getting pur-chase mode,planned drug purchase quantity is more reasonable,scientific and accurate. It ensures the clinical drug supply in time without causing a backlog,and effectively reduces the cost of manpower,material and capital.

OBJECTIVETo investigate the association between children's and their parents' lifestyles, household environmental exposures and risk of childhood acute leukemia (AL).

METHODSA 1:2 matched case-control study of childhood AL was conducted in Shanghai between April 2011 and January 2014. The study enrolled 66 cases aged < 15, diagnosed with AL and 132 controls matched by age, gender and residence. All of the controls had no hematological diseases or previous history of malignancy. Children who had been adopted and had congenital genetic syndromes such as Down's syndrome or a positive HIV test result were not eligible as either cases or controls. Information was obtained from standardized face-to-face interviews of their parents/guardians with detailed questions on demographic characteristics, lifestyle, and household environment. Conditional logistic regression models were used to analyze effecting factors of childhood AL, odds ratios (OR) and their 95% confidence intervals (CI) were calculated.

RESULTSAmong 198 cases, 66 cases were aged (5.0 ± 3.7) years old, and 132 controls were aged (6.0 ± 3.8) years old (t = 0.48, P = 0.523). The paternal drink frequencies of cases and controls were 57.6% (38/66), and 31.1% (41/132), respectively (χ² = 4.91, P = 0.027). And the frequencies of household insecticides usage in the last year in the two groups were 78.8% (52/66), and 65.2% (86/132) (χ² = 3.87, P = 0.049). Chemical exposure during childhood (OR = 4.76, 95% CI: 1.34-16.89), maternal exposure to chemicals (OR = 4.51, 95% CI: 1.65-12.33), household insecticides use during 0-3 years of child (OR = 2.90, 95% CI: 1.31-6.39), and renovating after their children's birth (OR = 3.12, 95% CI: 1.26-7.74) were associated with an increased risk of childhood AL and these differences between the cases and the controls have statistical significance. Besides, we found that frequent contaction with other children during 0-3 years old (OR = 0.32, 95% CI: 0.15-0.69) and ventilation during sleeping in summer (OR = 0.43, 95% CI: 0.18-0.98) were associated with a decreased risk of childhood AL.

CONCLUSIONOur results support the association between children's and their parents' lifestyles, household environmental exposures and childhood AL.

Acute Disease ; Case-Control Studies ; Child ; Child, Preschool ; China ; Environmental Exposure ; Female ; Humans ; Insecticides ; Leukemia ; epidemiology ; Life Style ; Logistic Models ; Maternal Exposure ; Neoplasms ; Odds Ratio ; Parents ; Risk Factors

Objective To investigate the association between children's and their parents' lifestyles, household environmental exposures and risk of childhood acute leukemia (AL) . Methods A 1∶2 matched case-control study of childhood AL was conducted in Shanghai between April 2011 and January 2014. The study enrolled 66 cases aged<15, diagnosed with AL and 132 controls matched by age, gender and residence. All of the controls had no hematological diseases or previous history of malignancy. Children who had been adopted and had congenital genetic syndromes such as Down's syndrome or a positive HIV test result were not eligible as either cases or controls. Information was obtained from standardized face-to-face interviews of their parents/guardians with detailed questions on demographic characteristics, lifestyle, and household environment. Conditional logistic regression models were used to analyze effecting factors of childhood AL, odds ratios (OR) and their 95%confidence intervals (CI) were calculated . Results Among 198 cases, 66 cases were aged (5.0±3.7) years old, and 132 controls were aged (6.0±3.8)years old (t=0.48, P=
0.523). The paternal drink frequencies of cases and controls were 57.6% (38/66), and 31.1% (41/132), respectively (χ2=4.91, P=0.027). And the frequencies of household insecticides usage in the last year in the two groups were 78.8% (52/66), and 65.2% (86/132) (χ2=3.87, P=0.049). Chemical exposure during childhood (OR=4.76, 95%CI:1.34-16.89), maternal exposure to chemicals (OR=4.51, 95%CI:1.65-12.33), household insecticides use during 0-3 years of child (OR=2.90, 95%CI: 1.31-6.39), and renovating after their children's birth (OR=3.12, 95%CI:1.26-7.74) were associated with an increased risk of childhood AL and these differences between the cases and the controls have statistical significance. Besides, we found that frequent contaction with other children during 0-3 years old (OR=0.32, 95%CI:0.15-0.69) and ventilation during sleeping in summer (OR=0.43, 95%CI:0.18-0.98) were associated with a decreased risk of childhood AL. Conclusion Our results support the association between children's and their parents' lifestyles, household environmental exposures and childhood AL.