Objective: To investigate the epidemiological characteristics of varicella outbreaks in primary and middle schools, and to establish a risk predictive model, so as to provide scientific guidance for the prevention of varicella outbreaks in schools. Methods: Based on a nested case-control study, primary and middle schools in 4 districts of Shanghai (Yangpu District and Jingan District) and Hangzhou (Xiaoshan District and Linping District) from January to December 2023 were selected to observe the status of varicella outbreaks. Associated factors of varicella outbreaks were investigated and used for establishing the predictive model, which was evaluated by the Hosmer-Lemeshow(H-L) goodness of fit test, receiver operating characteristic (ROC) curve, Calibration curve, decision curve analysis (DCA). Results: A total of 98 varicella outbreaks were included, with 195 schools without varicella outbreaks during the same period as controls. Eight factors, including the availability of warm water in restroom, availability of hand soap in restroom, average class size, duration of student attendance at school per day, presence of a fulltime school doctor, hesitancy of the school principal towards varicella vaccination, and rates of first and second doses of varicella vaccination, were identified as potential factors for school varicella outbreaks, with statistically significant differences (χ2/Z=10.01, 20.49, 17.43, 9.74, 32.17, 6.60, 2.20, 3.39, P<0.05). The 8 variables above were employed to construct a risk predictive model, and Hosmer-Lemeshow goodness of fit test yielded a χ2 value of 5.863 (P>0.05); the area under the ROC curve (AUC) was 0.846 (95%CI=0.799-0.893); Calibration curve analysis indicated good consistency between predicted and actual values of the model. DCA demonstrated favorable predictive performance of the model over a wide range. Conclusions The predictive model for school varicella outbreaks demonstrates satisfactory accuracy and efficacy. It suggested to make good use of this prediction model and take relevant measures to reduce the risk of varicella transmission in schools.

Objective:To establish a prediction model of risk factors for early Q-T interval prolongation after acute myocardial infarction (AMI), which helps prevent and reduce the occurrence of acute malignant events.Methods:This is a case-control study. A total of 100 patients with Q-T interval prolongation after AMI who received treatment at Heilongjiang Provincial Hospital from January 2018 to December 2022 were included in this study. An additional 100 patients without Q-T interval prolongation after AMI who concurrently received treatment in the same hospital were also included in this study. Two model groups, including model group 1 (with Q-T interval prolongation, n = 50) and model group 2 (without Q-T interval prolongation, n = 50), and two test groups, including test group 1 (with Q-T interval prolongation, n = 50) and test group 2 (without Q-T interval prolongation, n = 50), were designated. Logistic regression analysis was performed to construct a prediction model of risk factors for Q-T interval prolongation. The area under the receiver operating characteristic curve was determined to evaluate the prediction model. The value of the prediction model was validated in the test groups. Results:Multivariate logistic regression showed that female gender ( OR = 2.307, 95% CI: 0.09-0.91, P = 0.041) and heart failure ( OR = 3.087, 95% CI: 1.15-8.27, P = 0.025) were independent risk factors for early Q-T interval prolongation after AMI. The area under the receiver operating characteristic curve of the prediction model was 0.770, with a sensitivity of 84.0%, a specificity of 66.0%, the Jordan index of 0.44, and the corresponding optimal critical value of 0.43. This indicates good fit of the model. Conclusion:Female gender and heart failure are independent risk factors for early Q-T interval prolongation after AMI. The model constructed based on the above-mentioned risk factors fits well and has a high predictive value, which helps reduce the occurrence of early Q-T interval prolongation after AMI.

Objective To propose a distribution feature extraction algorithm based on wavelet packet coefficients to reconstruct the signal energy sequence for effectively identifying the pathological features of heart sounds,thereby realizing the early screening of heart diseases.Methods The original heart sound signal was decomposed into 10 layers using wavelet packet decomposition algorithm.After obtaining the wavelet packet coefficients of each layer,each coefficient was reconstructed,and the energy of the reconstructed signal was calculated and arranged in the original order to form the energy sequence.The distribution characteristics of the energy sequence of the reconstructed signals at each layer were analyzed,and distribution features were taken as classification features.Support vector machine,K-nearest neighbor,and decision tree were used to classify and recognize normal heart sounds and the heart sound signals of various diseases.Results The combination of the distribution features of the reconstructed signal energy sequence and decision tree classifier had an accuracy of 93.6%for classifying 5 types of heart sounds on the public dataset,and the accuracy was 95.6%for identifying normal heart sounds and hypertrophic cardiomyopathy heart sounds.Conclusion The proposed algorithm can extract the effective pathological information of abnormal heart sounds,providing a reference for clinical cardiac auscultation.

The construction of clinical research management system in public hospitals is an important platform for China's clinical research workers to achieve new products conversion and application.At present,China have basically realized the informatization of clinical trial management process and scientific research project,improved the efficiency and quality of scientific research management,but there is still a large distance from the requirements of digital management platform.The core problem is that there is no unified standard for clinical data collection,disjointed management of the whole process,and backward communication and collaboration mode.The establishment of a standardized disease database has become an effective means to achieve standardized clinical data,and it is the basis for opening up the clogging point of the whole process management and realizing multi-department data sharing.

Objective To explore the relationship between alterations of neural network plasticity and spatial learning and memory functions in mouse models with depression-like behaviors.Methods C57Thy1-YFP/GAD67-GFP mice were randomized into control group(with no treatment)and chronic unpredictable mild stress(CUMS)group(n=15)subjected to CUMS for 8 weeks.Depression-like behaviors of the mice were assessed using sucrose preference test,open field test,and forced swimming test,and their spatial learning and memory abilities were evaluated using Morris water maze test.The changes in the firing patterns of different neuronal subtypes were detected in the central nucleus of the amygdala(CeA)and the prelimbic cortex(PrL)using whole-cell patch-clamp technique.Results Compared with the control mice,CUMS mice showed significantly decreased sucrose preference,total distance moved,number of grid-crossings,entries into the central area,and time spent in the central area in the open field test(P<0.01).In the forced swimming test,CUMS mice exhibited obviously shortened time of struggling,swimming,and climbing with increased immobility time.In Morris water maze test,CUMS mice showed significantly increased escape latency and path length,decreased percentage of distance and swimming time within the target quadrant,and increased first entry latency into the target zone and swimming time within the opposite quadrant.Exposure to CUMS resulted in significantly enhanced energy barrier and increased absolute refractory period and inter-spike interval of glutamatergic neurons in the CeA and GABAergic neurons in the PrL,while the opposite changes were observed in GABAergic neurons in the CeA and glutamatergic neurons in the PrL.Conclusion CUMS-induced depression may lead to plastic changes in the excitatory and inhibitory neuronal networks within the CeA and PrL to cause impairment of spatial learning and memory abilities in mice.

Objective To explore the relationship between alterations of neural network plasticity and spatial learning and memory functions in mouse models with depression-like behaviors.Methods C57Thy1-YFP/GAD67-GFP mice were randomized into control group(with no treatment)and chronic unpredictable mild stress(CUMS)group(n=15)subjected to CUMS for 8 weeks.Depression-like behaviors of the mice were assessed using sucrose preference test,open field test,and forced swimming test,and their spatial learning and memory abilities were evaluated using Morris water maze test.The changes in the firing patterns of different neuronal subtypes were detected in the central nucleus of the amygdala(CeA)and the prelimbic cortex(PrL)using whole-cell patch-clamp technique.Results Compared with the control mice,CUMS mice showed significantly decreased sucrose preference,total distance moved,number of grid-crossings,entries into the central area,and time spent in the central area in the open field test(P<0.01).In the forced swimming test,CUMS mice exhibited obviously shortened time of struggling,swimming,and climbing with increased immobility time.In Morris water maze test,CUMS mice showed significantly increased escape latency and path length,decreased percentage of distance and swimming time within the target quadrant,and increased first entry latency into the target zone and swimming time within the opposite quadrant.Exposure to CUMS resulted in significantly enhanced energy barrier and increased absolute refractory period and inter-spike interval of glutamatergic neurons in the CeA and GABAergic neurons in the PrL,while the opposite changes were observed in GABAergic neurons in the CeA and glutamatergic neurons in the PrL.Conclusion CUMS-induced depression may lead to plastic changes in the excitatory and inhibitory neuronal networks within the CeA and PrL to cause impairment of spatial learning and memory abilities in mice.

L-asparaginase (L-ASN) is widely applied in the treatment of malignant tumor and low-acrylamide food production, however, the low expression level hampers its application. Heterologous expression is an effective strategy to increase the expression level of target enzymes, and Bacillus is generally used as the host for efficient production of enzymes. In this study, the expression level of L-asparaginase in Bacillus was enhanced through optimization of expression element and host. Firstly, five signal peptides (SP_SacC, SP_AmyL, SP_AprE, SP_YwbN and SP_WapA) were screened, among which SP_SacC showed the best performance, reaching an activity of 157.61 U/mL. Subsequently, four strong promoters (P43, P_ykzA-P43, P_Ubay and P_bacA) from Bacillus were screened, and tandem promoter P_ykzA-P43 showed the highest yield of L-asparaginase, which was 52.94% higher than that of control strain. Finally, three Bacillus expression hosts (B. licheniformis Δ0F3 and BL10, B. subtilis WB800) were investigated, and the maximum L-asparaginase activity, 438.3 U/mL, was reached by B. licheniformis BL10, which was an 81.83% increase compared with that of the control. This is also the highest level of L-asparaginase in shake flask reported to date. Taken together, this study constructed a B. licheniformis strain BL10/P_ykzA-P43-SP_SacC-ansZ capable of efficiently producing L-asparaginase, which laid the foundation for industrial production of L-asparaginase.
Bacillus licheniformis/metabolism* ; Asparaginase/genetics* ; Bacillus/genetics* ; Protein Sorting Signals ; Promoter Regions, Genetic/genetics* ; Bacillus subtilis/genetics* ; Bacterial Proteins

[摘 要] 目的：重新评价卡瑞利珠单抗联合阿帕替尼治疗原发性肝癌（PHC）的有效性和安全性。方法：回顾性收集2019年1月至2021年5月在安徽医科大学附属第一医院确诊的PHC患者的临床资料。所有患者均接受卡瑞利珠单抗200 mg q3w联合阿帕替尼250 mg qd×21 d治疗。应用卡方检验进行基线特征比较，采用Kaplan-Meier法进行生存分析，从中估计中位总生存期（OS），然后采用Log-Rank检验进行比较；采用单因素Cox回归分析预测影响OS的因素。结果：本研究共纳入43例PHC患者，一线治疗患者的客观缓解率（ORR）为23.3%（7/30），二线及以上治疗患者的ORR为15.4%（2/13）。两组患者的疾病控制率（DCR）分别为83.3%（25/30）和61.5%（8/13），中位无进展生存期（PFS）分别为5.0个月（95% CI 3.2，6.8）和4.0个月（95% CI 1.7，6.3）（P=0.514），中位OS分别为13.0个月（95% CI 11.2，14.8）和9.0个月（95% CI 2.8，15.2）（P=0.179）。在43例患者中，33例（76.7%）存在3级或以上的治疗相关不良反应（AE）；最常见的AE为血小板计数下降（14.0%）、高血压（9.3%）和蛋白尿（9.3%）。Cox单因素回归分析显示，Child-Pugh分级是影响PHC患者预后的独立危险因素[HR=0.324，95% CI （0.146，0.716），P<0.05]。结论：卡瑞利珠单抗联合阿帕替尼可显著改善PHC患者的OS、ORR和DCR，AE可控。

Objective To study mechanical properties of the anisotropy for pig trachea and main bronchi, and determine the constitutive model of trachea deformation by finite element numerical simulation. Methods The pig tracheas were collected and cut through in their axial directions and expanded into two-dimensional planes. Then, by setting the length direction of the trachea aortas as 0°, each planar trachea was anticlockwisely cut into 6 samples with orientation of 30°,60°,90°,120°,150° and 180°, respectively. Uniaxial tensile tests were applied on the specimen in 6 angular directions by using the electronic universal test machine, to obtain stress and strain of the specimen in different directions. Nonlinear fitting to the experimental data was performed by using the Mooney-Rivilin hyperelastic model, in order to obtain the material characteristic parameters. Finite element models of the trachea and the main bronchi were established, and tensile numerical simulation was carried out.Results Samples at different angles showed different stress-strain curves. In the trachea, the stresses of samples with angle of 30°, 120° and 150° were in the range of 1.0-1.5 MPa, the stresses of samples with angle of 60° and 90° were in the range of 0.5-1.0 MPa, and the stresses of samples with angle of 180° were in the range of 2.5-3.0 MPa. In the main bronchi, the stresses of samples with angle of 30°, 120° and 150° were in the range of 0.8-1.0 MPa, the stresses of samples with angle of 90° and 180° were in the range of 1.4-1.8 MPa, and the stresses of samples with angle of 120° were in the range of 0.4-0.6 MPa. There was an obvious difference between the trachea and the main bronchi. The finite element simulation verified that the Mooney-Rivilin constitutive model was suitable for describing small deformation behavior of the trachea. Conclusions The pig trachea exhibits strong anisotropy. Meanwhile, the Mooney-Rivilin model can characterize small tracheal deformations. The results provide theoretical references for tracheal resection and reconstruction in clinical treatment and intervention with surgical instruments such as bronchoscopy.

Platinum anti-tumor drugs are currently the most widely used first-line chemotherapeutic drugs in clinical practice, and their curative effects are remarkable. However, the problems of platinum drug resistance in non-small cell lung cancer, breast cancer, ovarian cancer and others seriously limit effectiveness and clinical application of platinum drugs. The occurrence of platinum drug resistance is caused by many factors. At present, the resistance mechanism of platinum drugs mainly includes the following aspects: decreasing the accumulation of platinum in cells, increasing the inactivation of platinum in cells, repairing DNA damage and tumor cell apoptosis inactivation. This article reviews the drug resistance mechanism and coping strategy of platinum anti-tumor drugs, providing ideas for the development of platinum anti-tumor drugs and references for overcoming clinical platinum drug resistance.