Objective To construct the small interfering RNA (siRNA) eukaryotic expression vector specific to human MGMT gene(pRNATin-H1.2/Neo MGMT siRNA) to observe its silencing effect on MGMT gene in vitro.Methods The pRNATin-H1.2/Neo MGMT siRNA expression vector was constructed by gene recombination,then transfected into the cultured HelaS3 cells.Inhibitory effect of siRNAs was detected by semi-quantitative RT-PCR.Results The pRNATin-H1.2/Neo MGMT siRNA expression vector was successfully constructed.Cells transfected with pRNATin-H1.2/Neo MGMT siRNA could obviously inhibit the expression level of MGMT gene.Conclusion The pRNATin-H1.2/Neo MGMT siRNA expression vector could inhibit the MGMT gene expression.

P21 (CDKN1A), a key cell cycle regulatory protein that governs cell cycle progression from G1 to S phase, can regulate cell proliferation, growth arrest, and apoptosis. The Ser31Arg polymorphism is located in the highly conserved region of p21 and may encode functionally distinct proteins. Although many epidemiological studies have been conducted to evaluate the association between the p21 Ser31Arg polymorphism and cancer risk, the findings remain conflicting. This meta-analysis with 33 077 cases and 45 013 controls from 44 published case-control studies showed that the variant homozygous 31Arg/Arg genotype was associated with an increased risk of numerous types of cancers in a random-effect model (homozygote comparison: OR = 1.17, 95% CI = 0.99 to 1.37, P = 0.0002 for the heterogeneity test; recessive model comparison: OR = 1.16, 95% CI = 1.01 to 1.33, P = 0.0001 for the heterogeneity test). Stratified analysis revealed that increased cancer risk associated with the 31Arg/Arg genotype remained significant in subgroups of colorectal cancer, estrogen-related cancer, Caucasians, population-based studies, studies with matching information or a larger sample size. Heterogeneity analysis showed that tumor type contributed to substantial between-study heterogeneity (recessive model comparison: Χ(2) = 21.83, df = 7, P = 0.003). The results from this large-sample sized meta-analysis suggest that the p21 31Arg/Arg genotype may serve as a potential marker for increased cancer risk.
Asian Continental Ancestry Group ; genetics ; Breast Neoplasms ; genetics ; Case-Control Studies ; Colorectal Neoplasms ; genetics ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; European Continental Ancestry Group ; genetics ; Gene Frequency ; Genetic Heterogeneity ; Genotype ; Humans ; Lung Neoplasms ; genetics ; Odds Ratio ; Polymorphism, Genetic ; Risk Factors

Objective:To analyze the impact of individual and regional level socioeconomic characteristics on the mental health of middle-aged and older adults based on data from the China Health and Retirement Longitudinal Study.Methods:This study was a cohort study. Using the data from the China Health and Retirement Longitudinal Study, subjects without depression were screened in the baseline survey, the depression status of the selected subjects was tracked and observed for seven years. Descriptive statistical analysis, multivariate logistic analysis, joint analysis were used to analyze the influence of factors such as gender, personal annual income, education level, urban and rural areas, and eastern, central, and western regions on the risk of depression among middle-aged and elderly people.Results:The 7-year follow-up results showed that the prevalence of depression symptoms in the study subjects was 42.24%; compared with men, women′s risk of developing depression symptoms was significantly increased ( OR=1.782); compared with junior college education and above, middle school (including technical secondary school), primary and lower education levels had a significantly increased risk of developing depression symptoms ( OR=1.476, 2.134); compared with annual income of more than 10 000 yuan, subjects with an annual income of 10 000 yuan or below had significantly increased risk of developing depression symptoms ( OR=1.251). At the same time, compared with the urban area, the risk of developing depression symptoms was significantly increased in the rural areas ( OR=1.389). Compared with the eastern area, the risk of developing depression symptoms was significantly higher in the central and western areas ( OR=1.342, 1.730). The joint analysis results showed that compared with high-income and high-education men, low-income low-education women, high-income low-education women, low-income middle-education women, and high-income middle-education women were at the top four odd ratios for developing depression symptoms ( OR=5.050, 3.662, 3.047, 2.641); compared with men in eastern cities, rural women in the west, rural women in the middle, women in the western cities, and rural women in the east ranked the first four odd ratios for developing depression symptoms ( OR=4.286, 3.216, 2.642, 2.158). Conclusion:Socioeconomic factors at the individual and regional levels have a significant impact on the risk of developing depressive symptoms in middle-aged and older adults, and mental health management of middle-aged and older adults with low socioeconomic status should be strengthened.

Objective: To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) . Methods: Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph⁺ ALL patients with p16 deletion. Results: Of 80 adult Ph⁺ ALL, the prevalence of p16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts (WBC≥30×10⁹/L) and CD20 expression. The incidence of complex chromosome abnormality in p16 gene deletion group was higher than that in non-deletion group, with alternations in chromosome 7, 8, 19 and der (22) more frequently observed. There was no difference occurred between patients with or without p16 gene deletion in complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs) . However, after three cycles of chemotherapy, the MMR and CMR rate in the p16 gene deletion group was lower than patients with wild-type p16 gene (P=0.034, P=0.036) . The p16 gene deletion patients showed no significant differences in MMR, CMR and relapse rate between Imatinib or Dasatinib plus chemotherapy (P>0.05) . Deletion of p16 gene was significantly associated with poor outcomes including worse overall survival (OS) (37.1% vs 54.1%, P=0.037) , lower disease free-survival (DFS) (12.4% vs 45.9%, P=0.026) , and increased cumulative incidence of relapse (P=0.033) . Among the 25 patients with p16 deletion, 14 underwent allo-HSCT and the median survival was 21 months, better than that of patients received chemotherapy alone (12 months) (P=0.030) . Conclusion This study indicated that deletion of p16 was associated with poor prognosis in adult Ph⁺ ALL, and the utility of second-generation TKI (Dasatinib) does not necessarily have an edge on efficacy over Imatinib, but allo-HSCT has the potential of elongating life expectancy. It is an important significance to define the status of p16 in Ph⁺ ALL for predicting prognosis and guiding therapy decision-making.

Objective:To investigate the diagnostic value of an intelligent assisted grading algorithm for nuclear cataract using anterior segment optical coherence tomography (AS-OCT) images.Methods:A diagnostic test study was conducted.AS-OCT image data were collected from 939 cases of 1 608 eyes of nuclear cataract patients at the Shanghai Tenth People's Hospital of Tongji University from November 2020 to September 2021.The data were obtained from the electronic case system and met the requirements for clinical reading clarity.Among them, there were 398 cases of 664 male eyes and 541 cases of 944 female eyes.The ages of the patients ranged from 18 to 94 years, with a mean age of (65.7±18.6) years.The AS-OCT images were labelled manually from one to six levels according to the Lens Opacities Classification System Ⅲ (LOCS Ⅲ grading system) by three experienced clinicians.This study proposed a global-local cataract grading algorithm based on multi-level ranking, which contains five basic binary classification global local network (GL-Net).Each GL-Net aggregates multi-scale information, including the cataract nucleus region and original image, for nuclear cataract grading.Based on ablation test and model comparison test, the model's performance was evaluated using accuracy, precision, sensitivity, F1 and Kappa, and all results were cross-validated by five-fold.This study adhered to the Declaration of Helsinjki and was approrved by Shanghai Tenth People's Hospital of Tongji University (No.21K216).Results:The model achieved the results with an accuracy of 87.81%, precision of 88.88%, sensitivity of 88.33%, F1 of 88.51%, and Kappa of 85.22% on the cataract dataset.The ablation experiments demonstrated that ResNet18 combining local and global features for multi-level ranking classification improved the accuracy, recall, specificity, F1, and Kappa metrics.Compared with ResNet34, VGG16, Ranking-CNN, MRF-Net models, the performance index of this model were improved.Conclusions:The deep learning-based AS-OCT nuclear cataract image multi-level ranking classification algorithm demonstrates high accuracy in grading cataracts.This algorithm may help ophthalmologists in improving the diagnostic accuracy and efficiency of nuclear cataract.

Objective:To evaluate a novel distraction reductor in the surgical treatment of unstable distal radius fractures with metaphyseal volar comminution.Methods:From January 2019 to December 2020, 27 patients with unstable distal radius fracture complicated with metaphyseal volar comminution were treated at Department of Orthopaedics, Zhoupu Hospital Affiliated to Shanghai University of Medicine & Health Sciences. They were 6 males and 21 females, with an age of (69.4±9.4) years. All fractures were unilateral and closed, involving the right side in 17 cases and the left side in 10 cases. All patients were treated by internal fixation with an anatomical locking plate through the volar approach and the novel distraction reductor was used to reduce the fracture ends. Regular imaging examinations were performed to evaluate the reduction, maintenance and union of fractures after surgery. One year after operation, the curative efficacy was assessed by evaluation of the range of wrist motion, Disabilities of the Arm, Shoulder and Hand (DASH) score, Gartland-Werley score and Bartra radiology score.Results:All the operations went on successfully with a duration of (92.3±8.9) min. All the incisions healed primarily. The follow-up time was (15.9±2.9) months. The radial height, palmar tilt, ulnar inclination and articular surface step-off immediately after operation [(11.23±1.51) mm, 12.10°±3.44°, 20.54°±3.44°, and (0.95±0.42) mm] were not significantly lost compared with those one year after operation [(11.22±1.55) mm, 12.07°±3.44°, 20.51°±3.33°, and (0.93±0.40) mm] (all P>0.05). One year after operation, the range of wrist motion was good with dorsiflexion of 59.7°±5.5°, palm flexion of 63.0°±9.1°, pronation of 66.5°±5.5°, supination of 61.2°±5.6°, radial deviation of 22.7°±4.8°, and ulnar deviation of 30.3°±6.1°; DASH score was 13.5±5.5; Bartra radiology score was 88.6±6.5, giving an excellent and good rate of 88.9% (24/27);Gartland-Werley score was 2.7±2.1, giving an excellent and good rate of 92.6% (25/27). Follow-ups observed no poor fracture healing, internal fixation failure, tendon or nerve injury or traumatic arthritis. Conclusion:In the surgical treatment of unstable distal radius fractures with metaphyseal volar comminution, the novel distraction reductor can lead to ideal reduction of displaced fractures and effectively correct the shortening caused by volar cortex comminution to achieve satisfactory functional effects in clinic.

Objective Based on intra-set correlation analysis, this paper deconstructs the clinical medical records of traditional Chinese medicine (TCM) Master ZHOU Zhongying in treating thyroid cancer, and analyzes the experience in “mechanism-syndrome-medicine-prescription” for thyroid cancer. Methods Through Medcase data processing platform, based on Frequent Pattern (FP)-Growth enhanced correlation analysis algorithm, the medical records of Professor ZHOU Zhongying for the treatment of thyroid cancer from June 1, 2001 to February 28, 2015 were analyzed within the set. Results This study involved 43 medical records, 43 patients, and 167 visits. After processing intra-set correlations, 28 groups of highly correlated symptoms, 21 groups of highly correlated tongue images, 10 groups of highly correlated pulse conditions, 28 groups of highly correlated pathogenesis, 34 groups of highly correlated herbs, and 26 groups of highly correlated western medicine diagnosis were selected. Professor ZHOU Zhongying treats thyroid cancer according to syndrome differentiation. Symptoms with more association rules included neck swelling, neck pain, cough, and dry mouth; tongue images with more association rules included dark purple tongue, dark red tongue, and fissured tongue; pulse conditions with more association rules were wiry pulse, thready pulse, small pulse, and slippery pulse; the pathogenesis with more association rules was phlegm and blood stasis, damp-heat accumulation, and impairment of both Qi and Yin; herbs with more association rules were Chaihu (Bupleuri Radix), Zeqi (Sun Euphoribiae Herb), and Tiandong (Asparagi Radix); western medicine diagnosis with more association rules included thyroid cancer, insomnia, and chronic gastritis. Conclusion Thyroid cancer mostly presents as deficiency in origin and excess in manifestations. The basic pathogenesis is phlegm and blood stasis, damp-heat accumulation, and impairment of both Qi and Yin, which are closely related to liver, kidney, and spleen. Professor ZHOU Zhongying adopts both attack and supplement approaches as the general treatment principle, with a strong emphasis on regulating Qi and relieving depression, eliminating phlegm and resolving stagnation, eliminating dampness and turbidity, clearing fire and destroying poison, moistening dryness and softening hard mass, invigorating Qi and nourishing Yin, and paying attention to nourishing liver and kidney, invigorating spleen and stomach, while protecting the heart and lungs.

Objective To investigate the residential radon concentration in typical areas of Hubei Province and assess the dose hazards of radon to human body. Methods According to geographical location, five cities including Wuhan, Enshi, Shiyan, Xianning and Daye were selected, and the stratified cluster sampling and monitoring were conducted in accordance with the residential building structure. From April to July, 2019, RSKS standard detectors were placed in the bedroom or living room of the tested families. After continuously sampling for three months, those detectors were returned back to the laboratory for test readings using Radosys system. Results A total of 651 detectors were deployed in 577 households of 70 communities, and 634 detectors were recovered. The recovery rate of detectors was 97.4%. The indoor residential radon concentration in Hubei Province showed a logarithmic normal distribution, with a median (25% quantile and 75% quantile) of 40.52 (29.13,64.74) Bq/m3 and an annual effective dose of 2.02 mSv. The indoor radon concentrations in Wuhan and Enshi were significantly higher than those in Shiyan, Xianning and Daye (P<0.05). The indoor radon concentrations in brick wood or civil structures were significantly higher than those in reinforced concrete structures (P<0.05), and indoor radon concentration in the first floor was significantly higher than those in other floors (P<0.05). The indoor radon concentrations after 2010 were significantly lower than those between 2001 and 2010 (P<0.05). Conclusion The number of households with indoor radon concentrations exceeding the national limit in newly-built buildings accounted for 10.1%; The indoor residential radon concentration levels of in Hubei Province were influenced by building structure, age and floor.

Objective: To explore the blood lead level and its relationship with behavior in school-age children from rural areas of Chongqing. Methods: A total of 697 students from grades 3 to 6 in the fall semester of 2014 from 14 rural townships in one district of Chongqing was selected by using the random cluster sampling method. Blood were sampled to analyze the lead level. Neurobehavioral tests were performed to determine their personal cognitive and memory ability. Questionnaires and physical examinations were administered to obtain the information of confounding factors. All students were divided into Q₁-Q₄ groups according to the quartile of their blood lead level. The relationship between the blood lead level and behavior was analyzed by multivariate logistic regression model and restricted spline regression model. Results: The mean age of 697 students was (10.07±1.36) years old, and the median (interquartile range) of their blood lead level was 44.31 (35.42) μg/L. Multivariate logistic regression model showed that after adjusting for age, gender, body mass index and maternal culture level, compared with Q₁ group, the OR (95%CI) values of high digit symbol substitution test (DSST) scores and high overall memory quotient (MQ) scores in Q₃ group were 1.65 (1.01-2.70) and 2.10 (1.21-3.62), and the OR (95%CI) value of high long term memory (LTM) scores in Q₄ group was 0.53 (0.31-0.92). The results of the restricted spline regression model showed that the dose-response curves between the blood lead level and MQ/LTM test scores were both parabolic (P<0.05). Conclusion The blood lead level of school-age children from rural areas of Chongqing is the same as that from other areas of China, but slightly higher than that from other areas of Chongqing. Children with higher blood lead level have poor long-term memory ability.